1021MO - Safety and efficacy of etigilimab (anti-TIGIT) with nivolumab (anti-PD1) in recurrent/advanced solid tumors

Background

Etigilimab (etig), a humanized IgG1 mAb, blocks TIGIT interaction with PVR (poliovirus receptor) resulting in immune cell activation with tumor cell killing. ACTIVATE, an open-label phase 1b/2 study is evaluating further efficacy, safety, tolerability, and PK/PD of etig+nivolumab (nivo). This is an additional update in select cohorts from ACTIVATE, for tumors less responsive to anti-PD-(L)1 monotherapy.

Methods

Subjects with advanced/metastatic solid tumors and no curative/standard of care therapies are given IV etig+nivo Q2W. Cohorts enrolled include gynecological malignancies: endometrial cancer (EC post-front-line platinum), EC (2-3 prior lines), PD-(L)1+ checkpoint-inhibitor-naïve (CPI-n) cervical cancer, rare cancers (germ cell tumor (GCT), sarcoma, uveal melanoma) and ovarian cancer (post-front-line platinum). The primary endpoint is investigator assessed ORR by RECIST 1.1. Secondary endpoints include response duration and safety.

Results

Of 76 safety evaluable subjects, eight subjects showed treatment related adverse events (TRAEs) > than Grade 2. Only one TRSAE was observed. There were no treatment related deaths. See Table for efficacy data for select cohorts. Of 40 evaluable patients presented, 3 CRs, 7 PRs and 11 SDs beyond 120 days were noted. Seven subjects showed clinical benefit for ≥ 1 yr. 1. BOR at treatment termination or by 4 May 2023 for on study patients. 2. mixed response, continued treatment, PD-RECIST 1.1. Table: 1021MO

Best Observed Response (BOR)¹ - Days on study

Conclusions

Etig in combination with nivo is safe and well tolerated. Preliminary efficacy data of prolonged on study duration with clinical benefit in immune resistant tumors supports continued evaluation in tumor types not typically responsive to anti-PD(L)1 monotherapy.

Clinical trial identification

NCT04761198.

Editorial acknowledgement

Legal entity responsible for the study

Authors and Mereo BioPharma.

Funding

Mereo BioPharma.

Disclosure

M. Mckean: Financial Interests, Institutional, Other, Consulting: Pfizer, Castle Biosciences, Eisai, IQVIA, Merck, Moderna; Financial Interests, Personal, Other, Consulting: iTeos; Financial Interests, Institutional, Research Grant: Acentage Pharma Group, Bicycle Therapeutics, Dragonfly Therapeutics, Epizyme, Exelixis, Genentech, GSK, Ideaya Biosciences, Ikena Oncology, Infinity Pharmaceuticals, Jacobio Pharmaceuticals, Moderna, NBE Therapeutics, Novartis, Oncorus, Plexxicon, Prelude Therapeutics, Regeneron, Sapience Therapeutics, Seattle Genetics, Tizona Therpeutics, Tmunity Therapeutics, TopAlliance Biosciences, Aadi Biosciences, Alpine Immune Sciences, Arcs Biosciences, Arvinas, ASCO, Astellas, Bayer, BioMed Valley Discoveries, BioNTech, C4 Therapeutics, EMD Serono, Erasca, Foghorn Therapeutics, G1 Therapeutics, Gilead Sciences, ImmVira Pharma, Kechow Pharma, Kezar Life Sciences, Kinnate BioPharma, MedImmune, Mereo BioPharma, Metabomed, Nektar, OncoC4, PACT Pharma, Pfizer, Poseida, Pyramid Biosciences, Scholar Rock, Synthrox, Takeda Pharmaceuticals, Teneobio, Tempest Therapeutics, Xilio. E.E. Dumbrava: Financial Interests, Institutional, Other, Research/grant funding: Bayer HealthCare Pharmaceuticals, Immunocore Ltd, Amgen, Aileron Therapeutics, Compugen Ltd, Gilead, BOLT Therapeutics, Aprea Therapeutics, Bellicum, PMV Pharma, Triumvira, Seagen Inc, Mereo BioPharma 5 Inc, Sanofi, Rain Oncology, Astex Therapeutics, Sotio, Mersana Therapeutics, Poseida, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: PMV Pharma; Financial Interests, Personal, Advisory Board: BOLT Therapeutics, Mersana Therapeutics, Orum Therapeutics, Summit Therapeutics. O. Hamid: Financial Interests, Personal, Advisory Board: Alkermes, Amgen, BMS, Bactonix, BeiGene, Bioatla, Esai, GSK, Georgiamune, GigaGen, Grit Bio, IO Biotech, Idera, Idera, Immunocore, Incyte, Instil Bio, Iovance, Janssen, KSQ, Merck, Nextcure, Novartis, Obsidian, Pfizer, Roche Genentech, SEAGEN, Sanofi / Regeneron, Tempus, Vial, Zelluna; Financial Interests, Personal, Invited Speaker: BMS, Immunocore, Novartis, Pfizer, Sanofi / Regeneron; Financial Interests, Personal, Stocks/Shares: Bactonix; Financial Interests, Institutional, Local PI: Aduro, Akeso, Amgen, Arcus, BMS, Bioatla, CytomX, Exelixis, GSK, Idera, Immunocore, Incyte, Iovance, Merck, Merck Serono, Moderna, Nextcure, Novartis, Pfizer, Roche Genentech, Rubius, Seagen, Sanofi / Regeneron, Torque, Zelluna. P. Merriam: Financial Interests, Institutional, Local PI: Mereo, SpringWorks. W. Feely: Financial Interests, Personal, Full or part-time Employment: Mereo BioPharma; Financial Interests, Personal, Full or part-time Employment, former employee: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Mereo BioPharma; Non-Financial Interests, Personal, Full or part-time Employment: Mereo BioPharma. A. Green: Financial Interests, Personal, Other, Consultancy: Merck; Financial Interests, Institutional, Research Funding: Eli Lilly, Mereo BioPharma. U.N. Vaishampayan: Financial Interests, Personal, Advisory Board, consultant: BMS; Financial Interests, Personal, Advisory Board: Bayer, Gilead, Pfizer, Merck, Exelixis, Sanofi, Novartis, Alkermes; Financial Interests, Personal, Invited Speaker: Exelixis; Financial Interests, Institutional, Research Grant, Investigator initiated trial supported by Merck: Merck; Non-Financial Interests, Member of Board of Directors: Michigan Society of Hematology/Oncology. K.N. Moore: Financial Interests, Personal, Advisory Board: AstraZeneca, Aravive, Alkemeres, Blueprint pharma, Eisai, EMD Serono, GSK/Tesaro, Genentech/Roche, Hengrui, Immunogen, IMab, mereo, myriad, caris, Mersana, Novartis, Novocure, OncXerna, OncoNova, tarveda, VBL Therapeutics, Clovis, Caris, Lilly, Novartis, Pannavance, Verastem, Zentalis, Merck; Financial Interests, Institutional, Advisory Board, advisory board work for gynecologic trial: Aadi; Financial Interests, Institutional, Advisory Board, work on clinical trial and planning for next trial: Duality; Financial Interests, Personal, Full or part-time Employment: GOG Partners Associate Director; Financial Interests, Institutional, Full or part-time Employment: NRG Ovarian Cancer Chair; Financial Interests, Personal, Member of Board of Directors, not reimbursed: ASCO; Financial Interests, Institutional, Member of Board of Directors, not reimbursed: GOG Foundation; Financial Interests, Personal, Royalties: UP to Date; Financial Interests, Institutional, Coordinating PI, international CO-PI, local site PI: AstraZeneca; Financial Interests, Institutional, Coordinating PI: Immunogen, GSK/Tesaro, PTC Therapeutics, duality; Financial Interests, Institutional, Local PI: Lilly, Daiichi Sankyo, Regeneron, Artios, Bolt, verastem; Non-Financial Interests, Member of Board of Directors: GOG. S. Weroha: Financial Interests, Institutional, Royalties: Mayo Clinic. S. Krishnan: Financial Interests, Personal, Full or part-time Employment: Mereo BioPharma; Financial Interests, Personal, Full or part-time Employment, former employee: Merck, AstraZeneca, Bristol Myers Squibb. A. George: Financial Interests, Personal, Advisory Board, Advisory board attendance: AstraZeneca; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Other, Editorial and research review: Roche. All other authors have declared no conflicts of interest.