LBA73 - Pathological complete response (pCR) to durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) in resectable gastric and gastroesophageal junction cancer (GC/GEJC): Interim results of the global, phase III MATTERHORN study

Background

The global, Phase 3, randomised, double-blind, placebo (P)-controlled MATTERHORN study (NCT04592913) assesses perioperative durvalumab (D) with FLOT in participants (pts) with resectable GC/GEJC. Results of a pre-planned interim analysis (IA) are reported.

Methods

Pts with resectable (>T2 N0-3 M0/T0-4 N1-3 M0) GC/GEJC were randomised 1:1 to D 1500 mg or P every 4 weeks (Q4W) on Day 1 plus FLOT Q2W on Days 1 and 15 for 4 cycles (2 doses of D or P and 4 doses of FLOT pre- and post-operative), followed by D 1500 mg or P on Day 1 Q4W for 10 further cycles. IA was conducted after all randomised pts underwent or were precluded from surgery. Superiority of pCR rate (α=0.1% [2-sided]) by central review (Modified Ryan) was assessed. Surgical and safety outcomes were also assessed.

Results

There were 474 pts randomised to each treatment arm. Baseline characteristics were balanced between arms; 19% of pts in each enrolled in Asia. The majority of pts had GC (68%), cT3 (66%; cT4, 25%) and cLN+ (70%). A statistically significant improvement in pCR was observed with addition of D to FLOT versus P (19% vs 7%; Δ12%; odds ratio [OR], 3.08; p<0.00001; Table). Combined pCR/near-complete pathological response (pnCR) rate was 27% with D vs 14% with P. Surgery rate and R0 resection rate (in pts who underwent surgery) were similar with D (87% and 86%, respectively) vs P (84% and 86%, respectively). Downstaging favoured D vs P (pT0, 21% vs 10%; pN0, 47% vs 33%; by central review). Median D and P exposure was similar. Adverse event rates were similar between arms (Table). Table: LBA73

*In pts with surgery: D + FLOT, n=430, P + FLOT, n=422. †In safety analysis set: D + FLOT, n=475, P + FLOT, n=469. TRAE, treatment-related AE.

Conclusions

The addition of D to perioperative FLOT therapy demonstrated a clinically meaningful and statistically significant improvement in pCR in resectable GC/GEJC, with a tolerable safety profile. The MATTERHORN study is ongoing for the primary endpoint of event-free survival.

Clinical trial identification

NCT04592913.

Editorial acknowledgement

The authors thank the study participants, their families, caregivers and study personnel. Medical writing support, under the direction of the authors, was provided by Andrew Briggs, MA, CMC Connect, a division of IPG Health Medical Communications, in accordance with Good Publication Practice (GPP 2022) guidelines.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

