Regulatory Expectations for Cell and Gene Therapies

Ramjay S. Vatsan, Ph.D., CQAGene Therapy Team Leader

Division of Cellular and Gene TherapiesOffice of Tissue and Advanced Therapies

Center for Biologics Evaluation and Research/FDA

4th PQRI/FDA Conference on Advancing Product Quality: Patient-Centric Product Design, Drug Development, and Manufacturing

April 9-11, 2019

www.fda.gov

Outline

• Introduction• CMC expectations for early-stage product

development• CMC expectations for late-stage product

development • Accelerating product development - FDA

initiatives• Summary - Cautious Optimism in Gene Therapy

2www.fda.gov

FDA Approved Oncolytic and GT Products

• Imlygic (Amgen- HSV- Approved 2015)– Genetically modified oncolytic viral therapy – for the local treatment of unresectable cutaneous, subcutaneous, and

nodal lesions in patients with melanoma recurrent after initial surgery.

• Luxturna (Spark- AAV-GT Approved 2017)– For the treatment of patients with confirmed biallelic RPE65 mutation-

associated retinal dystrophy.

• Kymriah (Novartis- Lentivirus- Approved 2017)– CD19-directed genetically modified autologous T cell immunotherapy – For up to 25 year old with acute lymphoblastic leukemia (ALL)

• Yescarta (Kite- Retrovirus- Approved 2017)– CD19-directed genetically modified autologous T cell immunotherapy– For adult patients with relapsed or refractory large B-cell lymphoma

(DLBCL) 3www.fda.gov

Rapid Growth in Annual GT IND Applications

4www.fda.gov

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1985 1990 1995 2000 2005 2010 2015 2020 2025

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310*

Years

Num

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f Gen

e Th

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Imlygic, Sept 2015

Yescarta, Oct 2017Luxturna, Dec 2017

Kymriah, Aug 2017

* Projected based on 108 INDs received till April 2019

206

5

Bacteria(4%)

Plasmid(31%)

Adenovirus(16%)

Other (4%)

Pox Virus(9%)

Retrovirus(21%)

Lentivirus(8%)

AAV (5%)

HSV(2%)

2014

AAV(12%)

Other (2%)

Retrovirus(17%)

Lentivirus(17%)

Plasmid(19%)

Bacteria(5%)

Pox Virus(9%) HSV

(5%)

2018

Adenovirus(14%)

Gene Therapy Vectors Rapid growth in AAV and Lentivirus as vectors of choice in GT

CAR T cell Targets 111 active CAR T cell investigations in OTAT as of 6/30/18

CD19:• Expressed on B-cells• Targets hematologic cancersBCMA:• B-cell maturation Antigen• Expressed on malignant plasma cells

32% SolidCancers 68%

HematologicCancers

44% CD19-directedBCMA

www.fda.gov6

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birams_searchsubmissions

This document contains Sensitive But Unclassified (SBU) information and is intended FOR OFFICIAL USE ONLY. The contents are not intended for public release. Do not disseminate, distribute, or share with persons not authorized to receive such information. All sensitive data must be properly labeled prior to dissemination to authorized persons.

TypeSub IdSponsorContactTitletargetProposed UseProductOfficeIRA StatusIRA Status DateSubmission DateFDA Receipt DateCenter Receipt Dateyear submittedIRA Comments

1IND13266Memorial Sloan-Kettering Cancer CenterHo MD PhD, AlanAutologous CD3+ T-cells Transduced with Retroviral Vector (SFG-1928z, MSKCC) Expressing CD19 Chimeric Antigen Receptor;; Cultured with Interleukin-2CD19Treatment of purine analogue refractory chronic Lymphocytic LeukemiaAldesleukin [Proleukin]; Autologous CD3+ T-cells Transduced with CD19 chimeric antigen receptor gene (Retroviral Vector SFG-1928z, MSKCC); Cultured with Interleukin-2OTATPARTIAL HOLD30-Nov-1511-Jan-0716-Jan-0716-Jan-0720077/1/2015 - Authorized Contacts: Dr. Alan Ho; Richard Ellis (TEL: 646-735-8044; FAX: 646-888-0940; Email: ellisr@mskcc.org)

1IND13296Center for Cell and Gene TherapyHeslop MD, Helen EAutologous PBMC Cultured w/IL-2 and OKT3; Transduced w/Retroviral Vector (CD19-CAR) Expressing CD19 Chimeric Antigen Receptor Gene; and Autologous PBMC Cultured w/IL-2 and OKT3; Transduced w/Retroviral Vector (CD19-CD28-CAR) Expressing CD19-CD28 Chimeric Antigen Receptor GeneCD19Treatment of B-Cell non Hodgkin's lymphoma and Chronic lymphocytic leukemiaAldesleukin [Proleukin]; MoAb, OKT3, Murine, to CD3+ [Orthoclone OKT3]; Peripheral Blood Mononuclear Cells (Autologous) Transduced with CD19 Chimeric Antigen Receptor Gene (Retroviral Vector CD19-CAR); Peripheral Blood Mononuclear Cells (Autologous) Transduced with CD19-CD28 Chimeric Antigen Receptor Gene (Retroviral Vector CD19-CD28-CAR)OTATACTIVE9-Mar-075-Feb-079-Feb-079-Feb-0720074/29/2014 - Secure email authorized. Authorized Contacts: Helen Heslop, MD (Phone: 832-824-4662; Fax: 832-825-4203;Email: hheslop@bcm.edu); Malcolm Brenner, MD (Phone: 832-824-4661; Fax: 832-825-4203; Email: mbrenner@bcm.edu); Carlos Ramos, MD (Phone: 832-824-4817; Fax: 832-825-4203; Email: caramos@bcm.edu); Bambi Grilley (Phone: 832-824-3893; Fax: 832-825-4203; Email: grilley@bcm.edu)

voidIND13313Center for Cell and Gene TherapyHeslop MD, Helen ENEW IND 1571 : T Lymphocytes tranduced with a chimeric antigen receptor targeting CD19CD19OCTGTVOIDED5-Mar-0727-Feb-075-Mar-075-Mar-07IND Voided 03/09/2007, this is an Amendment to IND 13296.

withdrawnIND13831Rosenberg MD PhD, Steven ARosenberg MD PhD, Steven AAutologous Peripheral Blood Lymphocytes Cultured with OKT3 and Interleukin-2, Transduced with Retroviral Vector (PG13-4D5-D12, IU VPF) Expressing Her2/neu Chimeric Antigen Receptor Gene; and Interleukin-2Her2Treatment of metastatic cancers that overexpress Her2Interleukin-2, IL-2, Aldesleukin; MoAb, OKT3, Murine, to CD3+ [Orthoclone OKT3]; peripheral blood lymphocytes (autologous) transduced with Her2/neu chimeric antigen receptor gene (retroviral vector, PG13-4D5-D12)OCTGTWITHDRAWN10-Nov-105-Sep-089-Sep-089-Sep-08

1IND13871Center for Cancer ResearchDahut MD, WilliamAutologous Peripheral Blood Lymphocytes Cultured with OKT3 and Interleukin-2; Transduced with Retroviral Vector PG13-CD19-H3, NCI) Expressing Anti-CD19 Chimeric Antigen Receptor Gene; and Interleukin-2CD19Treatment of advanced B-cell malignanciesCliniMACS CD19 reagent system; Interleukin-2; Aldesleukin; MoAb, OKT3, Murine, to CD3+ [Orthoclone OKT3]; Peripheral Blood Lymphocytes, Autologous, Transduced with Anti-CD19 Chimeric Antigen Receptor Gene (Retroviral Vector PG13-CD19-H3)OTATACTIVE28-Feb-1330-Oct-083-Nov-083-Nov-08200812/5/2012-Non-secure email authorized. 5/19/16 Update Authorized Contacts: Include on all emails (nciprotocolsupportoffice@mail.nih.gov);William Dahut, MD (P: 301-435-8183; dahutw@mail.nih.gov) Mary Ann Toomey (P:301-435-7507; toomeym@mail.nih.gov); Steven A Rosenberg, MD, PhD (P:301-435-7507; F: 301-435-7208; EMAIL:sar@mail.nih.gov); Nicole Grant (PHONE: 301-272-0476;grantn@mail.nih.gov).

1IND13902Center for Cell and Gene TherapyBrenner MD PhD, Malcolm KAutologous PBL Cultured with OKT3, Transduced with Retroviral Vector (SFG.CD19CAR-28zeta) Expressing CD19 Chimeric Antigen Receptor Gene; and Autologous, EBV Specific CTL Cultured with IL-2, Transduced with Retroviral Vector (SFG.CD19CARzeta) Expressing CD19 Chimeric Antigen Receptor GeneCD19Treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemiaAutologous PBL Transduced with Retroviral Vector (SFG.CD19CAR-28zeta) Expressing CD19 Chimeric Antigen Receptor Gene; Autologous, EBV Specific CTL Transduced with Retroviral Vector (SFG.CD19CARzeta) Expressing CD19 Chimeric Antigen Receptor GeneOTATACTIVE9-Jan-096-Nov-0810-Dec-0810-Dec-0820088/27/2012 Authorized Contacts: Helen E. Heslop, MD; Malcolm Brenner, MD, PhD; Bambi Grilley, RPh

1IND13958Center for Cell and Gene TherapyBrenner MD PhD, Malcolm KAutologous Peripheral Blood Mononuclear Cells co-cultured with Autologous Dendritic Cells Transduced with Adenovirus Vector (Ad5f35CMVpp65, CCGT) Expressing CMVpp65 then Expanded with LCL Transduced with Adenovirus Vector (Ad5f35CMVpp6, CCGT) Expressing CMVpp65; Transduced with Retroviral Vector (SFG.CD19CAR28) Expressing CD19 Chimeric Antigen Receptor GeneCD19Treatment of relapsed high-risk B-cell Acute Lymphoblastic Leukemia post Hemopoietic Stem Cell TransplantAutologous Peripheral Blood Mononuclear Cells co-cultured with Autologous Dendritic Cells Transduced with Adenovirus Vector (Ad5f35CMVpp65, CCGT) Expressing CMV; LCL Transduced with Adenovirus Vector (Ad5f35CMVpp6, CCGT) Expressing CMVpp65; Transduced with Retroviral Vector (SFG.CD19CAR28) Expressing CD19OTATACTIVE14-Mar-095-Feb-0912-Feb-0912-Feb-0920098/27/2012 Authorized Contacts: Helen E. Heslop, MD; Malcolm Brenner, MD, PhD; Bambi Grilley, RPh. Sponsor authorized email communication in cover letter of IND submission (mbrenner@bcm.edu). Alt contacts: Helen Heslop (hheslop@bcm.edu), Catherine Bollard (cbollard@bcm.edu) and Bambi Grilley (grilley@bcm.edu)

1IND13960Univ of PennsylvaniaMeagher MD, Emma AAutologous T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen ReceptorCD19Treatment of refractory CD19+ leukemia and lymphoma ADDITIONAL CONTACTS: Shelly Fehr (215-662-4639; sfehr@exchange.upenn.edu)Autologous T Cells Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen ReceptorOTATACTIVE1-Feb-1717-Feb-0918-Feb-0918-Feb-092009Amendment 254: Emma Meagher: emma@upenn.edu, Carl June: cjune@upenn.edu, Elizabeth Hexner: Elizabeth.Hexner@uphs.upenn.edu, Katherine Marcucci: kmarcu@upenn.edu, Deanna DiDonato: deannad@upenn.edu, Praharshkumar Shah: prahp@upenn.edu, Shelly Fehr: sfehr@upenn.edu

1IND13965Center for Cell and Gene TherapyBrenner MD PhD, Malcolm KAutologous Peripheral Blood Mononuclear Cells Cultured with OKT3 and Interleukin-2 and Transduced with Retroviral Vector (pG13.SFG.CAR-K, CAGT VPF) Expressing Kappa-Light Chain Chimeric Antigen Receptor GeneCD19Treatment of non-Hodgkin lympoma and chronic lymphocytic leukemiaAutologous Peripheral Blood Mononuclear Cells Transduced with Retroviral Vector (pG13.SFG.CAR-K, CAGT VPF)OTATACTIVE27-Mar-0923-Feb-0925-Feb-0925-Feb-0920098/27/2012 Authorized Contacts: Helen E. Heslop, MD; Malcolm Brenner, MD, PhD; Bambi Grilley, RPh. Sponsor authorized email communication in cover letter of IND submission (mbrenner@bcm.edu). Alt contacts: Helen Heslop (hheslop@bcm.edu), and Bambi Grilley (grilley@bcm.edu)

1IND14036Center for Cell and Gene TherapyGottschalk MD, StephenAutologous EBV-specific CTL Transduced with Retroviral Vectors (SFG.TGFbetaR11deltacyt) Expressing Dominant Negative TGFbeta Receptor II Gene and (SFG.FP5.CD28.zeta) Expressing the HER2 Chimeric Antigen Receptor Gene; Expanded with Interleukin-2Her2Treatment of HER2 positive lung cancerAutologous EBV-specific CTL Transduced with Retroviral Vector (SFG.TGFbetaR11deltacyt) Expressing Dominant Negative TGFbeta Receptor II Gene; Autologous EBV-specific CTL Transduced with Retroviral Vector SFG.FP5.CD28.zeta) Expressing the HER2 Chimeric Antigen Receptor GeneOTATACTIVE25-Sep-0929-Apr-091-May-091-May-0920098/27/2012 Authorized Contacts: Helen E. Heslop, MD;; Malcolm Brenner, MD, PhD; Bambi Grilley, RPh; Stephen Gottschalk, MD.

1IND14050Center for Cell and Gene TherapyHeslop MD, Helen EAutologous EBV-specific CTL Transduced with Retroviral Vectors (HER2.CAR.CD28.zeta) Expressing the HER2 Chimeric Antigen Receptor GeneHer2treatment of advanced HER2 positive osteosarcomaAutologous EBV-specific CTL Transduced with Retroviral Vectors (HER2.CAR.CD28.zeta) Expressing the HER2 Chimeric Antigen Receptor GeneOTATACTIVE8-Jan-1021-May-0922-May-0922-May-092009Secure email established for @bcm.edu. 8/27/2012 Authorized Contacts: Helen Heslop, MD (832-824-4671; EMAIL: hheslop@bcm.edu); Malcolm Brenner, MD (PHONE: 832-824-4671; FAX: 832-825-4203; EMAIL: mbrenner@bcm.edu); Bambi Grilley, RPh (PHONE: 832-824-3893; EMAIL: grilley@bcm.edu); Stephen Gottschalk, MD.

