Manish A. Shah, MD from Weill Cornell Medicine and New York-Presbyterian discuss the ASCO Pubs – Phase III Study to Evaluate Efficacy and Safety of Andecaliximab With mFOLFOX6 as First-Line Treatment in Patients With Advanced Gastric or GEJ Adenocarcinoma (GAMMA-1).
Link to Report –
https://ascopubs.org/doi/full/10.1200/JCO.20.02755
Synopsis:
PURPOSE: Andecaliximab (ADX) is a monoclonal antibody that inhibits matrix metalloproteinase 9, an extracellular enzyme that plays a role in tumor development, metastasis, and matrix remodeling. In patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma, a phase I and Ib analysis of modified oxaliplatin, leucovorin, and fluorouracil (mFOLFOX6) with ADX showed promising antitumor activity.
MATERIALS AND METHODS: The efficacy and safety of mFOLFOX6 with and without ADX in patients with untreated human epidermal growth factor receptor 2–negative gastric or GEJ adenocarcinoma were investigated in this phase III, randomized, double-blinded, placebo (PBO)-controlled multicenter review. The participants were randomly assigned to either mFOLFOX6 + ADX or mFOLFOX6 + PBO. On days 1 and 15 of each 28-day period, ADX/PBO 800 mg was infused. The protocol was followed before the illness progressed or intolerance developed. Overall survival (OS) was the primary outcome, with progression-free survival (PFS), objective response rate (RECIST 1.1), and protection as secondary outcomes.
RESULTS: From September 2015 to May 2017, 432 patients were randomly assigned to ADX or PBO, with 218 receiving ADX and 214 receiving PBO. In the ADX and PBO classes, the median OS was 12.5 months versus 11.8 months, respectively. In the ADX and PBO classes, the median PFS was 7.5 months versus 7.1 months, respectively. The ADX group had a 51% objective response rate, while the PBO group had a 41% objective response rate. Patients under 65 years old had a better OS and PFS with ADX than PBO in subgroup analyses; the P values and CIs were not balanced for multiplicity. There were no significant variations in the ADX and PBO groups’ safety profiles.
CONCLUSION: In unselected patients with untreated human epidermal growth factor receptor 2–negative gastric or GEJ adenocarcinoma, adding ADX to mFOLFOX6 did not enhance OS.