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RESEARCH PRODUCT

The GAIN-C study (BP25438): Randomized phase II trial of RG7160 (GA201) plus FOLFIRI, compared to cetuximab plus FOLFIRI or FOLFIRI alone in second-line KRAS wild type (WT) or mutant metastatic colorectal cancer (mCRC).

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TPS3637 Background: GA201 is a novel, dual-acting, humanized, glycoengineered IgG1 anti-EGFR monoclonal antibody, with enhanced antibody-dependent cellular cytotoxicity (ADCC) activity in combination with signal inhibition. GA201 demonstrates significantly enhanced in vitro/vivo activity compared to cetuximab (cet) both as a single agent and in combination with irinotecan, in both KRAS mutant and BRAF mutant models and promising clinical activity in ph I and neo-adjuvant trials (Paz Ares et al, JCO 2011) including KRAS mutant mCRC. A randomized ph II program was launched: one study in NSCLC and GAIN-C in mCRC (NCT01326000), which is presented here. Methods: Main inclusion criteria are progression on 1L containing oxaliplatin, ECOG 0-1, and adequate hematological and liver function. Main exclusion criteria: prior anti-EGFR treatment. A total of 160 patients in 2L mCRC (stratified for EGFR expression, disease progression before or after 6 months after starting 1L, prior treatment with bevacizumab Y vs N) will be randomized to receive either GA201 (day 1, 8 of cycle 1 then q2W) or cet (qW) + FOLFIRI q2W (KRAS WT) or to receive GA201+ FOLFIRI or FOLFIRI alone (KRAS mutant). Collection of archival tumor plus a mandatory fresh tumor biopsy at baseline were implemented because ph I data showed that EGFR expression is not concordant between the two specimen types and to optimize assessment of potential immune related biomarkers. The fresh tumor biopsy will be centrally analyzed for EGFR (immunohistochemistry) and KRAS status. Primary objective is progression free survival; secondary endpoints are to define objective response rates, the safety profile, pharmacokinetics and pharmacodynamics. A comprehensive biomarker program (blood and tumor), mainly immune-phenotyping, immunohistochemistry in tumor samples (Ventana) and immune functional tests (including adaptive responses) were set up to investigate potential predictive biomarkers and the mode of action of GA201. Study is ongoing worldwide in 9 countries with the safety run-in phase completed in Nov 2011. Recruitment is planned to be completed by end of April 2012.