1IND14172Center for Cancer ResearchDahut MD, WilliamAllogeneic Pheripheral Blood Lymphocytes Transduced with Retroviral Vector PG13-CD19-H3 Expressing anti-CD19 Chimeric Antigen Receptor GeneCD19Treatment of recurrent or persistent B-Cell malignancies after allogeneic stem cell transplantationAldesleukin [Proleukin]; MoAb, OKT3, Murine to CD3+[Orthoclone OKT3]/MoAb, Murine to CD28+, Magnetic Bead; Peripheral Blood Lymphocytes, Autologous, Transduced with Anti-CD19 Chimeric Antigen Receptor Gene (Retroviral Vector PG13-CD19-H3)OTATPARTIAL HOLD11-Aug-1530-Sep-091-Oct-091-Oct-09200912/28/2012 Authorization to communicate via non-secure email. 6/10/2016 Update Authorized Contacts: INCLUDE ON ALL EMAILS (nciprotocolsupportoffice@mail.nih.gov); William Dahut MD (dahutw@mail.nih.gov); Ronald Gress, MD (PHONE: 301-496-1791; FAX: 301-480-4354; EMAIL: gressr@mail.nih.gov); Nicole Grant (PHONE: 301-272-0476;grantn@mail.nih.gov).

1IND14193Univ of TexasBuzdar MD, AmanAutologous CD19 Specific T cells Transduced with DNA Plasmid Vectors (Sleeping Beauty System) Expressing Chimeric Antigen Receptor; Co-cultured with Gamma-irradiated K562 Tumor Cell Line Transduced with Lentiviral Vectors; with or without Interleukin-2CD19Treatment for B-lymphoid malignancy relapse following autologous HSCTAutologous CD19 Specific T cells Derived from PBMC Transduced with Sleeping Beauty Plasmid DNA; CliniMACS CD56 Reagent System; Interleukin-2 (Proleukin)OTATACTIVE24-May-1013-Oct-0914-Oct-0914-Oct-0920099/9/2013 Updated Authorized Contacts: Stell Tsai (Ph: 713-563-5464 Email: swtsai@mdanderson.org), Sean O'Connor (Ph: 713-563-1863 Email: soconnor@mdanserson.org), Felicia Nica (Ph: 713-792-8163 Email: alinan@mdanderson.org), Bridget Chapital (Ph: 713-563-0064 Email: bochapital@mdanderson.org), Eliana Turk (Ph: 713-745-3467 Email: etturk@mdanderson.org), Aman Buzdar (Ph: 713-745-7139 Email: abuzdar@mdanderson.org)

1IND14403Center for Cell and Gene TherapyHeslop MD, Helen EAutologous Peripheral Blood Mononuclear Cells co-cultured with Autologous Dendritic Cells Transduced with Adenovirus Vector (Ad5f35CMVpp65, CCGT) Expressing CMVpp65 then Expanded with LCL Transduced with Adenovirus Vector (Ad5f35CMVpp6, CCGT) Expressing CMVpp65; Autologous EBV-specific CTL Transduced with Retroviral Vector (HER2.CAR.CD28.zeta) Expressing the HER2 Chimeric Antigen Receptor GeneHer2Treatment of Glioblastoma MultiformePeripheral Blood Mononuclear Cells, Autologous,; Dendritic Cells, Autologous, Transduced with CMVpp65 Gene (Adenovirus Vector, Ad5f35CMVpp65); EBV-specific CTL, Autologous Transduced with HER2 Chimeric Antigen Receptor Gene (Retroviral Vector, HER2.CAR.CD28.zeta); LCL Transduced with CMVpp65 (Adenovirus Vector Ad5f35CMVpp6)OTATACTIVE15-Jul-101-Jun-1015-Jun-1015-Jun-1020108/27/2012 Authorized Contacts: Helen E. Heslop, MD; Malcolm Brenner, MD, PhD; Bambi Grilley, RPh; Stephen Gottschalk, MD. 7/1/2010 The sponsor authorized the use of non-secure email in amendment #1 with the following people: Nabil Ahmed, MD (nmahmend@txccc.org) 832-824-4611 Stephen Gottschalk, MD (smg@bcm.tmc.edu ) 832-824-4179 Malcolm Brenner, MD (mbrenner@bcm.edu ) 832-824-4671 Helen Heslop, MD (hheslop@bcm.edu ) 832-824-4671 Bambi Grilley, RPh (grilley@bcm.edu ) 832-824-3893

1IND14440Center for Cancer ResearchDahut MD, WilliamAutologous CD8+ Enriched PBL Cultured with OKT3 and IL2, Transduced with Retroviral Vector PG13-KDR1121-hCD828 BBZ (D11) Expressing Chimeric Antigen Receptor GeneVEGFR-2Treatment of Metastatic CancerCliniMACS CD8 Microbeads; Interleukin-2, IL-2, Aldesleukin; MoAb, Murine, to CD8+, for Cell Selection; MoAb, OKT3, Murine, to CD3+ [Orthoclone OKT3]; PBL, Autologous CD8+ Enriched Transduced with Chimeric Antigen Receptor Gene (Retroviral Vector PG13-KDR1121-hCD828 BBZ (D11)OTATWITHDRAWN22-Feb-1714-Jul-1016-Jul-1016-Jul-10201012/5/2012-Non-secure email authorized. Authorized Contacts: Mary Ann Toomey, RN, Surgery Branch Protocol Support Office (EMAIL: toomeym@mail.nih.gov;PHONE:301-435-7507); Steven A Rosenberg, MD, PhD (PHONE:301-435-7507; FAX: 301-435-7208; EMAIL:sar@mail.nih.gov)

1IND14476Carl JuneAutologous CD4+ and CD8+ T cells Transduced with Lentiviral Vector Expressing Chimeric Anti-Mesothelinmesotreatment of ovarian cancer13-Aug-102010

1IND14506CAGTAUTOLOGOUS EPSTTEIN BARR VIRUS SPECIFIC CYTOTOXIC T LYMPHOCYTES TRANSDUCED WITH RETROVIRAL VECTOR SFG.CD30.CD28.ZETA EXPRESSING CD30 SPECIFIC CAR; CULTURED WITH IL2 AND AUTOLOGOUS EPSTEIN BARR VIRUS + LYMPHOBLASTOID CELL LINECD19Hodgkin’s L./Non Hodgkin’s L.10-Aug-102010

1IND14577Univ of TexasBuzdar MD, AmanImmunoreceptor; Administered Intratumorally of IntravenouslyCD19Treatment of B-lineage lymphoid malignanciesAllogeneic CD19 Specific T cells Derived from PBMC Transduced with Sleeping Beauty Plasmid DNA; CliniMACS CD56 Reagent System; Interleukin-2 (Proleukin)OTATACTIVE31-Dec-1030-Nov-101-Dec-101-Dec-1020109/17/2013-Non-secure email authorized. Authorized Contacts: Stell Tsai (Ph: 713-563-5464 Email: swtsai@mdanderson.org), Sean O'Connor (Ph: 713-563-1863 Email: soconnor@mdanserson.org), Felicia Nica (Ph: 713-792-8163 Email: alinan@mdanderson.org), Bridget Chapital (Ph: 713-563-0064 Email: bochapital@mdanderson.org), Eliana Turk (Ph: 713-745-3467 Email: etturk@mdanderson.org), Aman Buzdar (Ph: 713-745-7139 Email: abuzdar@mdanderson.org)

1IND14645City of HopeAutologous CD8+ T cells; CD62 Enriched (Anti-CD62L-Biotin, City of Hope) ;CD3/CD28 Activated;CD19(CD19) non-Hodgkin's Lymphoma22-Feb-112011

withdrawnIND14657MYERS MD, G DOUGLASALLOGENEIC EBV, CMV, AND ADENOVIRUS SPECIFIC CTLS TRANSDUCED WITH RETROVIRAL VECTOR (SFG14G2A.ZETA) EXPRESSING GD-2 CAR ; AND IL-2gd-2

1IND14688LINEBERGER COMPREHENSIVE CANCER CENTERAUTOLOGOUS ACTIVATED T LYMPHOCYTES TRANSDUCED WITH RETROVIRAL VECTOR (SFG.CD30.CD28.ZETA) EXPRESSING CD30 SPECIFIC CARcd30Hodgkin`s Lymphoma and Non Hodgkin`s Lymphoma7-Apr-112011

1IND14739Univ of TexasBuzdar MD, AmanTransduced with Lentiviral Vector (rCD19Rop-epHIV7, City of Hope);Cultured with Interleukin-2 andCD19Treatment of B-Lineage Lymphoid Malignancies after Umbilical Cord Blood TransplantationCliniMACS CD56 Reagent System; Interleukin-2, IL-2, Aldesleukin; Interleukin-21; K-562 Cell Line Transduced with CD19 gene (Lentiviral Vector); T Cells, Allogeneic, Transfected with CD19 Specific Chimeric Antigen Receptor (Sleeping Beauty Plasmid DNA)OTATACTIVE28-Sep-1126-May-111-Jun-111-Jun-1120116/6/2011 - Non-secure email authorized. 10/21/2013 Update Authorized Contacts: Stella Tsai (Ph: 713-563-5464 Email: swtsai@mdanderson.org), Sean O'Connor (Ph: 713-563-1863 Email: soconnor@mdanserson.org), Felicia Nica (Ph: 713-792-8163 Email: alinan@mdanderson.org), Bridget Chapital (Ph: 713-563-0064 Email: bochapital@mdanderson.org), Eliana Turk (Ph: 713-745-3467 Email: etturk@mdanderson.org), Aman Buzdar (Ph: 713-745-7139 Email: abuzdar@mdanderson.org)

1IND14767Center for Cancer ResearchDahut MD, WilliamInterleukin-15; Following Autologous Stem Cell TransplantationEGFRVIIITreatment of gliomasPeripheral Blood Lymphocytes, Autologous, Transduced with Anti-CD19 Chimeric Antigen Receptor Gene (Retroviral Vector PG13-CD19-H3)OTATACTIVE12-Dec-1411-Jul-1112-Jul-1112-Jul-11201112/5/2012-Non-secure email authorized. 5/19/16 Update Authorized Contacts: Include on all emails (nciprotocolsupportoffice@mail.nih.gov); William Dahut, MD (dahutw@mail.nih.gov); Mary Ann Toomey, RN (toomeym@mail.nih.gov; PHONE:301-435-7507); Steven A Rosenberg, MD, PhD (PHONE:301-435-7507; FAX: 301-435-7508; sar@mail.nih.gov); Nicole Grant (grantn@mail.nih.gov);

1IND14769MSKCCALLOGENEIC EPSTEIN-BARR VIRUS (EBV)-SPECIFIC CYTOTOXIC T-LYMPHOCYTES (CTL) CULTURED EX-VIVO TRANSDUCED WITH RETROVIRAL VECTOR (PG13-1928Z)CD1913-Jul-112011

1IND14802Powell Jr PhD, Daniel JKandalaft PharmD PhD, Lana EAutologous CD3+ T Cells Cultured with Interleukin-2 and Transduced with Lentiviral Vector (rELNS-Mov19-4-188-CD3zeta, City of Hope) Expressing Alpha Folate Chimeric Antigen Receptor; Following Chemotherapy; with or without Interleukin-7folateTreatment of recurrent ovarian cancerInterleukin-2, IL-2, Aldesleukin; MoAb, Murine, to CD3/CD28, Conjugated to Dynabeads; Recombinant Human Interlukin-7 (IL-7); Tcells, Autologous, Transduced with Alpha Folate Chimeric Antigen Receptor Gene (Lentiviral Vector, rELNS-Mov19-4-188-CDzeta)OTATACTIVE9-Sep-115-Aug-1112-Aug-1112-Aug-112011Sponsor authorized email communication: Dr. Lana Kandalaft (lknd@mail.med.upenn.edu)

1IND14806June MD, Carl HJune MD, Carl HAutologous T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with Lentiviral Vector (CART-19, CHOPCVC) Expressing CD19 Chimeric Antigen Receptor; with or without Autologous CD3+ T-cells Transduced with Retroviral Vector (SFG-1928z, MSKCC) Expressing CD19 Chimeric Antigen Receptor; Cultured with Interleukin-2cd19Treatment of refractory CD19+ leukemia and lymphomaAutologous CD3+ T-cells Transduced with CD19 chimeric antigen receptor gene (Retroviral Vector SFG-1928z, MSKCC); Cultured with Interleukin-2; Autologous T Cells Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen Receptor; Interleukin-2, IL-2, AldesleukinOTATACTIVE21-Sep-1110-Aug-1122-Aug-1122-Aug-112011Sponsor authorize communication via unsecure email in original submission. Alt contacs Anne Chew (achew@mail.med.upenn.edu) and Elizabeth Veloso (eveloso@mail.med.upenn.edu)

withdrawnIND14864BEATTY MD PHD, GREGORY LAUTOLOGOUS T CELLS TRANSFECTED WITH MESSENGER RNA EXPRESSING CHIMERIC ANTI-MESOTHELIN IMMUNORECEPTOR; ADMINISTERED INTRAVENOUSLYmesopancreatic cancer

single patientIND14868June MD, Carl HVeloso JD BSN, Elizabeth AAllogeneic T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen Receptorcd19Treatment of a single patient with relapsed acute lymphocytic leukemiaAllogeneic T Cells Transduced with CD19 Chimeric Antigen Receptor Lentiviral Vector (CART-19, Lentigen); Anti CD3, Anti CD28 Coated Magnetic Beads; aNTI-cd28 magnetic beadsOTATACTIVE4-Nov-1127-Sep-115-Oct-115-Oct-11

withdrawnIND14941June MD, Carl HVeloso JD BSN, Elizabeth AAllogeneic-unrelated T cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads, Transduced with Lentiviral Vector (pLTG119, Lentigen)) Expressing anti-CD19-zeta-4-1BB Chimeric Antigen Receptor (CART-19)cd19Treatment of relapsed CD19+ acute lymphocytic leukemia.Allogeneic T cells Transduced with Lentiviral Vector (pLTG119, Lentigen) Expressing anti-CD19-zeta-4-1BB Chimeric Antigen Receptor (CART-19); Lentiviral Vector (pLTG119, Lentigen) Expressing anti-CD19-zeta-4-1BB Chimeric Antigen Receptor (CART-19)OTATWITHDRAWN5-Jan-172-Dec-1114-Dec-1114-Dec-111/6/2012 - Non-secure email authorization for Carl H. June, M.D., at cjune@exchange.upenn.edu;Authorized Contacts: Elizabeth Veloso (PHONE: 215-746-5538; FAX: 215746-8907; EMAIL: eveloso@mail.upenn.edu)

