Abstract 843P
Background
The phase (Ph)3 IMCgp100-202 trial (NCT03070392) of tebentafusp (tebe) in untreated metastatic uveal melanoma (mUM) demonstrated improved overall survival (OS), HR=0.51. In the Ph2 IMCgp100-102 trial (Study 102; NCT02570308) in previously treated mUM, the estimated 2-yr and 3-yr tebe OS rates were 37% and 24% compared to 15% and 9%, respectively, from a meta-analysis (Rantala 2019). The OS benefit is not explained by RECIST responses alone. We describe the characteristics of tebe treated pts with long-term survival (OS ≥ 2 yrs) in Study 102.
Methods
127 pts with 2L+ mUM received tebe during the expansion phase of Study 102, where treatment beyond initial RECIST progression (TBP) was allowed. The association between OS and baseline (BL) covariates, on-treatment RECIST response, baseline tumor biopsy and ctDNA changes were assessed (31Mar2021 data cut-off).
Results
With median follow-up of 29.9 months, 33% (42/127) of pts had OS ≥ 2 yrs, 79% of whom received TBP. 5 of 6 pts with PR were alive ≥ 2 yrs. 41% (25/61) of pts with best response of PD had OS ≥ 1 yr, including 10 pts with OS ≥ 2 yrs. In a multivariate analysis of BL covariates, LDH ≤ ULN and ALP ≤ ULN were most strongly associated with OS ≥ 2 yrs. Lower BL serum ctDNA levels and a low tumor M2 macrophage:CD3 T cell ratio were strongly associated with OS ≥ 2 yrs. BL gp100 expression, prior IO therapy (including anti-PD1 +/- ipilimumab), time from initial diagnosis or metastatic disease, or size of largest liver lesion were not significant predictors of OS ≥ 2 yrs. 20% (14/69) of pts with largest liver lesion of ≥ 3 cm had OS ≥ 2 years. ctDNA reduction (≥ 0.5 log) or clearance by Wk 9 were associated with long OS. Of 25 pts with OS ≥ 2 yrs and evaluable ctDNA, 52% (13/25) had ≥ 0.5 log ctDNA reduction, of whom 8 had ctDNA clearance. Most of the 13 pts had best RECIST response of PD or SD.
Conclusions
The strongest baseline predictors of OS ≥ 2 yrs on tebe were low serum LDH, ALP and ctDNA and, in tumors, a low M2 macrophage:CD3 T cell ratio. Other BL covariates, e.g., size of largest liver lesion, were not significant predictors. ctDNA reduction/clearance may be a better early surrogate of long OS than radiographic response.
Clinical trial identification
NCT02570308.
Editorial acknowledgement
Legal entity responsible for the study
Immunocore Ltd.
Funding
Immunocore Ltd.
Disclosure
T. Sato: Financial Interests, Personal, Advisory Role: Immunocore, Castle Biosciences; Financial Interests, Institutional, Research Grant: Immunocore, Verastem; Financial Interests, Personal, Other, Expenses: Castle Biosciences. A.P. Ikeguchi: Financial Interests, Institutional, Research Grant: Dynavax, Immunocore, Merck, GSK/Sarah Cannon, Neon Therapeutics/Sarah Cannon, Checkmate Pharmaceuticals. P. Nathan: Financial Interests, Personal, Advisory Board: BMS, Immunocore, Novartis, Merck, Pfizer, 4SC; 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. R.D. Carvajal: Financial Interests, Personal, Other, Consulting: Merck, Castle Biosciences, Immunocore, PureTech Health, Sorrento Therapeutics, InxMed, Pierre Fabre, TriSalus Life Sciences, Iovance Biotherapeutics, Oncosec, Regeneron, Sanofi Genzyme, Bristol Myers Squibb/Medarex, Ideaya, Novartis; Financial Interests, Personal, Advisory Board: Aura Biosciences, Chimeron Bio, Rgenix; Financial Interests, Institutional, Research Grant: Amgen, Astellis, Astrazeneca, Bristol Myers Squibb, Corvus , Ideaya, Immunocore, Iovance, Merck, Mirati, Novartis, Pfizer, Plexxikon, Roche/Genentech, Regeneron; Financial Interests, Institutional, Other, Consulting: Alkermes, Delcath, Eisai. A.N. Shoushtari: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Immunocore; Financial Interests, Personal, Royalties: UptoDate; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Immunocore, Polaris, Xcovery, Pfizer, Novartis, Targovax ASA, Checkmate Pharmaceuticals; Non-Financial Interests, Member: ASCO. T.F. Gajewski: Financial Interests, Personal, Advisory Board: Jounce, Pyxis, FogPharma, Amgen, Merck, Adaptimmune, Allogene, CataLym, Samyang; Financial Interests, Personal, Stocks/Shares: Jounce, Evelo; Financial Interests, Personal, Ownership Interest: Pyxis; Financial Interests, Personal, Invited Speaker: Evelo; Financial Interests, Institutional, Invited Speaker: Merck; Financial Interests, Institutional, Research Grant: BMS, Pyxis, Bayer. 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. M. Rioth: Financial Interests, Personal, Full or part-time Employment: Syapse; Financial Interests, Personal, Stocks/Shares: Syapse. S. Leyvraz: Financial Interests, Personal, Advisory Role: Bayer, Immunocore; Financial Interests, Personal, Other, Expenses: Bayer. G.A. Daniels: Other, Personal, Advisory Role: Immunocore. L. Hernandez-Aya: Financial Interests, Personal, Advisory Role: Massive Bio, Bristol Myers Squibb, Castle Biosciences; Financial Interests, Personal, Speaker’s Bureau: Sanofi/Regeneron; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Regeneron, Immunocore, Merck, Polynoma, Corvus Pharmaceuticals, Roche/Genentech, Merck Serono, Amgen, MedImmune, Takeda, Moderna Therapeutics, Foghorn Therapeutics; Financial Interests, Personal, Other, Expenses: Sanofi/Regeneron, Bristol Myers Squibb, Castle Biosciences. D.B. Johnson: Financial Interests, Personal, Advisory Board: BMS, Catalyst, Iovance, Jansen, Mallinckodt, Merck, Mosaic, Novartis, Pfizer, Oncosec, Targovax; Financial Interests, Personal, Research Grant: BMS, Incyte. K. Kim: Financial Interests, Personal, Advisory Role: Genentech/Roche, Bristol Myers Squibb, Jazz Pharmaceuticals, Eisai, Sanofi/Regeneron, AVEO, Sanofi/Regeneron; Financial Interests, Personal, Speaker’s Bureau: Sanofi/Regeneron; Financial Interests, Personal, Stocks/Shares: Cryoport, Arvinas, Arvinas; Financial Interests, Personal, Stocks/Shares, Family Member: Cryoport; Financial Interests, Institutional, Research Grant: GlaxoSmithKline, Novartis, Bristol Myers Squibb, Merck, Regeneron; Financial Interests, Personal, Research Grant: Amgen, Iovance Biotherapeutics, Immunocore, Immunocore, Astex Pharmaceuticals, Nektar. J.M. Piulats Rodriguez: Financial Interests, Personal, Advisory Board: Janssen, Astellas, Roche, BMS, MSD, BeiGene, VCN, AstraZeneca; Financial Interests, Personal and Institutional, Research Grant: BMS, Pfizer, Janssen, BeiGene, Mirati. C.L. Cowey: Other, Personal, Advisory Role: Immunocore. S. Lockwood: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. L. Collins: Financial Interests, Personal, Stocks/Shares: Immunocore; Financial Interests, Personal, Full or part-time Employment: Immunocore. O. Karakuzu: Financial Interests, Personal, Stocks/Shares: Immunocore; Financial Interests, Personal, Full or part-time Employment: Immunocore. J.J. Sacco: Financial Interests, Personal, Other, Honoraria: Immunocore, Pierre Fabre, Novartis; Financial Interests, Institutional, Advisory Role: Immunocore; Financial Interests, Personal, Advisory Role: Delcath Systems, MSD, BMS, Immunocore; Financial Interests, Institutional, Research Grant: Astrazeneca, Immunocore, Replimune, BMS; Financial Interests, Personal, Other, Expenses: BMS, MSD. M.O. Butler: Financial Interests, Personal, Other, Honoraria: Roche, Merck, Bristol Myers Squibb, Novartis; Financial Interests, Personal, Advisory Role: Merck, Bristol Myers Squibb, Novartis, Immunovaccine, Immunocore, Adaptimmune, EMD Serono, GlaxosmithKline, Genzyme, Sanofi, LaRoche Posay, Sun Pharma, Instil Bio, Iovance Biotherapeutics, Pfizer; Financial Interests, Personal, Research Grant: Merck, Takara Bio; Financial Interests, Personal, Expert Testimony: Merck.