LBA50 - Three-year survival with tebentafusp in previously untreated metastatic uveal melanoma in a phase III trial

Background

Metastatic uveal melanoma (mUM) has a historically poor 1-yr overall survival (OS) rate of 52%. Tebentafusp (tebe), a bispecific (gp100 x CD3) ImmTAC, is approved for adult HLA-A*02:01+ patients (pts) with unresectable or mUM. In the primary analysis of the Phase (Ph) 3 IMCgp100-202 study in previously untreated mUM [NCT03070392], tebentafusp significantly improved OS compared to investigator’s choice (IC) [HR 0.51] with a 1-yr OS rate of 73% versus 59%, respectively. Deeper ctDNA reductions were associated with longer OS. Here we present the 3-yr updated analyses of the Ph3 study.

Methods

In this randomized, open-label, Ph3 trial, HLA-A*02:01+ first-line mUM pts were randomized 2:1 to receive tebe or IC of pembrolizumab, ipilimumab or dacarbazine, stratified by LDH. Primary endpoint was OS. Secondary endpoints included overall response rate (ORR), progression free survival (PFS) and disease control rate (DCR) and safety. An exploratory endpoint was ctDNA reduction.

Results

378 pts were randomized to tebe (252) or IC, including pembrolizumab (103), ipilimumab (16) or dacarbazine (7). After a minimum follow-up of 36 months, the estimated 3-yr OS of tebe was 27% (95% CI 22-33%) vs 18% (95% CI 11-25%) for IC with maintained separation of the OS KM curves. The OS benefit of tebe was also observed in pts with known poor prognostic factors in the metastatic setting. 1-yr and 2-yr PFS rates were 17% vs 9% and 8% vs 3%, for tebe vs IC, respectively. ORR remained in favor of tebe vs IC (11% vs 5%). A third of tebe responders were still in response at 18 months. The DCR rates (CR/PR/SD ≥12 weeks) were 46% for tebe and 27% for IC. Of 45 ctDNA evaluable pts in the tebe arm who cleared their ctDNA by week 9, 32 (71%) survived ≥2 yrs and 17 (38%) survived ≥3 yrs. No new safety signals were identified. The rate of treatment discontinuation due to related AEs continued to be lower in the tebe arm (2% vs 5%). There were no treatment related deaths.

Conclusions

This is the longest OS follow-up in a randomized trial in mUM. Tebentafusp continues to provide long-term survival benefit in first line HLA-A*02:01+ pts, with estimated 3-yr OS rate of 27%, further solidifying tebentafusp as first line standard of care in this population.

Clinical trial identification

NCT03070392.

Editorial acknowledgement

Legal entity responsible for the study

Immunocore Ltd.

Funding

Immunocore Ltd.