1IND14985National Cancer InstituteDahut MD, WilliamAutologous Peripheral Blood Lymphocytes; Cultured with OKT3 and Interleukin-2; Transduced with Retroviral Vector (PG13-CD19-H3) Expressing Anti CD19 Chimeric Antigen Receptor Genecd19Treatment of advanced B-cell malignanciesAldesleukin [Proleukin]; Dynabeads coated with Murine Monoclonal anti-CD3/CD28; MoAb, OKT3, Murine, to CD3+ [Orthoclone OKT3]; Peripheral Blood Lymphocytes, Autologous, Transduced with Anti-CD19 Chimeric Antigen Receptor Gene (Retroviral Vector PG13-CD19-H3)OTATACTIVE17-Aug-1524-Jan-1226-Jan-1226-Jan-122012Permission to communicate via non-secure email is given in original submission. 7/16/2015 Authorized Contacts - Dr. Terry Fry (PHONE: 301-402-0215; F: 301-451-7010; terry.fry@nih.gov); Dr. Daniel Lee (PHONE: 301-435-6236; Email: leed3@mail.nih.gov)

1IND14989Center for Cancer ResearchDahut MD, WilliamAutologous Peripheral Blood Lymphocytes Transduced with Retroviral Vector (Pg13-coSS1scFv-28Z) Expressing Anti-mesothelin Chimeric Antigen Receptor Gene; and Interleukin-2mesoTreatment of metastatic cancersPeripheral Blood Lymphocytes, Autologous, Transduced with Anti-mesothelin chimeric antigen receptor gene (retroviral vector, Pg13-coSS1scFv-28z)OTATACTIVE26-Feb-1217-Jan-1227-Jan-1227-Jan-12201212/5/2012-Non-secure email authorized. Authorized Contacts: Mary Ann Toomey, RN, Surgery Branch Protocol Support Office (EMAIL: toomeym@mail.nih.gov;PHONE:301-435-7507); Steven A Rosenberg, MD, PhD (PHONE:301-435-7507; FAX: 301-435-7208; EMAIL:sar@mail.nih.gov)

1IND15014UpennAUTOLOGOUS T CELLS TRANSFECTED WITH MESSENGER RNA EXPRESSING ANTI-CMET CHIMERIC ANTIIGEN RECEPTOR GENEcmetbreast cancer24-Feb-122012

1IND15017Turtle MBBS PhD, CameronTurtle MBBS PhD, CameronAllogeneic CD8+, EBV or CMV Specific T cells, CD62 Enriched (Anti-CD62L-Biotin, City of Hope),Transduced with Lentiviral Vector (CD19R-CD28gg-z-T2A-EGFRt_epHIV7, City of Hope) Expressing CD19-specific Chimeric Antigen Receptorcd19Treatment of CD19+ B cell malignanciesCliniMACS CD 14+ Reagent System; CliniMACS CD4 Reagent System; CliniMACS CD45RA Reagent Systems; T Cells, Allogeneic, Transduced withCD-19 specific CAR (Lentiviral vector, CD19R-CD28gg-¿-T2A-EGFRt_epHIV7)OTATACTIVE28-Mar-1222-Feb-1224-Feb-1227-Feb-1220123/2/12 - Sponsor authorized nonsecure email with Cameron Turtle (PHONE: 206-667-7073; FAX: 206-667-7983; EMAIL: cturtle@fhcrc.org), Susan Lemmon (slemmon@fhcrc.ort), Colette Chaney (cchaney@fhcrc.org), and Stanley Riddell (sriddell@fhcrc.org)

1IND15180Univ of TexasBuzdar MD, AmanAutologous CD19 Specific T cells Transduced with DNA Plasmid Vectors (Sleeping Beauty System) Expressing Chimeric Antigen Receptor; Co-cultured with Gamma-irradiated K562 Tumor Cell Line Transduced with Lentiviral Vectors; with or without Interleukin-2cd19Treatment of chronic lymphocytic leukemia.Interleukin-2, IL-2, Aldesleukin; Interleukin-21; K-562 Cell Line Transduced with CD19 gene (Lentiviral Vector); T Cells, Allogeneic, Transfected with CD19 Specific Chimeric Antigen Receptor (Sleeping Beauty Plasmid DNA)OTATACTIVE7-Aug-1210-Jul-1211-Jul-1211-Jul-122012Protocol # 2011-1169, Version 03, 6/12/12, title: "Autologous CD19-Specific T-cell Infusion in Patients with B-cell Chronic Lymphocytic Leukemia (B-CLL)"

1IND15229SCRI Program in Cell & Gene TherapyJensen MD, Michael CAutologous T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads and Transduced with Lentiviral Vector ( CD19R-CD28gg-zeta-T2A-EGFRt_epHIV7) Expressing CD19 Chimeric Antigen Receptor (CAR); Expanded with Interleukin-2 and Interleukin-15; Infused Following Cyclophosphamide.cd19Treatment of acute lymphoblastic leukemia.Autologous T Cells Transduced with Lentiviral Vector ( CD19R-CD28gg-zeta-T2A-EGFRt_epHIV7) Expressing CD19 Chimeric Antigen Receptor (CAR); Dynal CD28 CTS beads; Dynal CD3 CTS beads; Lentiviral Vector ( CD19R-CD28gg-zeta-T2A-EGFRt_epHIV7) Expressing CD19 Chimeric Antigen Receptor (CAR); rhuIL-15; rhuIL-2 (Proleukin)OTATACTIVE28-Sep-1230-Aug-1231-Aug-1231-Aug-122012Secure email authorized. Authorized Contacts: Dr. Michael Jensen (PHONE:(206) 987-1241;FAX:206-884-4100; EMAIL: michael.jensen@seattlechildrens.org); Catherine Lindgren (EMAIL: catherine.lindgren@seattlechildrens.org; Phone: 206-884-4366)

1IND15445Doolittle MD, GaryDoolittle MD, GaryAutologous T Cells Transduced with Retroviral Vector, SFG.14G2A.Zeta.5, Encoding a Chimeric Antigen Receptor to disialoganglioside-GD2 (GD2 CAR); Cultured with CD28, CD3, and IL-2; Following Cyclophosphamide and Tdap, HepB, and IPV Vaccines; Administered Intravenously.gd2Treatment of relapsed/refractory melanoma.Peripheral blood T cells, Autologous, Transduced with GD2CAR Gene (Retroviral Vector SFG14aZeta5)OTATACTIVE12-Jul-1322-Mar-1325-Mar-1327-Mar-1320134/22/2013 - Non-secure email authorized. Authorized Contacts: Gary Doolittle, MD (PHONE: 913-588-6029; FAX: 913-588-4085; EMAIL:GDOOLITT@kumc.edu); Kelly Scott (PHONE: 913-588-4761; FAX: 913-588-4085; EMAIL:kscott5@kumc.edu). 8/1/2013 - Additional Contacts: Dr. Joy Fulbright (EMAIL: jmfulbright@cmh.edu); Dr. Douglas Myers (EMAIL: gdmyers@cmh.edu)

1IND15453Riddell MD, Stanley RRiddell MD, Stanley RAutologous CD8+, CD4+ T Cells (Miltenyi CliniMACS) Transduced with Self-Inactivating Lentiviral Vector (ZRX-014-LV) Encoding a CD19-specific Chimeric Antigen Receptor (CD19 CAR) and Truncated Epidermal Growth Factor Receptor (EGFRt); Cultured with CD28, CD3, and IL-2; Following Chemotherapy; Administered Intravenously.cd19Treatment of CD19+ B cell malignancies.Autologous CD8+, CD4+ T Cells (Miltenyi CliniMACS) Transduced with Self-Inactivating Lentiviral Vector (ZRX-014-LV) Encoding a CD19-specific Chimeric Antigen Receptor (CD19 CAR) and Truncated Epidermal Growth Factor Receptor (EGFRt); Biotinylated anti-CD62L mAb; CiiniMACS-CD14 Reagent; CiiniMACS-CD4 Reagent; CiiniMACS-CD45RA Reagent; Dynabeads CD28 CTS; Dynabeads CD3 CTS; Lentiviral Vector Encoding a CD19-specific Chimeric Antigen Receptor (CD19 CAR) and Truncated Epidermal Growth Factor Receptor (ZRX-014-LV); TM-LCLOTATACTIVE24-Feb-1428-Mar-1329-Mar-1329-Mar-1320134/15/2013 - Non-secure email authorized. Authorized Contacts: Dr. Stanley Riddell (Phone: 206-667-5249; E-mail: sriddell@fhcrc.org); Dr. Cameron Turtle (Phone: 206-667-7073; E-mail: cturtle@fhcrc.org); Susan Lemmon (Phone: 206-667-1184; E-mail: slemmon@fhcrc.org) and David Maloney - dmaloney@fredhutch.org

1IND15490City of HopeMatsumoto, CatherineAutologous CD62L+ Central Memory T cells; Transduced with Lentiviral Vector rJ02104-4 (CD19R:CD28:zeta(CO)-T2A-EGFRt_epHIV7) Expressing CD19-Specific, CD28-Costimulatory Chimeric Antigen Receptor and Truncated EGFR (EGFRt); CD3/CD28 Activated; Cultured with Cytokines.cd19Treatment of high risk intermediate Grade B-Lineage non-Hodgkin Lymphoma.Autologous Peripherial Blood Mononuclear CellsOTATACTIVE31-May-1329-Apr-133-May-133-May-132013Secure email established. 5/31/2016 Updated Contacts: Catherine Matsumoto (P:626-471-7202, F:626-301-8117;cmatsumoto@coh.org); Larry Kwak, MD, PhD (P: 626-256-4673 x80025; lkwak@coh.org)

1IND15609CAGTAUTOLOGOUS ACTIVATED T LYMPHOCYTES TRANSDUCED WITH RETROVIRAL VECTOR (SFG.ICASP9.2A.CAR-GD2.CD28.OX40ZETA) EXPRESSING GD2 SPECIFIC CAR AND INDUCIBLE CASPASE 9 SUICIDE GENE (IC9-GD2 T CELLS); CULTURED WITH CYTOKINES; AND AP 1903.gd25-Jun-132013

single patientIND15717Mackall MD, Crystal LMackall MD, Crystal LSyngeneicT Cells Cultured with OKT3 and Interleukin-2; Transduced with Retroviral Vector (PG13-CD19-H3) Expressing Anti CD19 Chimeric Antigen Receptor Gene (CAR19).cd19Emergency - Single patient with refractory ALLSyngeneicT Cells Cultured with OKT3 and Interleukin-2; Transduced with Retroviral Vector (PG13-CD19-H3) Expressing Anti CD19OTATACTIVE20-Aug-1320-Aug-1320-Aug-1320-Aug-138/21/2013 - Non-secure email authorized. Authorized Contacts: Sponsor: Crystal L Mackall, MD (ph: 301-402-5940; fax: 301-451-7010; email: cm35c@nih.gov); Daniel Trey Lee (EMAIL: leed3@mail.nih.gov; PHONE: 301-957-1933); Sharon Mavroukakis (EMAIL: mavrouks@mail.nih.gov; PHONE: 301-231-4876) Crystal L. Mackall, MD Address:Building 10, Room 1-5809 10 Center Drive City: Bethesda State: MD ZIP: 20892 Contact: CANDACE MENKE Contact Phone: 3014515007 Ext:

1IND15754Center for Cell and Gene TherapyBrenner MD PhD, Malcolm KAutologous or Syngeneic CD3/CD28 Activated T cells Transduced with Retroviral Vectors Expressing CD19 Chimeric Antigen Receptor with CD28 (SFG.CD19.CAR-CD28zeta) or CD19 Chimeric Antigen Receptor with CD28 and CD137 (SFG.CD19.CAR-CD28/CD137zeta) Cultured with Cytokines.cd19Treatment of patients with refractory/relapsed indolent and aggressive B-cell Non-Hodgkin Lymphomas (NHL), including chronic lymphocytic leukemia (CLL).Autologous activated peripheral blood T lymphocytes modified to express artificial T-cell receptors targeting CD19; Retroviral vectors: replication incompetent Moloney murine leukemia virus-based vectors encoding the CARSOTATACTIVE18-Oct-1312-Sep-1318-Sep-1318-Sep-1320139/20/2013 - Non-secure email authorized. Authorized Contacts: Helen Heslop (PHONE: 832-824-4671; EMAIL: hheslop@bcm.edu); Malcolm Brenner ((PHONE: 832-824-4671; EMAIL: mbrenner@bcm.edu); Bambi Grilley ((PHONE: 832-824-3893; EMAIL: grilley@bcm.edu).

