Abstract 1379P
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.
Editorial acknowledgement
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, Principal Investigator: Gilead Sciences; Financial Interests, Institutional, Principal Investigator: GlaxoSmithKline; Financial Interests, Institutional, Principal Investigator: Gossamer Bio; Financial Interests, Institutional, Principal Investigator: Hoffman-LaRoche; Financial Interests, Institutional, Principal Investigator: Hutchison MediPharma; Financial Interests, Institutional, Principal Investigator: ImmuneOncia Therapeutics; Financial Interests, Institutional, Principal Investigator: Incyte; Financial Interests, Institutional, Principal Investigator: Jounce Therapeutics; Financial Interests, Institutional, Principal Investigator: Mabspace Biosciences; Financial Interests, Institutional, Principal Investigator: MacroGenics, Inc.; Financial Interests, Institutional, Principal Investigator: Medimmune; Financial Interests, Institutional, Principal Investigator: Medivation; Financial Interests, Institutional, Principal Investigator: MERCK; Financial Interests, Institutional, Principal Investigator: Millennium; Financial Interests, Institutional, Principal Investigator: Mirati Therapeutics; Financial Interests, Institutional, Principal Investigator: Novartis Pharmaceuticals; Financial Interests, Institutional, Principal Investigator: Oncologie; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: PsiOxus; Financial Interests, Institutional, Principal Investigator: Puma Biotechnology; Financial Interests, Institutional, Principal Investigator: Regeneron Pharmaceuticals; Financial Interests, Institutional, Principal Investigator: Seattle Genetics; Financial Interests, Institutional, Principal Investigator: Synermore Biologics; Financial Interests, Institutional, Principal Investigator: Taiho Pharmaceutical; Financial Interests, Institutional, Principal Investigator: TopAlliance Biosciences; Financial Interests, Institutional, Principal Investigator: Turning Point Therapeutics; Financial Interests, Institutional, Principal Investigator: Vedanta Biosciences; Financial Interests, Institutional, Principal Investigator: Vertex Pharmaceuticals; Financial Interests, Institutional, Principal Investigator: Xencor Inc. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Genentech/Roche; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Taiho; Financial Interests, Personal, Advisory Board: ASLAN; Financial Interests, Personal, Advisory Board: Halozyme; Financial Interests, Personal, Advisory Board: Zymeworks; Financial Interests, Personal, Advisory Board: BMS/Celgene; Financial Interests, Personal, Advisory Board: BeiGene; Financial Interests, Personal, Advisory Board: Basilea; Financial Interests, Personal, Advisory Board: Turning Point; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Array; Financial Interests, Institutional, Research Grant: Eli Lilly; Financial Interests, Institutional, Research Grant: Servier; Financial Interests, Institutional, Research Grant: BeiGene; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Handok. A. Spira: Financial Interests, Personal, Stocks/Shares: Lilly; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Other, Honoraria: AstraZeneca/MedImmune; Financial Interests, Personal, Other, Honoraria: CytomX Therapeutics; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Advisory Role, Research funding: Amgen; Financial Interests, Institutional, Advisory Role, Research funding: Array BioPharma; Financial Interests, Institutional, Advisory Role, Research funding: AstraZeneca/MedImmune; Financial Interests, Personal, Advisory Role, Research funding: Incyte; Financial Interests, Personal, Advisory Role, Research funding: Novartis; Financial Interests, Institutional, Other, Research funding: AbbVie; Financial Interests, Institutional, Other, Research funding: ADC Therapeutics; Financial Interests, Institutional, Other, Research funding: Amgen; Financial Interests, Institutional, Other, Research funding: Arch Therapeutics; Financial Interests, Institutional, Other, Research funding: Astellas Pharma; Financial Interests, Institutional, Other, Research funding: Astex Pharmaceuticals; Financial Interests, Institutional, Other, Research funding: AstraZeneca; Financial Interests, Institutional, Other, Research funding: Boehringer Ingelheim; Financial Interests, Institutional, Other, Research funding: Bristol-Myers Squibb; Financial Interests, Institutional, Other, Research funding: CytomX Therapeutics; Financial Interests, Institutional, Other, Research funding: Daiichi Sankyo; Financial Interests, Institutional, Other, Research funding: Gritstone Oncology; Financial Interests, Institutional, Other, Research funding: Ignyta; Financial Interests, Institutional, Other, Research funding: Incyte; Financial Interests, Institutional, Other, Research funding: LAM Therapeutics; Financial Interests, Institutional, Other, Research funding: Loxo; Financial Interests, Institutional, Other, Research funding: MacroGenics; Financial Interests, Institutional, Other, Research funding: MedImmune; Financial Interests, Institutional, Other, Research funding: Newlink Genetics; Financial Interests, Institutional, Other, Research funding: Novartis; Financial Interests, Institutional, Other, Research funding: Plexxikon; Financial Interests, Institutional, Other, Research funding: Roche; Financial Interests, Institutional, Other, Research funding: Takeda; Financial Interests, Institutional, Other, Research