The Role of mTOR in Cancer Etiology and Treatment

Based on presentations from the44th Annual Meeting of the

American Society of Clinical Oncology (ASCO)May 30-June 3, 2008

Chicago, Illinois

MCL confirmed locally

Relapsed/refractory to2-7 prior therapies

Required:

• Rituximab

• Anthracycline

• Alkylating agent

R

A

N

D

O

M

I

Z

A

T

I

O

N

Temsirolimus 175 mg q3w then 75 mg qw

Temsirolimus 175 mg q3w then 25 mg qw

Investigator’s choice

single agent*

Temsirolimus treatment to continue until progression, death or unacceptable toxicity

Adapted from Hess et al. ASCO 2008, abstract 8513.

Study Design

*Protocol specified (n): Gemcitabine i.v. (22), fludarabine i.v., oral (14), chlorambucil oral (3), cladribine i.v. (3), etoposide i.v. (3), cyclophosphamide oral (2)

*Approved additions (n): Thalidomide oral (2), vinblastine i.v. (2)alemtuzumab i.v. (1), lenalidomide oral (1)

Period Temsirolimus 175/75n=54

Temsirolimus 175/25n=54

Week 1-3 Mean dose intensity, mg/wk Mean relative dose intensity

 1300.74

 1220.70

Week 4 – end of treatment Mean dose intensity, mg/wk Mean relative dose intensity

 52

0.69

 21

0.86

Overall exposure Mean total exposure, mg Mean dose intensity, mg/wk Mean relative dose intensity

 125384

0.74

75759

0.80

Dose Administration and Exposure

Adapted from Hess et al. ASCO 2008, abstract 8513.

  Temsirolimus 175/75n=54

Temsirolimus 175/25n=45

Investigator’s choicen=50

Median PFS, months 4.8 3.5 2.0

95% CI

P value vs. IC

Hazard ratio

95% CI

4.2-7.4

0.0026

0.47

0.28-0.77

2.0-6.2

0.0464

0.61

0.37-1.00

1.6-2.5

Date of data cutoff: 19 July 2007 (independent assessment)

 

Progression-free Survival (ITT) Excluding Patients with Blastoid Histology

Adapted from Hess et al. ASCO 2008, abstract 8513.