Y.Y. Janjigian: Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb, Merck Serono; Financial Interests, Personal, Advisory Board: RGENIX, Eli Lilly, Daiichi Sankyo, Pfizer, Bayer, Imugene, Merck, Zymeworks Inc., Seagen, Basilea Pharmaceutica, AstraZeneca; Financial Interests, Personal, Other, Consulting: Michael J. Hennessy Associates, Paradigm Medical Communications, Amerisource Bergen, Arcus Biosciences, Geneos Therapeutics, GSK, Imedex, Lynx Health, Mersana Therapeutics, PeerView Institue, Reasearch to Practice, Silverback Therapeutics; Financial Interests, Personal, Stocks/Shares: RGENIX; Financial Interests, Personal and Institutional, Research Grant: NCI, Department of Defense, Cycle for Survival, Fred's Team, RGENIX, Bayer, Genetech/Roche, Bristol-Myers Squibb, Eli Lilly, Merck. S. Al-Batran: Financial Interests, Personal, Advisory Board: Lilly, Bristol-Myers Squibb, MacroGenics, Immutep, MSD Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb, Lilly, AIO Studien gGmbH, MCI Deutschland GmbH; Financial Interests, Personal, Other, CEO/founder: Institute of Clinical Cancer Research IKF at Northwest Hospital; Financial Interests, Institutional, Research Grant: Sanofi, Roche, Celgene, Vifor, Medac, Hospira, Lilly, Eurozyto, Immutep, Ipsen, Bristol-Myers Squibb, MSD Sharp & Dohme, AstraZeneca, German Cancer Aid (Krebshilfe), German Research Foundation, Federal Ministry of Education and Research. Z.A. Wainberg: Financial Interests, Personal, Advisory Board, Honoraria: Amgen, Arcus, AstraZeneca, Daiichi, Bayer, BMS, Merck, Ipsen, Five Prime, Gilead, Arcus, Astellas; Financial Interests, Institutional, Advisory Board, Advisory/Consultancy: Amgen, Arcus, AstraZeneca, Daiichi, Bayer, BMS, Merck, Ipsen, Five Prime, Gilead, Arcus, Astellas; Financial Interests, Personal and Institutional, Research Funding: Amgen, AstraZeneca, Daiichi, Bayer, BMS, Merck, Ipsen, Five Prime, Gilead, Arcus, Astellas, Molecular Templates, Roche/Genentech, Array/Pfizer. E. Van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, ALX, Amgen, Array, Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, Zymeworks; Financial Interests, Institutional, Research Grant: Amgen, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. D. Molena: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca, Johnson & Johnson, Boston Scientific, BMS. K. Muro: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Ono, Chugai; Financial Interests, Personal, Invited Speaker: Eli Lilly, Ono, Daiichi Sankyo, Taiho, Bristol-Myers Squibb, Takeda, Chugai, AstraZeneca, Amgen; Financial Interests, Institutional, Research Grant, Including local PI as role: Astellas, Amgen, Sanofi, Daiichi Sankyo, Taiho, MSD, Pfizer, Merck Biopharma, Eisai, Ono, Novartis; Non-Financial Interests, Principal Investigator: Takeda. L.S. Wyrwicz: Financial Interests, Personal, Advisory Board: BMS, Servier; Financial Interests, Personal and Institutional, Local PI: BMS, MSD, Servier, BeiGene, Roche, AstraZeneca; Financial Interests, Personal, Steering Committee Member: AstraZeneca. D. Oh: Financial Interests, Personal, Advisory Board: AstraZeneca, Novartis, Genentech/Roche, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks, BMS/Celgene, BeiGene, Basilea, Turning Point, Yuhan, Arcus Biosciences, IQVIA, MSD; Financial Interests, Institutional, Research Grant: AstraZeneca, Novartis, Array, Eli Lilly, Servier, BeiGene, MSD, Handok. M. Moehler: Financial Interests, Personal, Advisory Board: BMS, Servier, Amgen, Lilly, BeiGene, Novartis, Taiho, Daiichi, MD, Amgen; Financial Interests, Personal, Invited Speaker: MSD, BMS, Falk foundation, AIO, BeiGene, Amgen; Financial Interests, Institutional, Advisory Board: Bayer, Sanofi; Financial Interests, Personal, Other, Chair: EORTC. M. Garrido: Financial Interests, Personal, Invited Speaker: BMS, novartis, bayer, Pfizer, Merck, Lilly, GBT Biotoscana; Financial Interests, Personal, Advisory Board: MSD, Pfizer, Macrogenic; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Research Grant: BMS, Novartis. J.F. Kurland: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. I. Xynos: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. H. Mann: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Tabernero: Financial Interests, Personal, Advisory Board, scientific consultancy role: Orion Biotechnology, Array