Phase II study of PRO95780 plus paclitaxel, carboplatin, and bevacizumab (PCB) in non-small cell lung cancer (NSCLC).

Abstract

7535 Background: Treatment effect of PRO95780—a fully human affinity-matured IgG1 monoclonal antibody that induces DR5- mediated apoptosis in diverse cancer cell lines and xenograft models—was assessed in combination with PCB in previously untreated patients (pts) with advanced NSCLC. Methods: In this randomized, double-blind, placebo-controlled phase II trial, pts received PCB + PRO95780 (n=62) or PCB + placebo (n=62) for up to six 21-day cycles, then B + PRO95780/placebo for up to 28 more cycles. Adverse event (AE) and laboratory data were monitored. The primary efficacy measure was progression-free survival (PFS) as assessed by blinded, independent review. An exploratory objective was to evaluate prespecified biomarkers that might predict benefit from PRO95780. Results: Pts in the PRO95780 arm (median PRO95780 exposure = 6 cycles) had higher rates of grade 3-5 AEs (87%, vs. 68% for placebo), including higher rates of neutropenia, elevated ALT/AST, and supraventricular tachycardia. Efficacy data (with 95% confidence intervals) are shown below; none of the differences was statistically significant. Pts homozygous for a specific polymorphism of the Fcγ type IIa receptor that codes for a histidine residue at amino acid 131 showed a trend toward better PFS (HR=0.49; 95% CI=0.17-1.45) and objective response rate (odds ratio=2; 95% CI=0.38-10.58). Conclusions: Adding PRO95780 to PCB appeared to increase the rate of some AEs but did not appear to improve efficacy outcomes in unselected pts with advanced NSCLC. A possible trend for better outcomes among pts with H/H Fcγ receptor IIa genotype was seen. Placebo + PCB PRO95780 + PCB Median PFS, mo 7.0 (5.6-9.7) 7.9 (5.4-9.6) HR 1.06 (0.6-1.8) Median overall survival, mo 12.6 (9.8-16.8) 9.9 (8.3-15.8) HR 1.18 (0.71-1.98) Objective response rate*, % 42 (30-55) 40 (29-54) Abbreviation: HR, hazard ratio. * All partial responses. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Genentech Roche