Abstract 884TiP
Background
Immune checkpoint inhibitors (ICIs) targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) have improved overall survival (OS) in patients (pts) with advanced melanoma, and neoadjuvant ICIs can induce tumor regression in pts with resectable melanoma. Targeting other co-inhibitory receptors, such as lymphocyte activation gene-3 (LAG-3) or T cell immunoglobulin and ITIM domain (TIGIT), or combining agents targeting multiple immune evasion mechanisms may enhance antitumor activity.
Trial design
MORPHEUS-MELANOMA (NCT05116202) is a phase 1b/2 multicenter, randomized, open-label, umbrella study in pts with treatment-naive, resectable stage III (Cohort 1) or previously treated stage IV (Cohort 2) melanoma. Cohort 1 pts will be randomized to receive 6 weeks of neoadjuvant treatment in 1 of 3 experimental arms (RO7247669 [bispecific anti–PD-1/anti–LAG-3], atezolizumab [anti–PD-L1] + tiragolumab [anti–TIGIT], or RO7247669 + tiragolumab) or a comparator arm (nivolumab 3 mg/kg [anti–PD-1] + ipilimumab 1 mg/kg [anti–CTLA-4]). Pts will be stratified by region (Australia vs Rest of World) and lactate dehydrogenase (≤ vs > ULN). Cohort 2 pts will receive experimental treatment with RO7247669 + tiragolumab until unacceptable toxicity or loss of clinical benefit; new arms may be added as new treatments become available. The study will enroll ∼61-191 pts, including ≥ 6 pts in a safety run-in phase in Cohort 2. Experimental arms will enroll in a preliminary phase (20 pts per arm) and an expansion phase (20 additional pts per arm). Primary end point for Cohort 1 is pathologic response rate at surgery by independent review; secondary end points are pathologic response by local assessment, event-free survival, recurrence-free survival, OS, objective response rate (ORR), and safety. Primary end point for Cohort 2 is ORR by investigator assessment; secondary end points are progression-free survival, OS, duration of response, disease control rate, and safety. Biopsies will be collected at baseline, in cycle 2 (both cohorts), and at surgery (Cohort 1). The study is currently enrolling, with 21 sites planned in Australia, Europe, and USA.
Clinical trial identification
NCT05116202.
Editorial acknowledgement
Editorial assistance was provided by Melanie Sweetlove, MSc (ApotheCom, San Francisco, CA, USA), and was funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG (Sandoz Company), Merck Sharpe & Dohme (Australia) Pty Limited, Novartis Pharma AG, OncoSec Medical Australia, Pierre Fabre, Provectus Australia, Qbiotics Group Limited, Regeneron Pharmaceuticals Inc; Financial Interests, Personal, Advisory Board, Consultant Advisor: Highlight Therapeutics S.L. R. Amaria: Financial Interests, Personal, Advisory Board: Iovance Biotherapeutics, Novartis, Bristol Myers-Squibb; Financial Interests, Institutional, Invited Speaker: Merck, Bristol Myers Squibb, Novartis, Iovance. A. Tarhini: Financial Interests, Personal, Advisory Board: Bristol Myers Squib, Genentech/Roche, Easai, Instil Bio, Clinigen, Regeneron, Sanofi-Genzyme, Novartis, Partner Therapeutics, BioNTech, Merck; Financial Interests, Personal and Institutional, Invited Speaker: Bristol Myers Squib; Financial Interests, Institutional, Invited Speaker: Genentech-Roche, Nektar, Checkmate, InflaRx; Financial Interests, Institutional, Research Grant: Regeneron, Sanofi-Genzyme, Clinigen, Acrotech, Pfizer, OncoSec. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Pfizer/Array, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna, Bio-AI Health; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR; Other, Travel Support: MSD. E. Cha: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. O. Cirovic: Financial Interests, Personal, Full or part-time Employment: Roche. D. Cotting: Financial Interests, Personal, Full or part-time Employment: Roche. V. Teichgräber: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. C.U. Blank: Financial Interests, Institutional, Advisory Board: BMS, MSD, Roche, Novartis, GSK, AZ, Pfizer, Lilly, GenMab, Pierre Fabre; Financial Interests, Personal, Expert Testimony: Third Rock Ventures; Financial Interests, Personal, Stocks/Shares: Uniti Cars, co-founder Immagene BV; Financial Interests, Institutional, Invited Speaker: BMS, Novartis, NanoString, 4SC.