Biopharma, AstraZeneca, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics, TheraMyc, Hutchinson MediPharma International, Scandion Oncology, Ona Therapeutics, Sotio Biotech, Inspirna Inc, Scorpion Therapeutics, Tolremo Therapeutics; Financial Interests, Personal, Invited Speaker, educational collaboration: Medscape Education, Physicians Education Resource (PER), PeerView Institute for Medical Education, Imedex / HMP; Financial Interests, Personal, Invited Speaker, educacional collaboration: MJH Life Sciences; Financial Interests, Personal, Advisory Board: Cardiff Oncology; Financial Interests, Personal, Stocks/Shares: Oniria Therapeuics; Financial Interests, Institutional, Research Grant, ACRCelerate: Colorectal Cancer Stratified: Fundación Científica de la Asociación Española Contra el Cáncer; Financial Interests, Institutional, Research Grant, OPTIMISTICC: Opportunity to Investigate the Microbiome’s Impact on Science and Treatment In Colorectal Cancer: Cancer Research UK; Financial Interests, Institutional, Funding, Clinical Trials & Research: Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb International Corporation, Celgene International SARL, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, Janssen-Cilag International NV, Merck Health KGAA, Merck, Sharp & Dohme de España, SA, Novartis Farmacéutica SA, PharmaMar SA, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA, Inc, BeiGene, Boehringer Ingelheim, HalioDX SAS, Hutchinson Medipharma, MedImmune, Menarini, Merus N V, Pfizer, Mirati; Non-Financial Interests, Member of Board of Directors, Board of Directors: Cancer Core Europe, Spanish Association Against Cancer -AECC; Non-Financial Interests, Member of Board of Directors, General Assembly: Horizon Europe Cancer Mission; Non-Financial Interests, Leadership Role, External Scientific Committee: Institute for Health Research INCLIVA – Clinical Hospital of Valencia, IdiSNA –Universidad de Navarra; Non-Financial Interests, Leadership Role, Scientific Advisory Board: Spanish National Cancer Research Centre (CNIO); Non-Financial Interests, Advisory Role, International Scientific Evaluation Committee: Bosch Health Campus (BHC); Non-Financial Interests, Advisory Role, Review Board: National Decade Against Cancer (NCT) - German Consortium for Translational Cancer Research (DKTK); Non-Financial Interests, Advisory Role, Scientific Advisory Board: Karolinska Comprehensive Cancer Centre; Non-Financial Interests, Advisory Role, International Review Committee (IRC): Oncode Institute; Non-Financial Interests, Advisory Role, Scientific Advisory Board (SAB): Oslo University Hospital Comprehensive Cancer Centre (OUH CCC); Non-Financial Interests, Principal Investigator, Clinical Trials & Research: AstraZeneca Pharmaceutics LP, Array Biopharma Inc., BeiGene, Boehringer Ingelheim, Debiopharm International SA, Bristol-Myers Squibb International Corporation, Celgene International SARL, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Menarini, Janssen-Cilag International NV, MedImmune, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Sanofi-Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc; Non-Financial Interests, Leadership Role, Governance Advisory Committee: European Organization for Research and Treatment of Cancer -EORTC; Non-Financial Interests, Leadership Role, Vice Chairman: World Innovative Networking (WIN) Consortium in Personalized Cancer Medicine; Non-Financial Interests, Other, Coordinating PI & Steering Committee Member. Clinical Trials & Research: Array Biopharma Inc., AstraZeneca Pharmaceutical LP, Boehringer Ingelheim, MedImmune, Menarini, Merck Healthcare KGAA, Merck, Sharp & Dohme de España SA, Pfizer, Servier; Non-Financial Interests, Other, Steering Committee Member. Clinical Trials & Research: Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc., HalioDX SAS, Hutchinson Medipharma, Janssen-Cilag International NV, Merus NV, Taiho Pharma USA Inc; Non-Financial Interests, Other, Coordinating PI. Clinical Trials & Research: Mirati; Non-Financial Interests, Member: AACR, ASCO, EACR, EORTC, SEOM; Other, President: Oncology Master Plan – Catalonia Department of Health; Other, Advisory Committee: Advisory Committee on Pharmaceutical Provision Financing under the Spanish National Health System. All other authors have declared no conflicts of interest.