A randomized, phase Ib/II trial of rilotumumab (AMG 102; ril) or ganitumab (AMG 479; gan) with panitumumab (pmab) versus pmab alone in patients (pts) with wild-type (WT) <i>KRAS</i> metastatic colorectal cancer (mCRC): Primary and biomarker analyses.

Abstract

3500 Background: Pmab, ril, and gan are fully human monoclonal antibodies against epidermal growth factor receptor, hepatocyte growth factor, and insulin-like growth factor receptor 1, respectively. This 3-part study examined the safety and efficacy of ril or gan with pmab in pts with mCRC expressing WT KRAS. Methods: Part 2 was a phase II, randomized, double-blinded, placebo-controlled trial of pmab (6 mg/kg) + placebo (Arm 1) vs pmab + ril (10 mg/kg, Arm 2) vs pmab + gan (12 mg/kg, Arm 3), all administered Q2W until disease progression or intolerance. Pts were ≥ 18 yrs old, had ECOG PS 0/1, and prior irinotecan and/or oxaliplatin. The primary endpoint for Part 2 was objective response rate (ORR). A Bayesian approach was undertaken to determine a meaningful improvement in ORR in the combination arms. Secondary endpoints included progression-free survival (PFS) and safety (adverse events [AEs]). Biomarker analyses including c-Met expression by immunohistochemistry (IHC) on archival tumor samples were completed. Correlation of c-Met expression with outcomes for the pmab + ril combination is ongoing. Results: 142 pts were enrolled; 58% were men; mean age was 59.7 yrs; 40%/59% had ECOG PS of 0/1, respectively. ORRs are shown (table). Median PFS (95% CI) was 3.7 (2.5-5.3), 5.2 (3.6-5.4), and 5.3 (2.7-5.7) months for Arms 1, 2, and 3, respectively. Grade ≥ 3 AEs were reported in 54%, 79%, and 72% of pts in Arms 1, 2, and 3, respectively and commonly included rash, dermatitis, and hypomagnesemia. c-Met IHC results were obtained for 134 of the142 pts (94%). Conclusions: Pmab + ril met the prespecified criterion for improvement in ORR (greater than Arm 1). Pmab in combination with ril or gan was well tolerated. Results of biomarker analyses of pmab/ril including c-Met staining will be presented. Arm 1 Arm 2 Arm 3 Best response, n (%) Pmab +placebo N = 48 Pmab +ril N = 48 Pmab +gan N = 46 Partial response 10 (21) 15 (31) 10 (22) Stable disease 17 (35) 19 (40) 18 (39) Progressive disease 16 (33) 11 (23) 15 (33) Unevaluable/not done 5 (10) 3 (6) 3 (6) Posterior probability of OR>1* 0.93 0.63 *Odds ratio relative to Arm 1 for ORR.