funding: Trovagene. S. Ulahannan: Financial Interests, Personal, Advisory Board: Array; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Syros; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Institutional, Principal Investigator: AbbVie, Inc.; Financial Interests, Institutional, Principal Investigator: ArQule, Inc.; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Atreca; Financial Interests, Institutional, Principal Investigator: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator: Bristol-Myers Squibb; Financial Interests, Institutional, Principal Investigator: Celgene Corporation; Financial Interests, Institutional, Principal Investigator: Ciclomed LLC; Financial Interests, Institutional, Principal Investigator: Evelo Biosciences, Inc.; Financial Interests, Institutional, Principal Investigator: G1 Therapeutics, Inc.; Financial Interests, Institutional, Principal Investigator: GlaxoSmithKline; Financial Interests, Institutional, Principal Investigator: IGM biosciences; Financial Interests, Institutional, Principal Investigator: Incyte; Financial Interests, Institutional, Principal Investigator: Isofol; Financial Interests, Institutional, Principal Investigator: Klus Pharma, Inc.; Financial Interests, Institutional, Principal Investigator: MacroGenics, Inc.; Financial Interests, Institutional, Principal Investigator: Merck Co. Inc.; Financial Interests, Institutional, Principal Investigator: Mersana Therapeutics; Financial Interests, Institutional, Principal Investigator: OncoMed Pharmaceuticals, Inc.; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Regeneron, Inc.; Financial Interests, Institutional, Principal Investigator: Revolution Medicines, Inc.; Financial Interests, Institutional, Principal Investigator: Synermore Biologics Co; Financial Interests, Institutional, Principal Investigator: Takeda; Financial Interests, Institutional, Principal Investigator: Tarveda Therapeutics; Financial Interests, Institutional, Principal Investigator: Tesaro; Financial Interests, Institutional, Principal Investigator: Tempest; Financial Interests, Institutional, Principal Investigator: Vigeo Therapeutics, Inc. E.J. Avery: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Personal, Other, Travel, accommodations, expenses: AstraZeneca. P.M. Boland: Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Institutional, Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding: Merck; Financial Interests, Institutional, Funding: Bayer; Financial Interests, Institutional, Funding: Boston Biomedical; Financial Interests, Institutional, Funding: Ipsen; Financial Interests, Institutional, Funding: Athenex; Financial Interests, Institutional, Funding: AbbVie. J. Chao: Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Advisory Board: Astellas; Other, Personal, Other, Consulting: AstraZeneca; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Other, Personal, Other, Consulting: Lilly; Financial Interests, Personal, Advisory Board: MacroGenics, Inc.; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Advisory Board: Merck; Other, Personal, Other, Consulting: Ono Pharmaceuticals; Other, Personal, Other, Consulting: Roche; Financial Interests, Personal, Advisory Board: Turning Point Therapeutics; Financial Interests, Personal, Advisory Board: Brooklyn Immunotherapeutics; Financial Interests, Institutional, Funding: Merck. H.C. Chung: Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Merck-Serono; Financial Interests, Institutional, Research Grant: BMS/Ono; Financial Interests, Institutional, Research Grant: Taiho; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Beigene; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Zymework; Financial Interests, Personal, Other, Honoraria: Merck-Serono; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Advisory Role: Taiho; Financial Interests, Personal, Advisory Role: Celltrion; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Merck-Serono; Financial Interests, Personal, Advisory Role: Gloria; Financial Interests, Personal, Advisory Role: Beigene; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Zymework. F. Gardner: Financial Interests, Personal, Advisory Role: Oasis 360; Financial Interests, Personal, Advisory Role: bioTheranostics; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Leadership Role: Florida Cancer Specialists; Financial Interests, Personal, Speaker’s Bureau: Epizyme; Financial Interests, Personal, Speaker’s Bureau: Regeneron; Financial Interests, Personal, Speaker’s Bureau: Sanofi; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Institutional, Funding: Novartis Pharmaceuticals UK Ltd; Financial Interests, Institutional, Funding: Genentech; Financial Interests, Institutional, Funding: Lilly; Financial Interests, Institutional, Funding: Astellas Pharma; Financial Interests, Institutional, Funding: MacroGenics; Financial Interests, Institutional, Funding: Pharmacyclics. S.J. Klempner: Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Merck; Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Astellas; Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, One time advisory board: Natera; Financial Interests, Personal, Advisory Board, Stomach Cancer Advisory Board: Pieris; Financial Interests, Personal, Stocks/Shares: Turning Point Therapeutics; Non-Financial Interests, Personal, Principal Investigator: Leap Therapeutics; Financial Interests, Personal and Institutional, Principal Investigator: Astellas; Financial Interests, Personal and Institutional, Advisory Board, MacroGenics, Inc.: Astellas; Non-Financial Interests, Institutional, Principal Investigator: MacroGenics, Inc. K. Lee: Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: ISU ABXIS; Financial Interests, Institutional, Principal Investigator: ABLBIO; Financial Interests, Institutional, Principal Investigator: ALX Oncology; Financial Interests, Institutional, Principal Investigator: AstraZeneca; Financial Interests, Institutional, Principal Investigator: Beigene; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Five Prime Therapeutics; Financial Interests, Institutional, Principal Investigator: Genexine; Financial Interests, Institutional, Principal Investigator: Green Cross Corp.; Financial Interests, Institutional, Principal Investigator: LSK BioPharma; Financial Interests, Institutional, Principal Investigator: MacroGenics, Inc.; Financial Interests, Institutional, Principal Investigator: Merck KGaA; Financial Interests, Institutional, Principal Investigator: Merck Sharp & Dohme; Financial Interests, Institutional, Principal Investigator: Oncologie; Financial Interests, Institutional, Principal Investigator: Ono pharmaceutical; Financial Interests, Institutional, Principal Investigator: Pfizer; Financial Interests, Institutional, Principal Investigator: Pharmacyclics; Financial Interests, Institutional, Principal Investigator: Taiho Pharmaceutical; Financial Interests, Institutional, Principal Investigator: Y-BIOLOGICS; Financial Interests, Institutional, Principal Investigator: Zymeworks. J. Peguero: Financial Interests, Personal, Full or part-time Employment: Oncology Consultants; Financial Interests, Personal, Leadership Role: Oncology Consultants; Financial Interests, Personal, Stocks/Shares: Oncology Consultants; Financial Interests, Personal, Stocks/Shares: Zogen; Financial Interests, Personal, Other, Honoraria: Tempus; Financial Interests, Personal, Invited Speaker, Honoraria: Agendia; Financial Interests, Personal, Invited Speaker, Honoraria: Guardant Health; Financial Interests, Personal, Advisory Role: TerSera Therapeutics; Financial Interests, Personal, Speaker’s Bureau: Tempus; Financial Interests, Personal, Speaker’s Bureau: Agendia; Financial Interests, Personal, Speaker’s Bureau: Guardant Health; Financial Interests, Institutional, Principal Investigator: Immutep; Financial Interests, Institutional, Principal Investigator: GNE/Roche; Financial Interests, Institutional, Principal Investigator: Immatics; Financial Interests, Institutional, Principal Investigator: NovoCure; Financial Interests, Institutional, Principal Investigator: Amgen; Financial Interests, Institutional, Principal Investigator: EMD Serono; Financial Interests, Institutional, Principal Investigator: Loxo Oncology; Financial Interests, Institutional, Principal Investigator: Eli Lilly; Financial Interests, Institutional, Principal Investigator: Turning Point Therapeutics; Financial Interests, Institutional, Principal Investigator: Barvarian Nordic; Financial Interests, Institutional, Principal Investigator: IncMed; Financial Interests, Institutional, Principal Investigator: Immunity Bio (Altor); Financial Interests, Institutional, Principal Investigator: Incyte; Financial Interests, Institutional, Principal Investigator: AbbVie; Financial Interests, Institutional, Principal Investigator: MacroGenics; Financial Interests, Institutional, Principal Investigator: Dizal; Financial Interests, Institutional, Principal Investigator: BerGenBio; Financial Interests, Institutional, Principal Investigator: Epizyme; Financial Interests, Institutional, Principal Investigator: Astella; Financial Interests, Institutional, Principal Investigator: Janssen; Financial Interests, Institutional, Principal Investigator: Thrive Earlier Detection Corp; Financial Interests, Institutional, Principal Investigator: Boehringer Ingelheim; Financial Interests, Institutional, Principal Investigator: TerSera; Financial Interests, Institutional, Principal Investigator: Natera; Financial Interests, Institutional, Principal Investigator: Ipsen Bioscience; Financial Interests, Institutional, Principal Investigator: Mitati Therapeutics; Financial Interests, Institutional, Principal Investigator: Calithera Biosciences; Financial Interests, Institutional, Principal Investigator: Effector Therapeutics, Inc.; Financial Interests, Institutional, Principal Investigator: KeChow Pharmaceuticals, Inc.; Financial Interests, Institutional, Principal Investigator: Sermonix Pharmaceuticals; Financial Interests, Personal, Other, Travel/accomodations/expenses: Tempus; Financial Interests, Personal, Other, Travel/accomodations/expenses: Agendia; Financial Interests, Personal, Other, Travel/accomodations/expenses: Guardant Health. J. Sun: Financial Interests, Personal, Full or part-time Employment: MacroGenics, Inc.; Financial Interests, Personal, Stocks/Shares: MacroGenics, Inc. M.K. Rosales: Financial Interests, Personal, Full or part-time Employment: MacroGenics, Inc.; Financial Interests, Personal, Full or part-time Employment: MacroGenics, Inc. Y. Kang: Financial Interests, Personal, Advisory Role: ALX Oncology; Financial Interests, Personal, Advisory Role: Zymeworks; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: MacroGenics, Inc.; Financial Interests, Personal, Advisory Role: Daehwa; Financial Interests, Personal, Advisory Role: Blueprint; Financial Interests, Personal, Advisory Role: Surface Oncology; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: Merck MSD. All other authors have declared no conflicts of interest.