1IND15801Univ of Pennsylvania Medical CenterMeagher MD, Emma AAutologous CD3+ T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with self-inactivating (SIN) Lentiviral Vector (CD19bbz-human Lot# 060713S12) Expressing Humanized CD19 Chimeric Antigen Receptor (huCART19)cd19Treatment of CD19+ hematologic malignanciesAutologous CD3+ T-cells Transduced with CD19 chimeric antigen receptor gene (Retroviral Vector SFG-1928z, MSKCC); Cultured with Interleukin-2; Autologous T Cells Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen Receptor; Interleukin-2, IL-2, AldesleukinOTATACTIVE27-Nov-1317-Oct-1330-Oct-1330-Oct-132013Authorized to communicate with (amendment 53): Emma Meagher - emma@exchange.upenn.edu, Carl June - cjune@exchange.upenn.edu, Elizabeth Hexner - Elizabeth.Hexner@uphs.upenn.edu, Katherine Marcucci - kmarcu@exchange.upenn.edu, Laura Mullens - lmullens@upenn.edu, Deanna DiDonato - deannad@upenn.edu, Shelly Fehr - sfehr@upenn.edu)

1IND15828Center for Cell and Gene TherapyBrenner MD PhD, Malcolm KAutologous Varicella Zoster Virus(VZV)-Specific T Cells Co-cultured with Autologous Dendritic Cells Pulsed with Peptides, and Autologous PBMC Pulsed with VZV Peptides; Transduced with Retroviral Vector Expressing GD2 Chimeric Antigen Receptor; Expanded with K562 Erythroid Leukemia Cell Line and Autologous T Cells Pulsed with Peptides.gd2Treatment of refractory or metastatic sarcomaAutologous T lymphocytesOTATACTIVE28-Feb-1413-Nov-1319-Nov-1319-Nov-13201311/13/2013-Cover letter authorized non-secure email. Authorized Contacts: Helen Heslop, MD (832-824-4671; EMAIL: hheslop@bcm.edu); Malcolm Brenner, MD (PHONE: 832-824-4671; FAX: 832-825-4203; EMAIL: mbrenner@bcm.edu); Bambi Grilley, RPh (PHONE: 832-824-3893; EMAIL: grilley@bcm.edu).

1IND15829SCRI Program in Cell & Gene TherapyJensen MD, Michael CAutologous CD4+/CD8+T Cells Activated with CD3/CD28 Microbeads; Transduced with Lentiviral Vector (ZRX-014-LV, City of Hope) Expressing CD19-Specific Chimeric Antigen Receptor and EGFRt; Cultured with Interleukin-2, Interleukin-7, and Interleukin-15cd19Treatment of CD19+ Malignancies in Pediatric PatientsAutologous Peripheral Blood T Cells Transduced with Lentiviral Vector (ZRX-014-LV) Encoding a CD19-specific Chimeric Antigen Receptor (CD19 CAR); CD3/CD28 CTS Dynabeads; Lentiviral Vector Encoding a CD19-specific Chimeric Antigen Receptor (ZRX-014-LV)OTATACTIVE31-Mar-1718-Nov-1319-Nov-1319-Nov-132013Secure email established; email authorized. Authorized Contacts: Michael Jensen, MD (EMAIL: Michael.Jensen@seattlechildrens.org; Phone: 206-987-1241); Catherine Lindgren (EMAIL: catherine.lindgren@seattlechildrens.org; Phone: 206-884-4366)

1IND15845Center for Cancer ResearchDahut MD, WilliamAutologous CD3+ Peripheral T Lymphocytes Transduced with Retroviral Vector (anti-GD2.28.z.OX40.ICD9) Expressing anti-GD2 Chimeric Antigen Receptor; Cultured with Cytokines; Following Cyclophosphamide; Tocilizumab and AP-1903 Administered as Needed.gd2Treatment of osteosarcoma or non-neuroblastoma, GD2+ solid tumors in children and young adults.Autologous CD3+ Peripheral T Lymphocytes Transduced with Retroviral Vector (anti-GD2.28.z.OX40.ICD9) Expressing anti-GD2OTATACTIVE26-Aug-1525-Nov-1327-Nov-1327-Nov-13201312/2/2013 - Non-secure email authorized. Authorized Contacts: Crystal L Mackall, MD (PHONE: 301-402-5940; fax: 301-451-7010; email: cm35c@nih.gov); Melinda Merchant MD, PhD (PHONE: 301-443-7955; EMAIL: merchanm@mail.nih.gov); Sharon Mavroukakis (PHONE: 301-231-4876; EMAIL: mavrouks@mail.nih.gov)

1IND15882Univ of PennsylvaniaMeagher MD, Emma AAutologous CD3+ T Cells cultured with Anti-CD3 & Anti-CD28 Coated Magnetic Beads, Transduced with Self-Inactivating (SIN) Lentiviral Vector (SS1.BBz CAR) Expressing Anti-Mesothelin Chimeric Antigen Receptor (CART-meso cells); With or Without Cyclophosphamide Pre-Conditioning Chemotherapy.mesoTreatment of Patients with Mesothelin Expressing CancersAutologous CD3+ T-cells Transduced with CD19 chimeric antigen receptor gene (Retroviral Vector SFG-1928z, MSKCC); Cultured with Interleukin-2; Autologous T Cells Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen Receptor; Interleukin-2, IL-2, AldesleukinOTATACTIVE23-Jan-1423-Dec-1324-Dec-1324-Dec-132013Permission to communicate via e-mail with: Emma Meagher - emma@exchange.upenn.edu, Gabriela Plesa - gplesa@exchange.upenn.edu), Deanna DiDonato - deannad@exchange.upenn.edu and Shelly Fehr - sfehr@exchange.upenn.edu

single patientIND15951Gardner MD, RebeccaGardner MD, RebeccaAutologous T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads and Transduced with Lentiviral Vector ( CD19R-CD28gg-zeta-T2A-EGFRt_epHIV7) Expressing CD19 Chimeric Antigen Receptor (CAR); Expanded with Interleukin-2 and Interleukin-15.cd19Treatment of acute Lymphoblastic Leukemia in a single patient.Autologous T Cells Transduced with Lentiviral Vector ( CD19R-CD28gg-zeta-T2A-EGFRt_epHIV7) Expressing CD19 Chimeric Antigen Receptor (CAR); Lentiviral Vector ( CD19R-CD28gg-zeta-T2A-EGFRt_epHIV7) Expressing CD19 Chimeric Antigen Receptor (CAR); rhuIL-2/IL-15OTATACTIVE11-Mar-1428-Feb-146-Mar-146-Mar-143/7/2014 - Non-secure email authorized. Authorized contact:Rebecca Gardner, MD (Phone: (206) 884-1087; Fax: (206) 884-4100; Email:Rebecca.Gardner@seattlechildrens.org)

1IND15968Univ of PennsylvaniaMeagher MD, Emma AAutologous CD4+ and CD8+ T cells (CART-EGFRvIII) Cultured with Dynabeads CD3/CD28 CTS; Transduced with Lentiviral Vector Expressing EGFRvIII-specific chimeric antigen receptor (huEGFRvIII.BBz); Following Chemoradiation; Before Temozolomide; Administered Intraveneously.egfrviiiTreatment of EGFRvIII+ Glioblastoma.Autologous T Cells Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen ReceptorOTATACTIVE10-Apr-147-Mar-1414-Mar-1414-Mar-142014Amendment 25 - Non-secure email authorized.Authorized Contacts: Emma Meagher - emma@exchange.upenn.edu, Gabriela Plesa - gplesa@exchange.upenn.edu, Elizabeth Hexner - Elizabeth.Hexner@uphs.upenn.edu, Carl June - cjune@exchange.upenn.edu, Judith LaLonde - judithla@exchange.upenn.edu, Deanna Didonato - deannad@exchange.upenn.edu, Shelly Fehr - sfehr@exchange.upenn.edu

single patientIND16027Mackall MD, Crystal LMackall MD, Crystal LAutologous Peripheral Blood Lymphocytes; cultured with OKT3 and Interleukin-2; Transduced with Retroviral Vector (PG13-CD19-H3) Expressing Anti CD19 Chimeric Antigen Receptor Gene.cd19For the emergency treatment of a single patient (AI) with relapsed, refractory pre-B acute lymphoblastic leukemia (ALL).Autologous Peripheral Blood Lymphocytes; Transduced with Retroviral Vector (PG13-CD19-H3) Expressing Anti CD19 Chimeric Antigen Receptor GeneOTATACTIVE23-May-1423-May-1423-May-1423-May-14Sponsor: CRYSTAL MACKALL Address:NCI, 10-CRC, !W-3750, 10 Center Drive MSC 1104 City: Bethesda State: MD ZIP: 20892 Contact: SHARON MAVROUKAKIS Contact Phone: 3012314876 Ext:

1IND16041Center for Cancer ResearchDahut MD, WilliamAutologous Peripheral Blood Lymphocytes (PBLs) Transduced with Retroviral Vector (PG13-MSGV-11D5-3CD82Z B1, NCI) Expressing Anti-B-cell maturation antigen (BCMA) Chimeric Antigen Receptor (CAR); Cultured with Cytokines; Following Chemotherapy.bcmaTreatment of Multiple Myeloma.Autologous T Cells Transduced with Retroviral Vector (PG13-MSGV-11D5-3CD82Z B1, NCI) Expressing Anti-B-cell maturation antigen (BCMA) Chimeric Antigen ReceptorOTATACTIVE10-Jul-145-Jun-149-Jun-149-Jun-1420146/5/2014-Non-secure email authorized in submission. Authorized Contacts: Dr. James Kochenderfer (PHONE: 301-496-4251; FAX: 301-480-4354; EMAIL: kochendj@mail.nih.gov); Nicole Grant (EMAIL: grantn@mail.nih.gov); include NCI Protocol Support office in all emails (EMAIL: nciprotocolsupportoffice@mail.nih.gov)

1IND16067Univ of TexasBuzdar MD, AmanAutologous Peripheral Blood Mononuclear Cells Transduced with Sleeping Beauty Plasmid DNA System Expressing ROR1 Chimeric Antigen Receptor (ROR1R-CAR); Co-cultured with Gamma-irradiated K562 aAPC Tumor Cell Line Transduced with Lentiviral Vectors Expressing CD19, CD64, CD86, CD137L, IL-15/IL-15Ralpha, and ROR1; Following Chemotherapy.ror1Treatment of Patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Leukemia (SLL).Autologous Peripheral Blood Mononuclear Cells Transduced with Sleeping Beauty Plasmid DNA System; Gamma-irradiated K562 aAPC Tumor Cell Line Transduced with Lentiviral VectorsOTATACTIVE29-Jul-1427-Jun-1430-Jun-1430-Jun-1420147/7/2014 Non-secure email authorized. Authorized Contacts: Aman Buzdar, MD (PHONE: 713-563-1863;FAX: 713-792-8987; Email: abuzdar@mdanderson.org); Eliana Turk, MD, MPH (713-745-3467, etturk@mdanderson.org); Sean O'Connor, PhD (EMAIL: soconnor@mdanderson.org); Stella Tsai (PHONE: 713/563-5464; EMAIL: swtsai@mdanderson.org); Felicia Nica, MD (PHONE: 713/792-8163; EMAIL: alinan@mdanderson.org); Bridget Chapital, MEd, CCRP (PHONE: 713/563-0064; EMAIL: bochapital@mdanderson.org)

1IND16130Novartis Pharmaceuticals CorpPatel PharmD, ManishaAutologous T Cells Elutriated or Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with Lentiviral Vector Expressing CD19 Chimeric Antigen Receptorcd19Treatment of Acute Lymphoblastic Leukemia (ALL)Autologous T Cells Transduced with Lentiviral Vector Expressing CD19 Chimeric Antigen Receptor (CTL019); Dynabeads CD28; Dynabeads CD3; Human AB serum; Lentiviral Vector Expressing CD19 Chimeric Antigen Receptor; Recombinant Human Proleukin (Aldesleukin)OTATACTIVE13-Feb-1523-Sep-1423-Sep-1423-Sep-142014Authorized to communciate: Narin Hussain - narin.ahmed@novartis.com, Jonelle Chapman - jonelle.chapman@novartis.com, Manisha Patel - manisha.patel@novartis.com. CMC specificLisa Kahn - lisa.kahn@novartis.com and Cindy Riggins - cindy.riggins@novartis.com Authorized to make submissions and authorized to sign 1571 see 1Nov16 t-con.

