Abstract 1013P
Background
Tebentafusp 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. In a randomized phase III study of tebentafusp in 1L metastatic uveal melanoma (mUM) [NCT03070392], tebentafusp demonstrated OS benefit vs. investigator’s choice including checkpoint immunotherapy (IO). As checkpoint inhibitors (CPI) may alter the tumor immune profile, we explored the impact of prior IO treatment on clinical outcomes (efficacy and on-target adverse events) and immune phenotype in a phase II study of 2L+ patients with mUM treated with tebentafusp [NCT02570308].
Methods
127 HLA-A*02:01+ 2L+ mUM patients were treated weekly with tebentafusp following intra-patient dose escalation: 20mcg dose 1, 30mcg dose 2 and 68mcg dose 3+. Patients receiving prior IO as anti-PD1/L1, anti-CTLA4 or combination were categorized into 3 groups: those who received IO <12 weeks (A); ≥12 but <52 weeks (B) and ≥52 weeks or no IO (C) prior to enrollment. Groups were compared for tumor shrinkage (TS), frequency who were alive (OS) at least 12 months and adverse events (AEs) including rash within 3 weeks of first dose of tebentafusp, hypo/hyperpigmentation events and cytokine release syndrome (CRS). Pre-treatment serum was analyzed for 11 inflammatory biomarkers.
Results
51 (44%) patients received prior IO within 12 weeks (A); 26 (22%) between 12-52 weeks (B) and 39 (34%) ≥52 weeks or never (C). The percentage patients with OS ≥12 months (A:63%, B:65%, C:56%) or TS (A:45%, B:50%, C:39%) were generally similar across groups. The occurrence of rash (A:84%, B:85%, C:85%), hypo/hyperpigmentation events (A:53%, B:62%, C:44%) and CRS (A:75%, B:73%, C:92%) were also similar between groups. Group A had the highest serum levels of T-cell related biomarkers (CXCL9, CXCL10, CXCL11, IL-10, TNFa); however, these biomarkers were not associated with clinical outcomes.
Conclusions
Tebentafusp recently demonstrated an OS benefit in 1L mUM against CPI. These new exploratory analyses suggest that in 2L+ mUM, clinical benefit and on-target AEs from tebentafusp were independent of prior CPI.
Clinical trial identification
NCT02570308.
Editorial acknowledgement
Legal entity responsible for the study
Immunocore.
Funding
Immunocore.
Disclosure
J.M. Piulats: Financial Interests, Institutional, Sponsor/Funding: Immunocore. T. Sato: Non-Financial Interests, Personal, Advisory Board: Immunocore; Non-Financial Interests, Personal, Advisory Board: Castle Biosciences; Financial Interests, Institutional, Sponsor/Funding: Immunocore; Financial Interests, Institutional, Sponsor/Funding: Verastem. J.J. Luke: Financial Interests, Institutional, Research Grant: Abbvie; Other, Personal, Other, Honoraria: Abbvie; Other, Personal, Other, Honoraria: Aligos; Other, Personal, Other, Honoraria: Array; Other, Personal, Other, Honoraria: Bayer; Other, Personal, Other, Honoraria and Travel Expenses: BMS; Other, Personal, Other, Honoraria: Checkmate; Other, Personal, Other, Honoraria: Cstone; Other, Personal, Other, Honoraria: Eisai; Other, Personal, Other, Honoraria: EMD Serono; Other, Personal, Other, Honoraria: KSQ; Financial Interests, Institutional, Research Grant: EMD Serono; Other, Personal, Other, Honoraria and Travel Expenses: Janssen; Other, Personal, Other, Honoraria: Merck; Financial Interests, Institutional, Research Grant: Merck; Other, Personal, Other, Honoraria and Travel Expenses: Mersana; Other, Personal, Other, Honoraria: Novartis; Other, Personal, Other, Honoraria: Partner; Other, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Advisory Board: Actym; Financial Interests, Personal, Stocks/Shares: Actym; Financial Interests, Personal, Advisory Board: Alphamab Oncology; Financial Interests, Personal, