1062P - Anti-PD1 efficacy in European patients with advanced MSI-H/MMRd non-colorectal cancers

Background

Anti-PD1 immunotherapy is approved by the US FDA since 2017 for the treatment of adult & pediatric unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (MMRd) advanced solid tumours. In Europe, the EMA has approved anti-PD1 immunotherapy for MSI-H/MMRd cancers in 2022 for only 5 tumour indications, including colorectal cancers (CRC). Here we report the results of nivolumab, an anti-PD1 immunotherapy, in European non-CRC MSI-H/MMRd cancer patients.

Methods

AcSé nivolumab is a multi-centre, single arm, phase II basket trial launched by the French National Cancer Institute (INCa) and sponsored by Unicancer, testing the anti-PD-1 nivolumab in rare advanced and unapproved tumour indications. Here we report the results of the MSI-H/MMRd cohort. Nivolumab was administered at 240 mg IV q2w until disease progression or toxicity for a maximum of 2 years. The primary endpoint was the RECIST 1.1 objective response rate (ORR) at 12 weeks. Updated results with a mean follow-up of 21 months and a specific focus on non-EMA (European Medicines Agency) approved indications are reported.

Results

From July 2017 to October 2018, 50 patients (mean age 63 years) were enrolled. Primary locations were endometrial (19), gastric (10), small bowel (6), biliary (4), Genito-Urinary (GU) (3), breast (2), pancreas (5), and anal (1). 94% of patients were previously treated and 42% had ≥2 previous lines. The mean number of 2 weeks cycles was 28/patient. The ORR at 12 weeks was 34% (95%CI, 21.2 to 48.8) with a best overall ORR of 50% (95%CI, 35.5 to 64.5) and a median time to response of 5.5 months. Median progression-free survival was 29.7 months (95%CI, 4.6 to NA). Among the 17 responders at 12-weeks, 12 (70%) were still responding after 24 months of treatment. 6-month overall survival rate was 77.9% (95%CI, 67.1 to 90.3%). Among the 11 patients with rare MSI primary cancer (pancreas, breast, anal, GU), the overall ORR was 36% (4 patients). No new safety signals has been observed.

Conclusions

This study confirms the anti-PD1 nivolumab efficacy in non-colorectal MSI patients, even in rare MSI tumours of European patients. A MSI-H/MMRd tumour agnostic approval of anti-PD1 immunotherapy should be considered by the EMA.

Clinical trial identification

NCT03012581 EudraCT 2016-002257-37.

Editorial acknowledgement

Legal entity responsible for the study

Unicancer.

Funding

La Ligue Nationale contre le Cancer, The French National Cancer Institute (INCa) and BMS.

Disclosure

C. Tournigand: Non-Financial Interests, Leadership Role: GERCOR; Non-Financial Interests, Advisory Role: Fondation APHP. S. Oudard: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Financially compensated role, Honoraria: AZ, Astellas, Bayer, BMS, Janssen, Merck, MSD, Novartis, Pfizer, Sanofi, IPSEN; Financial Interests, Personal, Financially compensated role, Travel Accommodations/Expenses: EISAI, Roche. E.B. Saada: Financial Interests, Personal, Project Lead: AstraZeneca, Merck Serono. D. Pouessel: Financial Interests, Personal, Invited Speaker: Ipsen, Bristol-Myers-Squibb, AstraZeneca, Astellas Pharma, MSD Oncology, Pfizer / Astellas; Financial Interests, Personal, Advisory Board: Astellas Pharma, Pfizer, MSD Oncology, Bristol-Myers-Squibb, Merck; Financial Interests, Institutional, Local PI: Merck Sharp & Dohme, Roche, Bristol-Myers-Squibb, AstraZeneca, Seagen. C. Le Tourneau: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck Serono, Nanobiotix, Roche, Rakuten, Seattle Genetics, GSK, Celgene, ALX Oncology, Exscientia. P. Augereau: Financial Interests, Personal, Financially compensated role, Honoraria: GSK, AZD DAICHI, PFIZER, NOVARTIS. J. Soria: Financial Interests, Personal, Full or part-time Employment, From Sept 2017 to Dec 2019: AstraZeneca; Financial Interests, Personal, Member of Board of Directors, 2019-2021: Hookipa Pharmaceuticals; Financial Interests, Personal, Full or part-time Employment, SVP Amgen since August 2021: Amgen; Financial Interests, Personal, Stocks/Shares: Gritstone, Relay Therapeutics. T. André: Financial Interests, Personal, Advisory Board, Advosiry Board on February 12, 2021: Astellas pharma; Financial Interests, Personal, Advisory Board, Advisory Board on February 2021: Kaleido Biosciences; Financial Interests, Personal, Invited Speaker, and advisory board 2021: Amgen; Financial Interests, Personal, Invited Speaker, Ivited speaker in a symposuim december 2020: AstraZeneca; Financial Interests, Personal, Advisory Board, and consultant fees and consultant contract 2021 and 2022: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, Advisory board in Janaury 2020 : Clovis; Financial Interests, Personal, Advisory Board, Advisory board in january 2020: Gritstone Oncology; Financial Interests, Personal, Advisory Board, Advisory board 2020: Haliodx; Financial Interests, Personal, Advisory Board, and consultant fees/consultant contract and invited speaker: MSD Oncology; Financial Interests, Personal, Invited Speaker, and other: Pierre Fabre; Financial Interests, Personal, Invited Speaker, in an symposuim in 2020: Roche; Financial Interests, Personal, Invited Speaker, in a meeting in 2019: Ventana; Financial Interests, Personal, Invited Speaker, In a educational meeting in 2019: Sanofi; Financial Interests, Personal, Advisory Board, in a symposuim in 2020: Servier; Financial Interests, Personal, Advisory Board, Consultant with personnal fees and invited speaker: Servier; Financial Interests, Personal, Advisory Board, in 2019: GSK; Financial Interests, Personal, Invited Speaker, in 2020 and 2021: GSK; Financial Interests, Personal, Invited Speaker, Virtual symposuimLecture: 1 MSI-H CRC: Implementation of Immunotherapy in clinical practice (30 minutes) – (this will be pre-recorded)Q&A – Live Q&A – (10 minutes) (on July 2, 2021): MSD Oncology; Financial Interests, Personal, Invited Speaker, June 2022 : Sanofi; Financial Interests, Personal, Advisory Board, Contract 2021, 2022, 2023: Merck & Co., Inc; Financial Interests, Personal, Advisory Board, Contrat 2019, 2020, 2021, 2022: BMS; Financial Interests, Personal, Advisory Board, Contract 2021: Gritstone Oncologie; Financial Interests, Personal, Invited Speaker, June 2022 and June 2023 during ESMO GI meeting: Seagen; Financial Interests, Personal, Writing Engagement, Contract of consulting 2021 and 2022 and 2023: MSD Oncology; Financial Interests, Personal, Advisory Board, September 2022: GSK, Seagen; Financial Interests, Personal, Writing Engagement, Contract of consulting 2022 and 2023: GSK; Financial Interests, Personal, Writing Engagement, Contract of consulting 2022: Nordic Pharma; Financial Interests, Personal, Invited Speaker, October 2022: Merck Serono; Financial Interests, Personal, Other, Educationnal in 2022: Roche; Financial Interests, Personal, Other, Contract of consulting 2020, 2021, 2022, 2023: Servier; Financial Interests, Personal, Advisory Board, 2023: Aptide Health, Glilead; Financial Interests, Institutional, Other, Investigator and scientific comitee president: Gercor Academic group; Financial Interests, Institutional, Coordinating PI, PI Garnet study: GSK; Financial Interests, Institutional, Coordinating PI, Keynote 164 and 171 and 811 and C08: MSD; Financial Interests, Institutional, Coordinating PI, BMS CA209-8HW, BMS CA209-142, BMS CA209-577: BMS; Financial Interests, Institutional, Coordinating PI, SPOTLIGHT study: Astellas; Financial Interests, Personal, Steering Committee Member, and internationnal PI (trial chair Solstice study): Servier; Financial Interests, Personal, Steering Committee Member, MOUNTAINEER and MOUNTAINEER-03 study (PI for France) 2022, 2023: Seagen; Non-Financial Interests, Member of Board of Directors, Investigator: Gercor group; Non-Financial Interests, Member of Board of Directors, President since october 2022: ARCAD Foundation. A. Marabelle: Financial Interests, Personal, Advisory Board: Gritstone, Innate Pharma, Neogene, Deka Biosciences, Hotspot Therapeutics, Johnson & Johnson, Depth Charge, Bioline Rx, Clover Biopharmaceuticals, Grey Wolf Therapeutics, Lytix Biopharma, RedX Pharma, HiFiBiO Therapeutics, ImCheck Therapeutics, Shattuck Labs, Marengo Therapeutics, PegaOne; Financial Interests, Personal, Other, Associate Editor: European Journal of Cancer; Financial Interests, Personal, Stocks/Shares: HiFiBiO Therapeutics, Deka Biosciences, HotSpot Therapeutics, Shattuck Labs; Financial Interests, Institutional, Research Grant: BMS, AstraZeneca, Sanofi; Financial Interests, Institutional, Coordinating PI: IMCheck, SOTIO, Roche/Genentech, MSD, BMS, OSE Immunotherapeutics, EISAI, Pierre Fabre, Adlai Nortye, Molecular Partners; Financial Interests, Steering Committee Member: Roche; Financial Interests, Institutional, Funding: Transgene; Non-Financial Interests, Other, Associate Editor: IOTECH Journal; Non-Financial Interests, Institutional, Product Samples: BMS, IDERA, MSD, Transgene; Non-Financial Interests, Leadership Role: Société Française d'Immunothérapie des Cancers; Non-Financial Interests, Member: Society for Immunotherapy of Cancer, American Association for Cancer Research, American Society for Clinical Oncology; Other, Other, Consultant: Third Rock Ventures, Guidepoint; Other, Other, Advisor: Medicxi. All other authors have declared no conflicts of interest.