687P - Updated efficacy, biomarker, and exposure-response data from a phase 2 study of rilotumumab (R) plus epirubicin, cisplatin, and capecitabine (ECX) i...

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Oesophageal Cancer
Gastric Cancer
Translational Research
Presenter Irina Davidenko
Authors I. Davidenko1, T. Iveson2, R.C. Donehower3, S. Tjulandin4, A. Deptala5, Y. Jiang6, M. Zhu7, K.S. Oliner8, S. Dubey9, E. Loh9
  • 1Clinical Oncology Dispensary #1, 350040 - Krasnodar/RU
  • 2Medical Oncology, Southampton General Hospital, Southampton/UK
  • 3Cancer Center, Johns Hopkins, Baltimore/US
  • 4Clinical Pharmacology And Chemotherapy, Russian Cancer Research Center, Moscow, Moscow/RU
  • 5Department Of Oncology And Hematology, Central Clinical Hospital MSWIA-WarsawMedical University of Warsaw, PL-02-507 - Warsaw/PL
  • 6Global Biostatistical Science, Amgen Inc., Thousand Oaks/US
  • 7Pharmacokinetics & Drug Metabolism, Amgen Inc., Thousand Oaks/US
  • 8Molecular Sciences - Ivd, Amgen Inc., Thousand Oaks/US
  • 9Oncology, Amgen Inc., South San Francisco/US

Abstract

Background

R (AMG 102) is an investigational, fully human monoclonal antibody to hepatocyte growth factor/scatter factor, the MET receptor ligand. Safety and efficacy of a placebo-controlled, double-blind, randomized phase 2 study of R + ECX in G/EGJ cancer from a 12.5-month (mo) follow up were previously reported (Iveson et al, Eur J Cancer. 2011; 47(suppl 1):S443. abstract 6.504). Updated data from a 21.7-mo follow up are presented.

Methods

Eligibility included unresectable, locally advanced or metastatic G/EGJ adenocarcinoma; ECOG PS ≤1; and no prior systemic therapy for this disease. Patients (pts) were randomized 1:1:1 to ECX (50 mg/m2 IV day 1, 60 mg/m2 IV day 1, 625 mg/m2 BID orally days 1–21, respectively) + R 15 mg/kg (Arm A); R 7.5 mg/kg (Arm B); or placebo (Arm C) IV day 1 every 3 weeks. Overall survival (OS) and progression-free survival (PFS) were evaluated. MET protein was measured in archival tumor samples by IHC. R serum concentrations for all pts were measured. Individual R steady-state Cminss were estimated with a population PK model.

Results

121 pts (Arms A/B/C: 40/42/39) were randomized Oct 2009 to June 2010. See table for data (Jan 16, 2012 cutoff).

Conclusions

Within the context of a small, randomized phase 2 study, R + ECX improved outcomes in G/EGJ cancer pts. The treatment effect was strongest in pts with high MET tumors and high R exposure. Consistent with previously reported data, these results show continued separation of Arm A + B vs C beyond 16 mo. A planned phase 3 study will test the safety and efficacy of R + ECX in MET-positive G/EGJ cancer.

Table: 687P

Median OS (80% CI), mo OS HR (95% CI) Median PFS (80% CI), mo PFS HR (95% CI)
All pts Arm A + B n = 82 10.6 (9.5–12.0) 5.7 (5.1–6.9)
Arm C n = 39 8.9 (5.7–10.6) 4.2 (3.7–4.6)
Arm A + B vs C 0.70 (0.45–1.09) 0.60 (0.39–0.91)
METH* Arm A + B n = 27 11.5 (9.2–12.1) 6.9 (5.5–7.5)
Arm C n = 11 5.7 (4.5–10.4) 4.6 (3.7–5.2)
Arm A + B vs C 0.34 (0.15–0.78) 0.44 (0.20–0.96)
METH*, RH Arm A + B n = 13 17.6 (13.3–21.0) 10.7 (6.9–15.3)
Arm C n = 11 5.7 (4.5–10.4) 4.6 (3.7–5.2)
Arm A + B vs C 0.18 (0.06–0.52) 0.19 (0.06–0.57)

*Pts with >50% tumor cells MET positive, Pts with R median Cminss ≥ 94 µg/mL.

Disclosure

T. Iveson: Dr. Iveson received research funding and travel payment from Amgen Inc.

Y. Jiang: Dr. Jiang is an employee of and owns stock in Amgen Inc.

M. Zhu: Dr. Zhu is an employee of and owns stock in Amgen Inc.

K.S. Oliner: Dr. Oliner is an employee of and owns stock in Amgen Inc.

S. Dubey: Dr. Dubey is an employee of and owns stock in Amgen Inc.

E. Loh: Dr. Loh is an employee of and owns stock in Amgen Inc.

All other authors have declared no conflicts of interest.