1129P - Effect of subsequent therapies including checkpoint inhibitors on overall survival in a phase III randomized trial of tebentafusp in first-line metastatic uveal melanoma: Long-term follow-up

Background

Tebentafusp (tebe) is a bispecific consisting of an affinity-enhanced T cell receptor fused to an anti-CD3 effector that can redirect T cells to target gp100+ cells. Tebe significantly improved overall survival (OS) compared to investigator’s choice of pembrolizumab, ipilimumab or dacarbazine (HR 0.51) in first line (1L) mUM [NCT03070392]. Here we evaluated the impact of subsequent therapy on long-term survival.

Methods

Analyses were conducted on HLA-A*02:01+ patients with first line mUM recruited to the randomized phase III study (Study 202, N=378). Crossover to tebe was not permitted until the planned interim analysis demonstrated significant OS benefit. Inverse probability of censoring weighting (IPCW) was used to compare the tebentafusp and investigator’s choice (IC) arms by removing the effects of subsequent therapies (any versus CPI only). OS from the start of subsequent therapy was compared between arms using Cox regression models adjusted for prognostic baseline covariates.

Results

After a median follow-up of 37.8 months, a similar percentage of patients, ∼ 62%, received subsequent therapy in each arm. Median time to first subsequent therapy was longer for tebe pts (6.4 mo) vs. IC pts (4.5 mo). The most frequent subsequent therapy was CPI in both arms (received by 49% of tebe pts and 34% of IC pts); 17% of IC pts received subsequent tebe. When adjusting for the effect of subsequent therapy (any or CPI), the OS benefit from the ITT analysis was maintained. In an analysis of survival from the start of any first subsequent therapy, prior tebe patients tended to have longer OS compared to prior IC patients, HR (95% CI) 0.75 (0.55, 1.04). This difference was also seen when restricting to patients who received subsequent CPI therapy, HR (95% CI) 0.72 (0.48, 1.09).

Conclusions

Based on IPCW analysis, the OS benefit in first line HLA-A*02:01+ mUM patients is predominantly due to tebentafusp and not due to subsequent therapy. This reinforces the use of tebentafusp in the first line setting. Updated data with a minimum 3 years of follow-up will be presented. 1. Yang J. et al. ASCO 2019 , J. Clin Oncol 37:15_suppl, 9592.

Clinical trial identification

NCT03070392.

Editorial acknowledgement

Legal entity responsible for the study

Immunocore Ltd.

Funding

Immunocore Ltd.

Disclosure

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. C. Watkins: Financial Interests, Personal, Speaker, Consultant, Advisor: Celgene/Bristol Myers Squibb, Roche, Immunocore, Ascelia, Humanigen, Astellas Pharma, F2G, Amylyx, Kite/Gilead, Novo Nordick, Neurovalens, Medical Developments International, Servier, EQRx. 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; Financial Interests, Institutional, Speaker, Consultant, Advisor: Regeneron, Sanofi Genzyme, Trisalus Clinical; Financial Interests, Institutional, Advisory Board: Aura Biosciences, Chimeron, Rgenix. A.N. Shoushtari: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Immunocore, Novartis; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Immunocore, Polaris, Xcovery, Pfizer, Novartis, Targovax ASA, Checkmate Pharmaceuticals, Linnaeus Therapeutics, Prelude Therapeutics; Financial Interests, Personal, Invited Speaker: Foghorn Therapeutics; Non-Financial Interests, Member: ASCO. 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. 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. J. Gama: Financial Interests, Personal, Full or part-time Employment: Immunocore. 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.