A Phase 1b/2 Study of AMG 655 in Combination With Paclitaxel and Carboplatin for the First-Line Treatment of Advanced Non-Small Cell Lung Cancer

Summary

Part 1 is complete. Part 2 is a multi-center, randomized, double-blind, placebo-controlled, phase 2 segment that will commence upon identification of the maximum tolerated dose in part 1. The Primary objective of Part 2 of the study is to estimate efficacy in combination with carboplatin and paclitaxel. Subjects will be randomized at a 1:1:1 ratio to 1 of 3 treatment arms. Subjects in each of the 3 arms will receive up to 6 cycles of paclitaxel/carboplatin (at the same dose and schedule in part 1) in combination with either AMG 655 at the maximum tolerated dose (Arm 1), AMG 655 at a lower dose (Arm 2), or AMG 655 placebo (Arm 3) IV Q3W. Randomization will be stratified by ECOG (0 or 1) and disease stage (IIIb or IV/recurrent).

Timeline

Start

2008-01

Primary completion

2011-03

Completion

2011-03

Outcome

Missed primary endpoint

paper Median PFS was 5.4 months (95% confidence interval [CI] 4.1-6.3) in arm 1 (hazard ratio [HR] 0.84 [95% CI 0.57-1.24]; p = 0.41) PMID 23370314 ↗

paper 4.8 months (95% CI 3.2-6.5) in arm 2 (HR 0.93 [0.64-1.35]; p = 0.57), and 5.5 months (95% CI 4.3-5.7) in arm 3. PMID 23370314 ↗

paper Although well tolerated, the addition of conatumumab to PC did not improve outcomes in unselected patients with previously untreated advanced NSCLC. PMID 23370314 ↗

Publications

• Paz-Ares L, Balint B, de Boer RH, van Meerbeeck JP, Wierzbicki R, De Souza P, Galimi F, Haddad V, Sabin T, Hei YJ, Pan Y, Cottrell S, Hsu CP, RamLau R. A randomized phase 2 study of paclitaxel and carboplatin with or without conatumumab for first-line treatment of advanced non-small-cell lung cancer. J Thorac Oncol. 2013 Mar;8(3):329-37. doi: 10.1097/JTO.0b013e31827ce554.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Conatumumab	Monoclonal antibody	3 mg/kg	Intravenous
Subject	Conatumumab	Monoclonal antibody	15 mg/kg	Intravenous

Indications