1IND16139Seattle Children's Research InstituteJensen MD, Michael CAutologous CD4+ and CD8+T Cells Transduced with SIN Lentiviral Vector Expressing 4-1BB:zeta (CE7CAR(2G)-T2A-EGFRt) or CD28:4-1BB:zeta (CE7CAR(3G)-T2A-EGFRt) CD171-Specific Chimeric Antigen Receptor and a truncated EGFR; Cultured with Cytokines; Following Cyclophosphamide.ce7Treatment of recurrent/refractory neurblastoma.OTATACTIVE26-Sep-1426-Aug-1427-Aug-1427-Aug-142014Secure email established. Authorized Contacts: Michael Jensen (EMAIL: michael.jensen@seattlechildrens.org)

1IND16180Center for Cancer ResearchDahut MD, WilliamAutologous T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads and Cytokines; Transduced with Lentiviral Vector (Ef1a-BBZ-CD22-CAR) Expressing CD22 Chimeric Antigen Receptor (anti-CD22 CAR); Following fludarabine and cyclophosphamide.cd22Treatment of CD22-expressing B-cell malignancies including acute lymphoblastic leukemia (ALL) or lymphoma.Autologous T Cells Transduced with Lentiviral Vector (Ef1a-BBZ-CD22-CAR) Expressing CD22 Chimeric Antigen Receptor (anti-CD22 CAR); Lentiviral Vector (Ef1a-BBZ-CD22-CAR) Expressing CD22 Chimeric Antigen Receptor (anti-CD22 CAR)OTATACTIVE13-Apr-1618-Sep-1423-Sep-1423-Sep-1420149/30/2014 - Non-secure email authorized. 1.13.17 Update Authorized Contacts: INCLUDE ON ALL EMAILS (nciprotocolsupportoffice@mail.nih.gov); William Dahut MD (dahutw@mail.nih.gov); Nicole Grant (PHONE: 301-272-0476;grantn@mail.nih.gov). R.Rita Mistra P; 240-276-6123 F: 240-276-7885 E: misrar@ctep.nci.nih.gov

1IND16182UPennAUTOLOGOUS T CELLS CULTURED WITH ANTI-CD3 AND ANTI-CD28 BEADS TRANSFECTED WITH ANTI-CD19 MESSENGER RNA EXPRESSING CHIMERIC RECEPTORS; ADMINISTERED INTRAVENOUSLYcd1928-Oct-142014

1IND16226City of Hope National Medical CenterMatsumoto, CatherineAutologous CD62 Enriched (Anti-CD62L-Biotin, City of Hope) CD3/CD28 Activated T cells Transduced with Self-Inactivating (SIN) Lentiviral Vector (IL13(EQ)BBZ-T2A-CD19t_epHIV7) Expressing IL-13 Receptor alph-2 (IL13R-alpha-2) and Truncated Human CD19 Specific Chimeric Antigen Receptor (CAR) Cultured with Cytokines; Following Tumor Biopsy/Resection; Intracavitary/Intratumoral Administration.cd19For the treatment of recurrent/refractory malignant glioma.Autologous ex vivo expanded central memory-enriched T cellOTATACTIVE12-Mar-1527-Oct-1428-Oct-1428-Oct-14201410/29/2014 - Non-secure email authorized until secure email is established. 5/31/16 Authorized Contacts: Catherine Mastumoto (PHONE: 626-471-7202; Fax: 626-256-8730; EMAIL: cmatsumoto@coh.org); Larry Kwak, MD, PhD (PHONE: 626-256-4673 x80025; lkwak@coh.org);

1IND16271Univ of PennsylvaniaMeagher MD, Emma AAutologous CD4+/CD8+ T cells Transduced with Self-Inactivating (SIN) Lentiviral Vectors (SS1.BBz or CD19.BBz) Expressing Mesothelin-Specific Chimeric Antigen Receptor (CART-meso) or CD19-Specific Chimeric Antigen Receptor (CART19) Combined (CART-meso-19); Cultured with Cytokines; Following Cyclophosphamide.cd19For the treatment of pancreatic cancer. Additional Contact: ;Shelly Fehr (P: 215-662-4639; sfehr@exchange.upenn.edu)Autologous CD3+ T-cells Transduced with CD19 chimeric antigen receptor gene (Retroviral Vector SFG-1928z, MSKCC); Cultured with Interleukin-2; Autologous T Cells Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen Receptor; Interleukin-2, IL-2, AldesleukinOTATACTIVE19-Dec-1417-Nov-1421-Nov-1421-Nov-142014Non-secure email authorized. Amendment 17: Emma Meagher - emma@exchange.upenn.edu, Gabriela Plesa - gplesa@exchange.upenn.edu, Bruce Giantonio - Bruce.Giantonio@uphs.upenn.edu, Xuan-Duyen Huynh - xhuynh@exchange.upenn.edu, Deanna DiDonato - deannad@exchange.upenn.edu, Shelly Fehr - sfehr@exchange.upenn.edu

1IND16278Kite Pharma IncSproule PhD, Rizwana FAutologous Peripheral Blood T Cells Transduced with Retroviral Vector (PG13-CD19-H3) Expressing anti-CD19 CD28/CD3-zeta chimeric antigen receptor (CAR); and Cultured with Cytokines; Following Fludarabine and Cyclophosphamide, [Product: KTE-C19]cd19For the treatment of adult subjects with refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B cell lymphoma (PMBCL) and transformed follicular lymphoma (TFL).Autologous Peripheral Blood T Cells Transduced with Retroviral Vector (PG13-CD19-H3) Expressing anti-CD19 CD28/CD3-zeta chimeric antigen receptor (KTE-C19 CAR); Cryostor CS10; MACS GMP CD3 pure; Recombinant IL-2; Retroviral Vector (PG13-CD19-H3) Expressing anti-CD19 CD28/CD3-zeta chimeric antigen receptor (KTE-C19 CAR)OTATACTIVE29-Oct-1519-Dec-1423-Dec-1423-Dec-14201412/29/2014-Non-secure email authorized. Authorized Contacts: Rizwana F Sproule, PhD (Office: (424) 209-1332; Mobile: (805) 276-8586; EMAIL: rsproule@kitepharma.com); Alex Babayan, PhD (Office: (484) 322-1938; Mobile: (818) 448-1288; EMAIL:ababayan@kitepharma.com)

1IND16354Memorial Sloan-Kettering Cancer CenterHo MD PhD, AlanAutologous T Cells Transduced with Gammaretroviral Vector (SFG-iCASP9-2A-M28z) Encoding Mesothelin-specific Chimeric Antigen Receptor and iCaspase9 (iCasM28z CAR T cells); With and Without Cyclophosphamide; Administered Intrapleurally.mesoTreatment of patients with a histologically or cytologically diagnosed mesothelin-positive malignant pleural disease (MPD).Autologous T Cells Transduced with Gammaretroviral Vector (SFG-iCASP9-2A-M28z) Encoding Mesothelin-specific Chimeric AntigenOTATACTIVE11-Mar-155-Feb-156-Feb-159-Feb-1520152/17/2015-Non-secure email authorized. Authorized Contacts: Dr. Alan Ho; Richard Ellis (Phone: (646) 888-0927; Fax: (646) 888-0940; EMAIL: ellisr@MSKCC.ORG).

1IND16457City of Hope National Medical CenterMatsumoto, CatherineAutologous CD3/CD28 Activated T cells Transduced with Lentiviral Vector Expressing CD123-specific, Hinge-Optimized, CD28-Costimulatory Chimeric Antigen Receptor (CAR) and Truncated Human Epidermal Growth Factor Receptor (CD123R(EQ)28Z-EGFRt_epHIV7); Cultured with Cytokines; Following Cyclophosphamide.cd123For the treatment of relapsed or refractory CD123+ acute myeloid leukemia (AML).T Cells, Autologous, Transduced with Lentiviral Vector (CD123R(EQ)28Z-EGFRt_epHIV7, City of Hope)OTATACTIVE21-May-1520-Apr-1521-Apr-1521-Apr-152015Secure email established. 5/31/2016 Updated Contacts: Catherine Matsumoto (P:626-471-7202, F:626-301-8117;cmatsumoto@coh.org); Larry Kwak, MD, PhD (P: 626-256-4673 x80025; lkwak@coh.org)

1IND16463Univ of PennsylvaniaMeagher MD, Emma AAutologous T Cells Transfected with Messenger RNA Expressing Chimeric Antigen Receptor (Anti?GD2); Administered Intravenouslygd2Recurrent or Refractory NeuroblastomaAutologous T Cells Transfected with Messenger RNA Expressing Chimeric Antigen Receptor (Anti¿GD2)OTATACTIVE27-May-1524-Apr-1527-Apr-1527-Apr-152015Permission to communicate via non-secure e-mail with: Emma Meagher , Katherine Marcucci, PhD , Praharsh Shah - prahp@upenn.edu, Judith LaLonde - judithla@upenn.edu, Shelly Fehr - sfehr@upenn.edu

1IND16474Univ of TexasBuzdar MD, AmanAutologous or Allogeneic T Cells Derived from Peripheral Blood Mononuclear Cells Transduced with DNA Plasmid Vectors (Sleeping Beauty System) Expressing CD19 Chimeric Antigen Receptor with a CD8alpha Stalk Region; by Electroporationcd19Advanced Lymphoid MalignanciesAutologous or Allogeneic T Cells Derived from Peripheral Blood Mononuclear Cells Transduced with DNA Plasmid Vectors (Sleeping Beauty System) Expressing CD19 Chimeric Antigen Receptor with a CD8alpha Stalk Region; by ElectroporationOTATACTIVE28-May-1530-Apr-151-May-151-May-152015Permission to communicate via non-secure e-mail with: Jose Arriaga , Stella Tsai , Sean O'Connor , Felicia Nica - alinan@mdanderson.org, Bridget Chapital - bochapital@mdanderson.org,

1IND16506Juno Therapeutics IncKim, HelenAutologous CD4+ and CD8+ T cells (JCAR017) Transduced with Self-Inactivating (SIN) Lentiviral Vector (ZRX-014-LV) Encoding CD19-specific Chimeric Antigen Receptor (CAR) and Truncated Epidermal Growth Factor Receptor (EGFRt); Following Fludarabine and Cyclophosphamidecd19Treatment for patients with relapsed or refractory (R/R) aggressive large B-cell non-Hodgkin lymphoma (NHL), including diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS; de novo or transformed from indolent lymphoma), primary mediastinal B-cell lymphoma (PMBCL), or Grade 3B follicular lymphoma (FL).Autologous CD4+ and CD8+ T cells Transduced with Self-Inactivating (SIN) Lentiviral Vector (ZRX-014-LV) Expressing CD19-specific Chimeric Antigen Receptor (CAR) and Truncated Epidermal Growth Factor Receptor (JCAR017); CD28 CTS Dynabeads; CD3 CTS Dynabeads; Self-Inactivating (SIN) Lentiviral Vector Expressing CD19-specific Chimeric Antigen Receptor (CAR) and Truncated Epidermal Growth Factor Receptor (ZRX-014-LV); recombinant human IL-15; recombinant human IL-2 (Proleukin); recombinant human IL-7OTATACTIVE26-Jun-1529-May-1529-May-1529-May-1520156/18/2015 - Secure email established. Authorized Contact: Helen Kim (helen.kim@junotherapeutics.com); Bentley Moyer (Phone: 206-582-1646; Email: bentley.moyer@junotherapeutics.com); Elizabeth C. Smith (Office: 206-582-1610; Mobile: 206-719-4366; elizabeth.smith@junotherapeutics.com) 4/17/2016 Orphan Designation for Diffuse Large B-cell Lymphoma (DLBCL).

single patientIND16522Levine MD, John ELevine MD MS, John EAutologous T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen Receptor; Following Fludarabine and Cyclophosphamide.cd19To treat chemotherapy resistant/ refractory CD19+ accute lymphblastic leukemia (ALL) in a Single Patient.OTATWITHDRAWN10-Feb-172-Jun-154-Jun-154-Jun-156/8/2015 - Non-secure email authorized. Authorized Contacts: John E. Levine, MD, MS (OFFICE: 734-936-8456; CLINIC:734-936-9814; FAX: 734-936-8788; EMAIL: jelevine@med.umich.edu); Kevin Weatherwax (OFFICE: 734-998-6275; CELL:734-646-0455; EMAIL: kweath@med.umich.edu)

1IND16539Univ of PennsylvaniaMeagher MD, Emma AAutologous T cells Transduced with Lentiviral Vector (AntiBCMAbbz human) Expressing B-cell Maturation Antigen (BCMA)-specific Chimeric Antigen Receptor (CART-BCMA); Cultured with CytokinesbcmaFor the treatment of multiple myeloma (MM)Autologous T Cells Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen ReceptorOTATACTIVE15-Jul-1512-Jun-1515-Jun-1515-Jun-152015Non-secure email authorized Contacts - amendment 25: Emma Meagher emma@upenn.edu), Michael Milone Michael.Milone@uphs.upenn.edu), Gabriela Plesa gplesa@upenn.edu), Shelly Fehr sfehr@.upenn.edu); David Vaughn - David.Vaughn@uphs.upenn.edu), Barry Brock - bbrock@upenn.edu, Deanna Didonato - deannad@upenn.edu

1IND16550Juno Therapeutics IncMoyer, BentleyAutologous CD3+ T cells (JCAR015) Transduced with Retroviral Vector (293GALV-SFG-1928z) Expressing CD19-specific Chimeric Antigen Receptor (CAR); Following Cyclophosphamide.cd19Treatment for relapsed or refractory B-cell ALL.Autologous CD3+ T cells Transduced with Retroviral Vector (293GALV-SFG-1928z) Expressing CD19-specific Chimeric Antigen Receptor (JCAR015); Retroviral Vector (293GALV-SFG-1928z) Expressing CD19-specific Chimeric Antigen ReceptorOTATHOLD23-Nov-1630-Jun-1530-Jun-1530-Jun-152015Secure email established. Authorized Contact: Bentley Moyer (Phone: 206-582-1646; Fax: 206-682-2219;bentley.moyer@junotherapeutics.com) ; Elizabeth Smith (Office: 206-582-1610; Mobile: 206-719-4366; elizabeth.smith@junotherapeutics.com)

single patientIND16568Grupp MD PhD, Stephan AGrupp MD PhD, Stephan AAutologous T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen Receptorcd19Emergency - Treatment of relapsing and refractory acute lymphoblastic leukemia in a single pediatric patientLentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen Receptor; autologous T cells (collected from the patient)OTATACTIVE6-Jul-156-Jul-156-Jul-156-Jul-157/8/2015 Non-secure email authorized. Authorized Contacts: Dr. Stephan Grupp (GRUPP@email.chop.edu); Laura S. Motley (PHONE: 267-426-6857; Fax: 215-590-3102; Pager: 215-419-2783 (78986); MotleyL@email.chop.edu); Morgan Church (PHONE: 215-590-5476; CHURCHME@EMAIL.CHOP.EDU)

