Margetuximab (M) with retifanlimab (R) in HER2+, PD-L1+1st-line unresectable/metastatic gastroesophageal adenocarcinoma (GEA): MAHOGANY cohort A

초록

Background The monoclonal antibody (mAb) trastuzumab plus chemotherapy has been 1st-line standard of care in HER2+ metastatic GEA for a decade. M is an investigational (in GEA) anti-HER2 mAb engineered to confer enhanced Fc dependent antitumor activity across all Fc region gamma receptor genotypes. M may potentiate innate immunity (i.e. antibody-dependent cellular cytotoxicity) and adaptive immunity (i.e. anti-HER2–directed T-cell responsiveness). R, an investigational humanized IgG4 mAb, binds to PD-1 and blocks its interaction with PD-L1/2. Methods MAHOGANY is a 2-cohort study in unresectable metastatic/locally advanced GEA. Cohort A (100 pt single arm) will determine safety/efficacy of Q3W M 15 mg/kg plus R 375 mg in HER2 3+, PD-L1+ (CPS ≥1) and non–microsatellite instability high pts. Primary endpoint of Cohort A is centrally-reviewed overall response rate (ORR); Investigator-assessed ORR is supportive. Results As of 16 April 2021, 43 pts were enrolled, with median exposure of 4.2 months and median duration of follow-up of 4.6 months. Safety data are available on 43; efficacy data are available on 43 with baseline scan for response assessment by the investigators. Of these 43, 37 have reached first tumor reassessment, with 1 confirmed complete response, 11 confirmed partial responses, 1 unconfirmed complete response, 11 unconfirmed partial responses, 7 stable disease, and 6 progressive disease (5 PD at first scan, 1 clinical PD). Tumor shrinkage was seen in 30/35 pts (85.7%) with at least 1 post-baseline target lesion measurement. The most common treatment-related adverse events were infusion related reaction (8/43, 18.6%), diarrhea and fatigue (6/43, 14% each). Grade 3 treatment-related events were singularly reported with no ≥ Grade 3 infusion related reaction or diarrhea. Regarding immune-related events, 1 pt discontinued due to renal dysfunction possibly related to M+R, 4 had hypothyroidism and 1 had immune-related renal dysfunction. Conclusions This first report of MAHOGANY Cohort A of M plus R suggests the combination is well tolerated. The updated efficacy data including centrally-reviewed scans will be available at presentation. Clinical trial identification NCT04082364. Legal entity responsible for the study MacroGenics, Inc. Funding MacroGenics, Inc. Disclosure D.V. Catenacci: Financial Interests, Personal, Other, Honoraria: Amgen; Astellas Pharma; Bristol-Myers Squibb; Five Prime Therapeutics; Foundation Medicine; Genentech/Roche; Gritsone Oncology; Guardant Health; Lilly; Merck; Seattle Genetics; Taiho Pharmaceutical; Tempus; Daichii Sankyo; Basilea; QED; Arcus; Ono; Archer; Natera; Financial Interests, Personal, Advisory Role: Amgen; Astellas Pharma; Bristol-Myers Squibb; Genentech/Roche; Lilly; Merck; Seattle Genetics; Taiho Pharmaceutical; Daichii Sankyo; Ono; Arcus; Basilea; QED; Archer; Natera; Financial Interests, Personal, Speaker’s Bureau: Foundation Medicine; Genentech/Roche; Guardant Health; Lilly; Merck; Daichii Sankyo; Tempus. H. Park: Financial Interests, Institutional, Principal Investigator: Ambrx; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: Aprea; Financial Interests, Institutional, Principal Investigator: Array; Financial Interests, Institutional, Principal Investigator: Bayer; Financial Interests, Institutional, Principal Investigator: BeiGene; Financial Interests, Institutional, Principal Investigator: BJ Bioscience; Financial Interests, Institutional, Principal Investigator: Bristol-Myers Squibb; Financial Interests, Institutional, Principal Investigator: Daiichi Pharmaceutical; Financial Interests, Institutional, Principal Investigator: Eli Lilly; Financial Interests, Institutional, Principal Investigator: Elicio Therapeutics; Financial Interests, Institutional, Principal Investigator: EMD Serono; Financial Interests, Institutional, Principal Investigator: Genentech; Financial Interests, Institutional,