Disclosure

S. Piperno-Neumann: Financial Interests, Personal, Advisory Board: Immunocore, Pierre Fabre, Atlanthera. J.C. Hassel: Financial Interests, Personal, Invited Speaker: BMS, Novartis, sanofi, MSD, Sunpharma, Almirall, Roche, Amgen, GSK, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, Pierre Fabre, Sunpharma, GSK; Financial Interests, Institutional, Advisory Board: Novartis, BMS, Immunocore, Nektar, Philogen; Financial Interests, Institutional, Research Grant: BMS, Sunpharma; Financial Interests, Institutional, Invited Speaker: Philogen, BMS, Genentech, Immunocore, Immunocore, 4SC, Novartis, BioNTech, Idera, Iovance, Nektar, Pierre Fabre, Regeneraon, Sanofi; Non-Financial Interests, Leadership Role: DeCOG; Non-Financial Interests, Member: ASCO. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfizer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Member of Board of Directors: Polish Society of Surgical Oncology; Non-Financial Interests, Member of Board of Directors, President: Polish Oncological Society. M. Schlaak: Financial Interests, Personal, Advisory Board: Bristol-Myers Squibb, Novartis, Merck/MSD, Roche, Pierre Fabre, Kyowa Kirin, Immunocore, Sanofi Genzyme; Financial Interests, Personal, Other, Travel expenses: Sun Pharma. M.O. Butler: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, Bristol Myers Squibb, Novartis, Sanofi, Pfizer, Adaptimmune, GSK, Immunocore, EMD Serono, Sun Pharma; Financial Interests, Personal and Institutional, Research Grant: Merck; Financial Interests, Personal, Research Grant: Takara Bio; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Novartis, Sanofi, Adaptimmune, Immunocore, Regeneron, Lilly, Amgen, OncoSeq. R.J. Sullivan: Financial Interests, Personal, Advisory Board: Merck, Novartis, Bristol Myers Squibb, Eisai, Iovance, Oncosec, Pfizer, Replimmune, Marengo; Financial Interests, Personal, Royalties: Up-to-date; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Invited Speaker: GSK, Pfizer, Sanofi, Moderna, Roche-Genentech, BiomedValley DIscoveries, Astex, Compugen, Beigene, Novartis, Rubius, Alkermes, Simcha Therapeutics, OnKure, Synthekine, Marengo. R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaviVAX SA, touchIME, T3 Pharma, Pfizer, Simcere. J.M. Kirkwood: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Amgen, Harbour BioMed, ISTARI Oncology, Scopus BioPharma, Pfizer, AXIO Research, Immunocore, Natera, DermTech, Ankyra Therapeutics, Becker Pharmaceutical Consulting, Fenix Group International, IQVIA, Merck, Replimune, SR One Capital Management, Iovance Biotherapeutics, Checkmate Pharmaceuticals, OncoSec, OncoCyte, Cancer Network, Takeda, Applied Clinical Intelligence, PATHAI, Magnolia Innovation, iOnctura, Jazz Pharmaceuticals, Regeneron; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Checkmate Pharmaceuticals, Bristol-Myers Squibb, Regeneron, Ankyra Therapeutics, Iovance Biotherapeutics; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Institutional, Research Funding: Amgen, Bristol-Myers Squibb, Checkmate Pharmaceuticals, Immunocore, Iovance Biotherapeutics, Novartis, Immvira, Harbour BioMed, Takeda, Verastem, Lion Biotechnologies. M. Orloff: Financial Interests, Personal, Speaker’s Bureau: Bristol-Myers Squibb; Financial Interests, Personal, Speaker, Consultant, Advisor: IDEAYA Biosciences, Immunocore, Trisalus Life Sciences, Delcath Systems; Financial Interests, Institutional, Research Funding: Bristol-Myers Squibb, Immunocore, Delcath Systems, Plexxikon, IDEAYA Biosciences, Linnaeus Therapeutics. J.J. Sacco: Financial Interests, Personal, Speaker, Consultant, Advisor: Immunocore, Bristol Myers Squibb, MSD, Delcath, Amgen; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, MSD, Pierre Fabre; Financial Interests, Institutional, Research Grant: Immunocore, Bristol Myers Squibb, MSD, Amgen, AstraZeneca, Replimune. S. Ochsenreither: Financial Interests, Personal, Advisory Board: MSD, BMS, Janssen, Ipsen, Immunocore, Genemab, Pfizer; Financial Interests, Personal, Invited Speaker: MSD, Merck, Immunocore, Janssen; Financial Interests, Personal, Other, Support for travel / meeting: Janssen, Pfizer; Financial Interests, Personal, Invited Speaker, Patent of T-cell therapy target: Fred Hutchinson cancer Research Center. A.M. Joshua: Financial Interests, Personal, Stocks/Shares: Pricillium Therapeutics; Financial Interests, Institutional, Invited Speaker: Neolukin, Janssen, Ipsen, AstraZeneca, Sanofi, Noxopharm, Iqvia, Pfizer, Novartis, Bristol-Myers Squibb, Merck Serono, Eisai; Non-Financial Interests, Advisory Role: Bristol-Myers Squibb, Janssen, Merck, Mayne, Roche, Bayer, Macrogenics, Pfizer, AstraZeneca, Corvus, Eli-Lilly. B. Curti: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: Biomarkers for OX40 response; Financial Interests, Personal, Other, Honoraria: Clinigen Group, Sanofi; Financial Interests, Institutional, Research Funding: Bristol-Myers Squibb, Clinigen Group. R.D. Carvajal: Financial Interests, Personal, Speaker, Consultant, Advisor: Alkermes, Bristol Myers Squibb, Castle Biosciences, Delcath, Eisai, Hengrui, Ideaya, Immunocore, InxMed, Iovance, Merck, Novartis, Oncosec, Pierre Fabre, PureTech Health, Sanofi Genzyme, Trisalus; Financial Interests, Personal, Speaker’s Bureau: Regeneron; Financial Interests, Personal, Advisory Board: Aura Biosciences, Chimeron, Rgenix. 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, Invited Speaker: 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. L. Collins: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. C. Holland: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore, Amgen, MacroGenics. P. Nathan: Financial Interests, Personal, Advisory Board: BMS, Immunocore, Novartis, Merck, Pfizer, 4SC, IDEAYA; Financial Interests, Institutional, Other, research support: Immunocore; Financial Interests, Personal, Invited Speaker: novartis, 4SC; Financial Interests, Institutional, Invited Speaker: BMS, Novartis, Ipsen, Immunocore, Merck, Pfizer. All other authors have declared no conflicts of interest.