1IND16587Univ of PennsylvaniaMeagher MD, Emma AAutologous CD3+ T cells Transduced with Lentiviral Vector (Anti-CD22BBZeta) Expressing Anti-CD22 scFv with TCR-zeta and 41BB Signaling Domains Chimeric Antigen Receptor (CART22) ; Cultured with Cytokines; Following Lymphodepleting Chemotherapy.cd22For the treatment of Acute Lymphoblastic Leukemia (ALL).Autologous T Cells Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen ReceptorOTATACTIVE14-Aug-1516-Jul-1517-Jul-1517-Jul-152015Permission to communicate via non-secure email with (amendment 24): Emma Meagher - emma@upenn.edu, Katherine Marcucci - kmarcu@upenn.edu, Elizabeth Hexner elizabeth.hexner@uphs.upenn.edu); Shelly Fehr - sfehr@upenn.edu, Ashwini Sabnis - sabnisa@upenn.edu, Deanna Didonato - deannad@upenn.edu

single patientIND16598Mackall MD, Crystal LMackall MD, Crystal LAutologous Peripheral Blood Lymphocytes; Cultured with OKT3 and Interleukin-2; Transduced with Retroviral Vector (PG13-CD19-H3) Expressing Anti CD19 Chimeric Antigen Receptor Gene; Administered Intrathecally.cd19Emergency - Treatment of preB acute lymphocytic leukemia with persistent CNS involvment in a single patient.Autologous Peripheral Blood Lymphocytes; Cultured with OKT3 and Interleukin-2; Transduced with Retroviral Vector (PG13-CD19-H3)OTATACTIVE13-Aug-1529-Jul-1529-Jul-1529-Jul-15Sponsor: Crystal L. Mackall, MD Address:10 Center Drive MSC1104 CRC, Room 1W-3750 City: Bethesda State: MD ZIP: 20892 Contact: DANIEL W LEE Contact Phone: 3014356236 Ext:

single patientIND16618Phillips MD, ChristinePhillips MD, ChristineAutologous T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen Receptor (CART19/CTL019); Following fludarabine and cyclophosphamide as needed.cd19Treatment of relapsed pre-B acute lymphoblastic leukemia (ALL) in a single patient.Autologous T Cells Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen ReceptorOTATWITHDRAWN6-Dec-167-Aug-1511-Aug-1511-Aug-15Secure email established. Authorized Contacts: Dr. Christine Phillips (Christine.Phillips@cchmc.org); Molly Mead (molly.mead@cchmc.org; PHONE: 513-803-7059); Stephanie Edwards (Stephanie.edwards@cchmc.org; PHONE: 513-636-9292); Kristie Stricker (Kristie.stricker@cchmc.org; PHONE: 513-636-3169)

1IND16623UPENNAUTOLOGOUS T CELLS TRANSFECTED WITH MESSENGER RNA EXPRESSING ANTI-CD123 CHIMERIC RECEPTORS; ADMINISTERED USING ELECTROPORATIONcd123AML17-Aug-152015

1IND16658Memorial Sloan-Kettering Cancer CenterHo MD PhD, AlanAutologous T Cells Transduced with Gammaretroviral Vector (SFG-EGFRt-P2A-4H1128z-IRES-IL12) Expressing 4H11 scFv fused to CD28 receptor, TCR CD3-zeta 2, IL12, and EGFRt Chimeric Antigen Receptor (4H1128z/IL12/EGFRt CAR T Cells) in 1% HSA in Plasmalyte A or 20% RIMSO-50, 10% HSA 2% Hetastarch in Plasmalyte A; Administered intravenous and intraperitoneal; Following cyclophosphamide.4H1128z/IL12/EGFRtFor the treatment of fallopian tube, ovarian, and peritoneal cancer.Autologous T Cells Transduced with Gammaretroviral Vector (SFG-EGFRt-P2A-4H1128z-IRES-IL12) Expressing 4H11 scFv fused to CD28 receptor, TCR CD3-zeta 2, IL12, and EGFRt Chimeric Antigen Receptor (4H1128z/IL12/EGFRt CAR T Cells)OTATACTIVE16-Oct-1515-Sep-1516-Sep-1516-Sep-1520159/15/2015 Authorized Contacts: Dr. Alan Ho; Richard Ellis (Authorized countersigner; PHONE:646-735-8044; FAX:646-888-0940; ellisr@mskcc.org)

1IND16664Celgene CorpDoshi, PinkyAutologous Peripheral Blood Mononuclear Cells (PBMCs) Transduced With Anti-BCMA02 CAR Lentiviral Vector Expressing Chimeric Antigen Receptor to Human B Cell Maturation Antigen (Anti-BCMA CAR; bb2121); Cultured with Cytokines; In Cryopreservative Solution; Following Cyclophosphamide and Fludarabine.bcmaFor the treatment of BCMA-expressing multiple myeloma or lymphomas.Lentiviral VectorOTATACTIVE30-Oct-1530-Sep-1530-Sep-1530-Sep-15201501AUG2017: Pinky Doshi, MSc, email: pdoshi@celgene.com

1IND16675Kite Pharma IncSproule PhD, Rizwana FAutologous Peripheral Blood T Cells CD4 and CD8 Selected (Miltenyi Biotec CliniMACS) and IL-2, CD3, and CD28 Activated Transduced with Retroviral Vector (PG13-CD19-H3) Expressing anti-CD19 CD28/CD3-zeta chimeric antigen receptor (KTE-C19 CAR); and Cultured with Cytokines; Following CSF Prophylaxis, Bridging Chemotherapy as needed, Fludarabine, and Cyclophosphamide.cd19For the treatment of patients with Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (r/r ALL).Autologous Peripheral Blood T Cells Transduced with Retroviral Vector (PG13-CD19-H3) Expressing anti-CD19 CD28/CD3-zeta chimeric antigen receptor (KTE-C19 CAR); CliniMACS CD4 Reagent; CliniMACS CD8 Reagent; MACS GMP CD28 pure; MACS GMP CD3 pure; Retroviral Vector (PG13-CD19-H3) Expressing anti-CD19 CD28/CD3-zeta chimeric antigen receptor (KTE-C19 CAR)OTATACTIVE6-Nov-159-Oct-159-Oct-159-Oct-15201510/14/2015 - Non-secure email authorized. Authorized Contacts: Rizwana F Sproule, PhD (Office: (424) 209-1332; Mobile: (805) 276-8586; Fax: (310) 264-0736; rsproule@kitepharma.com); Alex Babayan, PhD (Office: (484) 322-1938; Mobile: (818) 448-1288; Fax: (310) 264-0736; EMAIL: ababayan@kitepharma.com)

1IND16682Center for Cancer ResearchDahut MD, WilliamAutologous T cells Transduced with lentiviral vector (LSIN-47G4-CD828Z) Expressing Human Anti-CD19 Chimeric Antigen Receptor (CAR); Cultured with Cytokines; Following Cyclophosphamide and Fludarabine.cd19For the treatment of advanced B cell malignancies.Autologous Peripheral Blood mononuclear cells; Lentiviral Vector LSIN-47G4-CD828ZOTATACTIVE24-Dec-1528-Sep-1529-Sep-1529-Sep-1520159/28/2015 -Non-secure email authorized in cover letter. Authorized Contacts: NCI Protocol Support Office-include on all emails (nciprotocolsupportoffice@mail.nih.gov); Dr. James Kochenderfer (PHONE: 301-594-5340; kochendj@mail.nih.gov); Nicole Grant (PHONE: 301-272-0476;grantn@mail.nih.gov); R. Rita Misra P:240-276-6123 E:misra@mail.nih.gov

1IND16720Center for Cancer ResearchDahut MD, WilliamAutologous Peripheral Blood Lymphocytes (PBLs) Transduced with Retroviral Vector (PG13-MSGV1-CD27-41BB-CD3zeta (E3)) Expressing Anti-Human CD70 Chimeric Antigen Receptor; Cultured with Cytokines; Following Cyclophosphamide and Fludarabine; Followed by IL-2 Intravenous.cd70For the treatment of patients with CD70 expressing cancers.Retroviral VectorOTATACTIVE31-Mar-1626-Oct-1527-Oct-1527-Oct-1520157/5/2016 - Update non-secure email authorization & Authorized Contacts: Includ on all emails (nciprotocolsupportoffice@mail.nih.gov); William Dahut, MD (dahutw@mail.nih.gov); James C. Yang. M.D. (JamesYang@mail.nih.gov); Mary Ann Toomey, R.N. (PH: 301-435-7507; toomeym@mail.nih.gov); Nicole Grant (grantn@mail.nih.gov)

1IND16758Riddell MD, Stanley RRiddell MD, Stanley RAutologous CD8+ and CD4+ T Cells (Miltenyi CliniMACS) Transduced with Self-Inactivating Lentiviral Vector (R12/S/4-1BB/zeta) Encoding Tyrosine Kinase-like Orphan Receptor 1-specific Chimeric Antigen Receptor (ROR1 CAR); Cultured with Cytokines; Following Chemotherapy; Administered Intravenously.ror1For the treatment of ROR1+ malignancies.Autologous CD8+ and CD4+ T Cells (Miltenyi CliniMACS) Transduced with Self-Inactivating Lentiviral Vector (R12/S/4-1BB/zeta)OTATACTIVE25-Feb-1610-Nov-1523-Nov-1523-Nov-152015Secure email authorized. Authorized Contacts: Dr. Stanley Riddell (P: 206-667-5249; sriddell@fhcrc.org); Susan Lemmon (P: 206-667-1184; F: 206-667-7983; slemmon@fredhutch.org)

1IND16763Riddell MD, Stanley RRiddell MD, Stanley RAutologous CD8+, CD4+ T Cells (Miltenyi CliniMACS) Transduced with Self-Inactivating Lentiviral Vector (ZRX-014-LV) Encoding a CD19-specific Chimeric Antigen Receptor (JCAR014); Cultured with Cytokines; and Durvalumab (MEDI4736); Following Cyclophosphamide and Fludarabine.cd19Treatment of relapsed/refractory B-Cell Non-Hodgkin LympohmaAutologous CD8+, CD4+ T Cells (Miltenyi CliniMACS) Transduced with Self-Inactivating Lentiviral Vector (ZRX-014-LV) Encoding a CD19-specific Chimeric Antigen Receptor (CD19 CAR) and Truncated Epidermal Growth Factor Receptor (EGFRt); Biotinylated anti-CD62L mAb; CiiniMACS-CD14 Reagent; CiiniMACS-CD4 Reagent; CiiniMACS-CD45RA Reagent; Durvalumab (MEDI4736); Dynabeads CD28 CTS; Dynabeads CD3 CTS; Lentiviral Vector Encoding a CD19-specific Chimeric Antigen Receptor (CD19 CAR) and Truncated Epidermal Growth Factor Receptor (ZRX-014-LV); TM-LCLOTATACTIVE23-Dec-1523-Nov-1524-Nov-1524-Nov-152015Secure email established. Authorized Contacts: Dr. Stanley Riddell (sriddell@fhcrc.org); Susan Lemmon (slemmon@fredhutch.org; Phone 206-667-1184; Fax 206-667-7983)

1IND16787Archer PhD, Gary EArcher PhD, Gary EAutologous Peripheral Blood Lymphocytes Transduced with Retroviral Vector (PG13-139-CD8-CD28BZZ) Expressing Anti-Epidermal Growth Factor Receptor, Variant III (EGFRvIII) Chimeric Antigen Receptor (CAR); Following Radiation and Temozolomide.egfrviiiFor the treatment of high grade gliomas.Retroviral VectorOTATACTIVE13-Jan-1611-Dec-1514-Dec-1514-Dec-15201512/11/2015-Non-secure email authorized in cover letter. Authorized Contacts: Dr. Gary Archer (P: 919-684-6977;F: 919-684-9045; gary.archer@duke.edu); Beth Perry (P: 919-684-2695; beth.perry@duke.edu)

withdrawnIND16823iCell Gene TherapeuticsMa MD PhD, YupoAutologous CD8+ and CD4+ T Cells Transduced with Lentiviral Vector (pRSC.CD4.3G) Encoding a CD4-specific Chimeric Antigen Receptor (CD4CAR cells); Cultured with CD3 and IL-2; Following Chemotherapy; Administered Intravenously.cd4For the treatment of relapsed/ refractory CD4+ leukemia and lymphoma as a bridge to bone marrow transplant.OCTGTWITHDRAWN19-Jan-161-Jan-164-Jan-165-Jan-1620161/6/2016-Non-secure email authorized. Authorized Contacts: Dr. Yupo Ma (yupo.ma@icellgene.com); Amelia Firor (Cell: 914-572-7184; amelia.firor@icellgene.com)

emergencyIND16944Waller MD PhD, EdmundWaller MD PhD, EdmundAutologous T Cells Elutriated or Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with Lentiviral Vector Expressing CD19 Chimeric Antigen Receptorcd19Emergency - Treatment of diffuse large B cell lymphomaAutologous T Cells Transduced with Lentiviral Vector Expressing CD19 Chimeric Antigen Receptor (CTL019); Dynabeads CD28; Dynabeads CD3; Human AB serum; Lentiviral Vector Expressing CD19 Chimeric Antigen Receptor; Recombinant Human Proleukin (Aldesleukin)OTATACTIVE31-Mar-1631-Mar-1631-Mar-1631-Mar-16Sponsor: Edmund Waller, MD Address:1365-C Clifton Road, NE City: Atlanta State: GA ZIP: 30322 4/1/2016 Non-secure email authorized.Authorized Contacts: Edmund Waller (P: 404-727-4995; F: 404-772-9995; ewaller@emory.edu); Dr. Cohen (jonathon.cohen@emory.edu); Dr. Amelia Langston (p: 404-778-4236; F: 404-778-5530; alangst@emory.edu); Ki-Ling Suen (P: 404-778-2477; ki-ling.suen@emory.edu); Kim Nguyen (P: 404-778-5680; kim.t.nguyen@emory.edu).

1IND17036Bellicum Pharmaceuticals IncFrench, MarthaAutologous Peripheral Blood T cells (BPX-601) Transduced with Retroviral Vector (BPZ-1004; SFG-dM-iMC-T2A-PSCA (A11) scFV-CD34e-CD8stm-CD3zeta) Expressing Prostate Stem Cell Antigen-Specific Chimeric Antigen Receptor (anti-PSCA CAR) and an Inducible Co-Stimulatory Domain From MyD88 and CD40 (iMC); Following Chemotherapy; Followed by AP1903.pscaFor the treatment of non-resectable pancreatic cancerAP1903 (Rimiducid); Autologous Peripheral Blood T Cells Transduced with Retroviral Vector (BPZ-1004) Expressing Prostate Stem Cell Antigen-Specific Chimeric Antigen Receptor (anti-PSCA CAR) and an Inducible Co-Stimulatory Domain From MyD88 and CD40 (iMC); MACS GMP Recombinant Human IL-15; MACS GMP Recombinant Human IL-7; Retroviral Vector (BPZ-1004) Expressing Prostate Stem Cell Antigen-Specific Chimeric Antigen Receptor (anti-PSCA CAR) and an Inducible Co-Stimulatory Domain From MyD88 and CD40 (iMC); Solutol HS 15; anti-CD28 antibody (MACS? GMP CD28 pure); anti-CD3 antibody (MACS GMP CD3 pure)OTATACTIVE7-Jul-163-Jun-167-Jun-167-Jun-162016Secure email established. Authorized Contacts: Martha French (P: 832-384-1119; F: 281-768-7698; mfrench@bellicum.com); Maryam Ansari (P: 346-772-3263; F:832-384-1550; mansari@bellicum.com); Annemarie Moseley (P:832-384-1108; amoseley@bellicum.com)

single patientIND17073Gardner MD, RebeccaGardner MD, RebeccaAutologous CD4+/CD8+T Cells Activated with CD4/CD8 Microbead Mix; Transduced with Lentiviral Vector (SCRI-CAR19v1) Expressing CD19-Specific Chimeric Antigen Receptor and EGFRt; Cultured with Interleukin-2 and Interleukin-15.cd19Treatment of a single patient with Acute Lymphoblastic Leukemia (ALL).Autologous Peripheral Blood T Cells Transduced with Lentiviral Vector (ZRX-014-LV) Encoding a CD19-specific Chimeric Antigen Receptor (CD19 CAR); CD3/CD28 CTS Dynabeads; Lentiviral Vector Encoding a CD19-specific Chimeric Antigen Receptor (ZRX-014-LV)OTATACTIVE18-Jul-1630-Jun-165-Jul-165-Jul-16Secure email established. Authorized Contact: Rebecca Gardner, MD (P: 206-987-2106; Pager: 206-987-2000; rebecca.gardner@SeattleChildrens.org); Zahid Hossain (P: 206-884-4081; zahid.hossain@seattlechildrens.org); Michael Jensen, MD (P: 206-987-1241; michael.jensen@seattlechildrens.org)

single patientIND17157Univ of PennsylvaniaSchuster MD, StephenAutologous T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen Receptorcd19Single patient treatment of primary refractory diffuse large Bcell lymphomaAutologous T Cells Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen ReceptorOTATWITHDRAWN12-Jan-1719-Sep-1621-Sep-1621-Sep-16Permisison to communicate using e-mail with: Stephen Schuster, and Kristy Walsh

1IND17178Univ of Pennsylvania Medical CenterMeagher MD, Emma AAutologous CD4+ and CD8+ T Cells Transduced with Lentiviral Vector Expressing Mesothelin-Specific Chimeric Antigen Receptor (CART-meso); Administered IntravenouslymesoMesothelin Expressing CancersT Cells, Autologous, Transfected With Chimeric Anti-Mesothelin Immunoreceptor Gene (Messenger RNA)OTATACTIVE3-Nov-163-Oct-165-Oct-165-Oct-162016Amendment 3 - Permission to communicate using e-mail with: Emma Meagher - emma@exchange.upenn.edu, Gabriela Plesa - gplesa@exchange.upenn.edu, Bruce J. Giantonio - Bruce.Giantonio@uphs.upenn.edu, Deanna DiDonato - deannad@exchange.upenn.edu, Shelly Fehr - sfehr@exchange.upenn.edu, Aswini Sabnis - sabnisa@upenn.edu

1IND17231Univ of PennsylvaniaMeagher MD, Emma AAutologous T Cells Transduced with Lentivirus Vector Expressing Transforming Growth Factor Beta Receptor (TGF?RDN) and Chimeric Antigen Receptor (CAR); Administered IntravenouslypsmaCastrate Resistant Prostate CancerOTATACTIVE14-Dec-1610-Nov-1614-Nov-1614-Nov-162016Permission to communicate via non-secure e-mail with: Emma Meagher - emma@exchange.upenn.edu

1IND17246Turtle MBBS PhD, CameronTurtle MBBS PhD, CameronAutologous T Cells Transduced with Lentiviral Vector CD19-Targeted Chimeric Antigen Receptor (CAR)-Modified T cells bearing a Human Binding Domain (huJCAR014)cd19Treatment for relapse or refractory B cell non-Hodgkins lymphoma and acute lympholytic leukemiaAllogeniec T Cells Transduced with Lentiviral Vector CD19-Targeted Chimeric Antigen Receptor (CAR)-Modified T cells bearing a Human Binding Domain (huJCAR014)OTATACTIVE22-Dec-1621-Nov-1622-Nov-1622-Nov-162016

1IND17251Memorial Sloan-Kettering Cancer CenterHo MD PhD, AlanAutologous T-cells Transduced with Retroviral Vector Expressing EGFRt/1928z/4-1BBL Chimeric Antigen Receptorcd19Relapsed or Refractory Chronic Lymphocytic LeukemiaOTATACTIVE28-Dec-1625-Nov-1628-Nov-1628-Nov-162016Authorized unsecure email contact: Richard Ellis, Regulatory Compliance, email: ellisr@mskcc.org

1IND17264Center for Cell and Gene TherapyBrenner MD PhD, Malcolm KAutologous glypican-3 specific chimeric antigen expressing T cells (GPC3-CAR T cells)gp-3Hepatocellular carcinoma (HCC)Autologous Peripheral Blood; IL-7 and IL-15; SFG.GP3.CAR.41BBOTATACTIVE24-May-177-Nov-161-Dec-161-Dec-162016Authorized contacts: Malcolm Brenner, MD (mbrenner@bcm.edu ) 832-824-4671 Helen Heslop, MD (hheslop@bcm.edu ) 832-824-4671 Bambi Grilley, RPh (grilley@bcm.edu ) 832-824-3893 Stephen Gottschalk, MD (smg@bcm.edu) 832-824-4179

1IND17383Fred Hutchinson Cancer Research CenterHedin, LaceyAutologous T-cells Transduced with Lentiviral Vector Expressing CD20-specific Chimeric Antigen Receptor Genecd20Treatment of Relapsed or Refractory B Cell Non-Hodgkin LymphomasOTATACTIVE29-Mar-1724-Feb-1727-Feb-1727-Feb-172017

1IND17400Bluebird Bio IncBhandarkar MS, RamolaAutologous T Lymphocyte-enriched Cells Tranduced with Lentiviral Vector Encoding a Chimeric Antigen Receptor Targeting B Cell Maturation Antigen (anti-BCMA02 CAR); Cultured with a Phosphatidylinositol 3-kinase InhibitorbcmaTreatment of multiple myeloma and lymphomaOTATACTIVE22-Apr-1723-Mar-1723-Mar-1723-Mar-172017Expected document arrival: 27-MAR-2017 Sponsor: Contact: Ramola Bhandarkar (email: Rbhandarkar@bluebirdbio.com); Anne-Virginie Eggimann 339-499-9320 (email: aveggimann@bluebird.com) Ext: Secure email established.

1IND17428Univ of TexasBuzdar MD, AmanAutologous T-cells Transduced with Lentiviral Vector Expressing CD33-Specific Chimeric Antigen Receptor Gene (CD33-CAR-T cells)cd33Patients with Relapsed or Refractory CD33-Positive Acute Myeloid LeukemiaCD3+ T cells genetically modified using a lentiviral vector (INXN-2006) to co-express a CD33-specific CAR and the HER1t depletion markerOTATACTIVE28-Apr-1729-Mar-1731-Mar-1731-Mar-172017

1IND17461Center for Cell and Gene TherapyHeslop MD, Helen EAutologous T-Cells Transduced with Retroviral Vectors Expressing a second Generation Chimeric Antigen Receptor CD5.CARcd5Relapsed/refractory CD5+ T cell malignanciesOTATACTIVE25-May-1719-Apr-1725-Apr-1725-Apr-172017

1IND17484Mackall MD, Crystal LBirkett, NealAutologous T-cells transduced with bivalent lentiviral vector (CD19/CD22.BB.z) chimeric antigen receptor (CAR); following fludarabine and cyclophosphamidecd19 + cd22Recurrent or refractory B Cell malignanciesAutologous Peripheral Blood Lymphocyte; Lentiviral Vector (CD19-CD22.BBz)OTATACTIVE7-Jun-175-May-178-May-178-May-172017secure email established. Authorized contact: Neal Birkett, directly at 650-723-6456 (email: nbirkett@stanford.edu), send urgent email: CCTO-Regulatory@Stanford.edu and Lee Doherty at 650-736-0176.

1IND17501CelgeneCorbett PhD MBA, Wendy LAutologous CD4+/CD8+ T Cells Expressing CD19 Chimeric Antigen Receptor(JCAR017)cd19Relapsed/refractory aggressive B-cell non-Hodgkin lymphoma (NHL)OTATACTIVE7-Jul-179-Jun-179-Jun-179-Jun-172017Expected document arrival: 05-JUN-2017 Sponsor: Celgene Corporation Address:86 Morris Avenue City:Summit NJ 07901 Contact: Wendy Corbett 9082190734 Ext:

1IND17518Nirvah ShahAUTOLOGOUS T-CELLS ENGINEERED TO CONTAIN AN ANTI-CD19 AND ANTI-CD20 SCFV COUPLED TO CD3 ZETA AND 4-1BB SIGNALING DOMAINS (CLINIMACS PRODIGY)cd19 + cd20Patients with relapsed and/or refractory CD19 or CD20 positive B cell malignancies26-May-172017

1IND17521Maxcyte IncDoerfler, DougAutologous Peripheral Blood Leukocytes, Transfected via Electroporation to Express Human Mesothelin Chimeric Antigen Receptor mRNAmesoPlatinum Resistant High Grade Serous Adenocarcinoma of the Ovary, Primary Peritoneum, or Fallopian Tube or Peritoneal MesotheliomaMCY-M11OTATHOLD13-Dec-1717-Nov-1717-Nov-1717-Nov-172017Permission to communicate with Doug Doerfler - dougd@maxcyte.com, Kathy Wekselman - kwekselman@ctifacts.com, Stephanie Makepeace - smakepeace@ctifacts.com and Debra Bowes - dbowes@maxcyte.com

MFMF217526Bluebird Bio IncFurlotte, NikoleAnti-BCMA02 Chimeric Antigen Receptor (CAR) Lentiviral Vector and its starting materialsmanufacture of productOTATACTIVE7-Jun-177-Jun-177-Jun-177-Jun-17Expected document arrival: 30-JUN-2017 Sponsor: bluebird bio, Inc Address:60 Binney Street City:Cambridge MA 02142 Contact: Anne-Virginie Eggimann 3394999320 Ext:

1IND17619Kite Pharma IncSproule PhD, Rizwana FAutologous Anti-BCMA CAR TCells, transduced with a self-inactivating (SIN) lentiviral vector encoding an anti-B-cell maturation antigen (BCMA) CD28/CD3-zeta chimeric antigen receptor (KITE-585)bcmaFor the treatment of patients with relapsed/refractory multiple myeloma (RRMM)OTATPENDING4-Aug-174-Aug-174-Aug-174-Aug-172017Expected document arrival: 07-AUG-2017 Sponsor: Kite Pharma Address:2225 Colorado Avenue City:Santa Monica CA 90404 Contact: Farnoosh Zamani 9294777382 Ext:

1IND17715Green MD, DamianGreen MD, DamianAutologous T-cells (CD4 and CD8) transduced with self-inactivating (SIN) lentiviral vector to express a B-cell maturation agent (BCMA) - specific chimeric antigen receptor (CAR).bcmaFor patients with advanced multiple myeloma (MM) with a confirmed diagnosis of BCMA+ MMBCMA CAR T cell Product; BCMA-4-1BB-CD3 -EGFRt CAR lentivirusOTATACTIVE13-Oct-1711-Sep-1713-Sep-1713-Sep-172017

1IND17731Amgen IncPathak, VandanaAutologous, CAR-T cells targeting delta-like ligand 3 (DLL3), transduced with third-generation SIN HIV-1 lentiviral vector, AMG 119DLL3Relapsed/Refractory Small Cell Lung Cancer293FT-K640 Lentiviral Vector; Autologous CAR T cells expressing delta like ligand 3 (DLL3)OTATPENDING19-Dec-1719-Dec-1719-Dec-1719-Dec-172017Expected document arrival: 01-DEC-2017 Sponsor: AMGEN INC. Address:One Amgen Center Drive City:Thousand Oaks CA 91320 Contact: Vandana Pathak 8053132864 Ext:

1IND17735Cartesian Therapeutics, Inc.Kalayoglu, MuratAutologous mRNA-transfected CD8+ T-cells transiently expressing a Chimeric Antigen Receptor for B-Cell Maturation Antigen; IV Administration (Descartes-08)bcmaMultiple MyelomaOTATACTIVE1-Dec-171-Nov-171-Nov-171-Nov-172017Expected document arrival: 02-OCT-2017 Sponsor: Cartesian Therapeutics, Inc. Address:12111 Parklawn Dr., Suite 245 City:Rockville MD 20852 Contact: Maureen Merrifield 2819146228 Ext:

1IND17744Eureka Therapeutics IncNejadnik MD, BijanAutologous T cells transduced with lentiviral vector expressing ARTEMIS Chimeric Antigen Receptor Targeting CD19cd19relapsed/refractory CD19+ Non-Hodgkin's lymphomaOTATACTIVE21-Nov-1727-Oct-1727-Oct-1727-Oct-172017Expected document arrival: 13-OCT-2017 Sponsor: Eureka Therapeutics, Inc. Address:5858 Horton Street, Suite 362 City:Emeryville CA 94608 Contact: Vivien Chan 5106547045 Ext:

1IND17748Juno Therapeutics IncMoyer, BentleyAutologous CD4+ and CD8+ T Cells (JCARH125) Transduced with Replication-Incompetent, Self-Inactivating (SIN) Lentiviral Vector(v20008) encoding Chimeric Antigen Receptor (CAR-T) and B-Cell Maturation Antigen (BCMA)bcmaImmunotherapy for relapsed or refractory multiple myelomaAutologous CD4+ and CD8+ T cells Transduced with Self-Inactivating (SIN) Lentiviral Vector (v20008) Expressing CD19-specific Chimeric Antigen Receptor (CAR) (JCAR0125)OTATACTIVE29-Dec-171-Dec-171-Dec-171-Dec-172017bentley.moyer@junotherapeutics.com Expected document arrival: 08-DEC-2017 Sponsor: Juno Therapeutics, Inc Address:400 Dexter Avenue North, Suite 1200 City:Seattle WA 98109 Contact: Bentley Moyer 2065821646 Ext:

1IND17764National Cancer InstituteDahut MD, WilliamPhase 1 Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults with Recurrent and Refractory CD19/CD22-expressing B Cell Malignancies.cd19/cd22Recurrent or refractory, CD19/CD22-expressing, B cell acute lymphoblastic leukemia or lymphomaOTATACTIVE6-Dec-176-Nov-176-Nov-176-Nov-172017Expected document arrival: 25-OCT-2017 Sponsor: Center for Cancer Research, NCI Address:10 Center Drive, Room 3-2571 City:Bethesda MD 20892 Contact: Hilda Grabczewski 2402766002 Ext:

1IND17765Lineberger Comprehensive Cancer CenterSerody MD, Jonathan SAutologous Peripheral Blood Mononuclear Cells Activated with anti-CD3 and anti-CD28, Transduced with Retroviral Vector (SFG.CAR.CD138hCD8a.4-1BBz) Expressing CD138 Chimeric Antigen Receptor (CAR138 T-cells)cd138Treatment of Multiple MyelomaRetrovirus Expressing CD138 CAR (SFG.CAR.CD138hCD8a.4-1BBz); T cells Expressing CD138 Chimeric Antigen Receptor (CAR138 T cells)OTATACTIVE9-Nov-176-Oct-1711-Oct-1711-Oct-172017

1IND17794NantKwest IncNolasco, AleeceNK-92/5.28.z (HER2.taNK), Allegeneic clonal cell line generated from NK-92 cell line expressing a second generation chimeric antigen receptor (CAR), administered by intravenous (IV) infusion.Her2Metastatic or Locally Advanced HER2-positive Solid TumorsOTATHOLD5-Jan-188-Dec-178-Dec-178-Dec-172017Expected document arrival: 8-DEC-2017 Sponsor: NantKwest, Inc Address:9920 Jefferson Blvd City:Culver City CA 90232 Contact: Aleece Nolasco 3104057549 Ext:

1IND17815Center for Cell and Gene TherapyBrenner MD PhD, Malcolm KAutologous Natural Killer T cells transduced with a retroviral vector expressing GD2-specific chimeric antigen receptor and interleukin-15 (GD2.CAR NKT cells)gd-2Relapsed and Refractory NeuroblastomaOTATACTIVE7-Dec-1729-Sep-177-Nov-177-Nov-172017

1IND17849Univ of Pennsylvania Medical CenterMeagher MD, Emma AAutologous T cells Transduced with Lentiviral Vector (AntiBCMAbbz human) Expressing B-cell Maturation Antigen (BCMA)-specific Chimeric Antigen Receptor (CART-BCMA) with or without Autologous CD3+ T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with self-inactivating (SIN) Lentiviral Vector (CD19bbz-human Lot# 060713S12) Expressing Humanized CD19 Chimeric Antigen Receptor (huCART19); and chemotherapybcma/cd19Treatment of multiple myelomaAutologous CART-BCMA; Autologous huCART19; Self-Inactivating lentivirus vector to express CAR of second generation specific to BCMAOTATACTIVE21-Dec-1715-Nov-1721-Nov-1721-Nov-172017

1IND17857Seattle Children's Research InstituteJensen MD, Michael CAutologous T cells Selected with CliniMACS CD8 and CD4 reagent systems Transduced with A Self-Inactivating Lentiviral Vector Expressing HER-2-specific Chimeric Antigen Receptor and truncated EGF ReceptorHer2Treatment of Her2 positive recurrent/refractory pediatric brain tumors.OTATACTIVE22-Dec-1722-Nov-1724-Nov-1724-Nov-172017Email authorized: michael.jensen@seattlechildrens.org

117890HER2Recurrent or refractory malignat gliomaAUTOLOGOUS T CELLS TRANSDUCED WITH LENTIVIRAL VECTOR EXPRESSING HER2 SPECIFIC CHIMERIC ANTIGEN RECEPTOR AND TRUNCATED CD19T

single patientIND17893Grupp MD PhD, Stephan AGrupp MD PhD, Stephan AtisagenlecleucelEmergency - Yes, for the treatment of relapsed refractory ALLAutologous T Cells Transduced with Lentiviral Vector Expressing CD19 Chimeric Antigen Receptor (CTL019); Dynabeads CD3; Lentiviral Vector Expressing CD19 Chimeric Antigen ReceptorOTATACTIVE23-Dec-1723-Dec-1723-Dec-1723-Dec-17Sponsor: Stephan Grupp Address:Children's Hospital of Philadelphia 3501 Civic Center Blvd, CTRB 3006 City: Philadelphia State: PA ZIP: 19104 Contact: STEPHAN GRUPP Contact Phone: 2155905476 Ext:

single patientIND17901Univ of TexasBuzdar MD, Amantisagenlecleucel (antiCD19 CAAR T cell)Emergency - need approval to proceed with manufacturingAutologous T Cells Transduced with Lentiviral Vector Expressing CD19 Chimeric Antigen Receptor (CTL019); Dynabeads CD3; Lentiviral Vector Expressing CD19 Chimeric Antigen ReceptorOTATACTIVE26-Dec-1726-Dec-1726-Dec-1726-Dec-17Permisison to communiate with: Stella Tsai - swtsai@mdanderson.org, Jose Miguel Arriaga - jmarriaga@mdanderson.org, Faiza Chohan - FKChohan@mdanderson.org, Sean O'Connor - soconnor@mdanderson.org and Felicia Nica - alinan@mdanderson.org

93

Active CAR Tcells

TypeSub IdyearSponsorContactTitletargetProposed UsehemeProduct

1IND132662007Memorial Sloan-Kettering Cancer CenterHo MD PhD, AlanAutologous CD3+ T-cells Transduced with Retroviral Vector (SFG-1928z, MSKCC) Expressing CD19 Chimeric Antigen Receptor;; Cultured with Interleukin-2CD1945Treatment of purine analogue refractory chronic Lymphocytic Leukemia1Aldesleukin [Proleukin]; Autologous CD3+ T-cells Transduced with CD19 chimeric antigen receptor gene (Retroviral Vector SFG-1928z, MSKCC); Cultured with Interleukin-2

1IND132962007Center for Cell and Gene TherapyHeslop MD, Helen EAutologous PBMC Cultured w/IL-2 and OKT3; Transduced w/Retroviral Vector (CD19-CAR) Expressing CD19 Chimeric Antigen Receptor Gene; and Autologous PBMC Cultured w/IL-2 and OKT3; Transduced w/Retroviral Vector (CD19-CD28-CAR) Expressing CD19-CD28 Chimeric Antigen Receptor GeneCD19Treatment of B-Cell non Hodgkin's lymphoma and Chronic lymphocytic leukemia1Aldesleukin [Proleukin]; MoAb, OKT3, Murine, to CD3+ [Orthoclone OKT3]; Peripheral Blood Mononuclear Cells (Autologous) Transduced with CD19 Chimeric Antigen Receptor Gene (Retroviral Vector CD19-CAR); Peripheral Blood Mononuclear Cells (Autologous) Transduced with CD19-CD28 Chimeric Antigen Receptor Gene (Retroviral Vector CD19-CD28-CAR)

1IND138712008Center for Cancer ResearchDahut MD, WilliamAutologous Peripheral Blood Lymphocytes Cultured with OKT3 and Interleukin-2; Transduced with Retroviral Vector PG13-CD19-H3, NCI) Expressing Anti-CD19 Chimeric Antigen Receptor Gene; and Interleukin-2CD19Treatment of advanced B-cell malignancies1CliniMACS CD19 reagent system; Interleukin-2; Aldesleukin; MoAb, OKT3, Murine, to CD3+ [Orthoclone OKT3]; Peripheral Blood Lymphocytes, Autologous, Transduced with Anti-CD19 Chimeric Antigen Receptor Gene (Retroviral Vector PG13-CD19-H3)

1IND139022008Center for Cell and Gene TherapyBrenner MD PhD, Malcolm KAutologous PBL Cultured with OKT3, Transduced with Retroviral Vector (SFG.CD19CAR-28zeta) Expressing CD19 Chimeric Antigen Receptor Gene; and Autologous, EBV Specific CTL Cultured with IL-2, Transduced with Retroviral Vector (SFG.CD19CARzeta) Expressing CD19 Chimeric Antigen Receptor GeneCD19Treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia1Autologous PBL Transduced with Retroviral Vector (SFG.CD19CAR-28zeta) Expressing CD19 Chimeric Antigen Receptor Gene; Autologous, EBV Specific CTL Transduced with Retroviral Vector (SFG.CD19CARzeta) Expressing CD19 Chimeric Antigen Receptor Gene

1IND139582009Center for Cell and Gene TherapyBrenner MD PhD, Malcolm KAutologous Peripheral Blood Mononuclear Cells co-cultured with Autologous Dendritic Cells Transduced with Adenovirus Vector (Ad5f35CMVpp65, CCGT) Expressing CMVpp65 then Expanded with LCL Transduced with Adenovirus Vector (Ad5f35CMVpp6, CCGT) Expressing CMVpp65; Transduced with Retroviral Vector (SFG.CD19CAR28) Expressing CD19 Chimeric Antigen Receptor GeneCD19Treatment of relapsed high-risk B-cell Acute Lymphoblastic Leukemia post Hemopoietic Stem Cell Transplant1Autologous Peripheral Blood Mononuclear Cells co-cultured with Autologous Dendritic Cells Transduced with Adenovirus Vector (Ad5f35CMVpp65, CCGT) Expressing CMV; LCL Transduced with Adenovirus Vector (Ad5f35CMVpp6, CCGT) Expressing CMVpp65; Transduced with Retroviral Vector (SFG.CD19CAR28) Expressing CD19

1IND139602009Univ of PennsylvaniaMeagher MD, Emma AAutologous T Cells Cultured with Anti-CD3 and Anti-CD28 Coated Magnetic Beads; Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen ReceptorCD19Treatment of refractory CD19+ leukemia and lymphoma ADDITIONAL CONTACTS: Shelly Fehr (215-662-4639; sfehr@exchange.upenn.edu)1Autologous T Cells Transduced with Lentiviral Vector (CART-19, Lentigen) Expressing CD19 Chimeric Antigen Receptor

1IND139652009Center for Cell and Gene TherapyBrenner MD PhD, Malcolm KAutologous Peripheral Blood Mononuclear Cells Cultured with OKT3 and Interleukin-2 and Transduced with Retroviral Vector (pG13.SFG.CAR-K, CAGT VPF) Expressing Kappa-Light Chain Chimeric Antigen Receptor GeneCD19Treatment of non-Hodgkin lympoma and chronic lymphocytic leukemia1Autologous Peripheral Blood Mononuclear Cells Transduced with Retroviral Vector (pG13.SFG.CAR-K, CAGT VPF)

1IND140362009Center for Cell and Gene TherapyGottschalk MD, StephenAutologous EBV-specific CTL Transduced with Retroviral Vectors (SFG.TGFbetaR11deltacyt) Expressing Dominant Negative TGFbeta Receptor II Gene and (SFG.FP5.CD28.zeta) Expressing the HER2 Chimeric Antigen Receptor Gene; Expanded with Interleukin-2Her25Treatment of HER2 positive lung cancerAutologous EBV-specific CTL Transduced with Retroviral Vector (SFG.TGFbetaR11deltacyt) Expressing Dominant Negative TGFbeta Receptor II Gene; Autologous EBV-specific CTL Transduced with Retroviral Vector SFG.FP5.CD28.zeta) Expressing the HER2 Chimeric Antigen Receptor Gene

1IND140502009Center for Cell and Gene TherapyHeslop MD, Helen EAutologous EBV-specific CTL Transduced with Retroviral Vectors (HER2.CAR.CD28.zeta) Expressing the HER2 Chimeric Antigen Receptor GeneHer2treatment of advanced HER2 positive osteosarcomaAutologous EBV-specific CTL Transduced with Retroviral Vectors (HER2.CAR.CD28.zeta) Expressing the HER2 Chimeric Antigen Receptor Gene

1IND141722009Center for Cancer ResearchDahut MD, WilliamAllogeneic Pheripheral Blood Lymphocytes Transduced with Retroviral Vector PG13-CD19-H3 Expressing anti-CD19 Chimeric Antigen Receptor GeneCD19Treatment of recurrent or persistent B-Cell malignancies after allogeneic stem cell transplantation1Aldesleukin [Proleukin]; MoAb, OKT3, Murine to CD3+[Orthoclone OKT3]/MoAb, Murine to CD28+, Magnetic Bead; Peripheral Blood Lymphocytes, Autologous, Transduced with Anti-CD19 Chimeric Antigen Receptor Gene (Retroviral Vector PG13-CD19-H3)

1IND141932009Univ of TexasBuzdar MD, AmanAutologous CD19 Specific T cells Transduced with DNA Plasmid Vectors (Sleeping Beauty System) Expressing Chimeric Antigen Receptor; Co-cultured with Gamma-irradiated K562 Tumor Cell Line Transduced with Lentiviral Vectors; with or without Interleukin-2CD19Treatment for B-lymphoid malignancy relapse following autologous HSCT1Autologous CD19 Specific T cells Derived from PBMC Transduced with Sleeping Beauty Plasmid DNA; CliniMACS CD56 Reagent System; Interleukin-2 (Proleukin)

1IND144032010Center for Cell and Gene TherapyHeslop MD, Helen EAutologous Peripheral Blood Mononuclear Cells co-cultured with Autologous Dendritic Cells Transduced with Adenovirus Vector (Ad5f35CMVpp65, CCGT) Expressing CMVpp65 then Expanded with LCL Transduced with Adenovirus Vector (Ad5f35CMVpp6, CCGT) Expressing CMVpp65; Autologous EBV-specific CTL Transduced with Retroviral Vector (HER2.CAR.CD28.zeta) Expressing the HER2 Chimeric Antigen Receptor GeneHer2Treatment of Glioblastoma MultiformePeripheral Blood Mononuclear Cells, Autologous,; Dendritic C