2019 GI Cancers Symposium: Addition of Andecaliximab to mFOLFOX6 in Treatment-Naive Advanced Gastric or GEJ Adenocarcinoma
A phase I/Ib study found that the addition of andecaliximab, a monoclonal antibody that inhibits matrix metalloproteinase 9, to modified fluorouracil (5-FU), leucovorin, and oxaliplatin (mFOLFOX6) showed activity in gastric and or gastroesophageal junction (GEJ) carcinoma. Based on these results, the phase III GAMMA-1 trial was initiated to investigate the efficacy and safety of MFOLFOX6 with or without andecaliximab in patients with treatment-naive, HER2-negative gastric or GEJ adenocarcinoma. Results of GAMMA-1 were presented by Shah et al at the 2019 Gastrointestinal Cancers Symposium (Abstract 4).
GAMMA-1 Methods
Between September 2015 and May 2017, 432 patients were randomly assigned to treatment with either mFOLFOX6 plus andecaliximab (n = 218) or mFOLFOX6 plus placebo (n = 214). Oxaliplatin was administered on days 1 and 15 of each 28-day treatment cycle (total of 6 cycles), followed by leucovorin and 5-FU dosing on days 1 and 15 of each 28-day treatment cycle until disease progression. Andecaliximab or placebo 800 mg was infused on days 1 and 15 of each 28-day cycle until disease progression.
The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), overall response rate (ORR) as defined by RECIST 1.1, and safety.
Findings
Median OS was 12.5 vs 11.8 months in the andecaliximab vs placebo treatment groups, respectively (hazard ratio [HR] = 0.93, two-sided P = .56). Median PFS was 7.5 months in the andecaliximab group vs 7.1 months in the placebo group (HR = 0.94, two-sided P = .10). Median investigator-assessed ORR was 50.5% in patients treated with andecaliximab and 41.1% in patients treated with placebo (two-sided P = .049).
Nausea, diarrhea, neutropenia, and fatigue were cited as the most common treatment-emergent adverse events present in the study, and there were no meaningful differences in the safety profile of the groups treated with andecaliximab or placebo.
The study authors concluded, “Addition of andecaliximab to mFOLFOX6 does not improve overall survival in patients with untreated HER2-negative gastric or GEJ adenocarcinoma.”
Disclosure: The study authors’ full disclosures can be found at coi.asco.org.
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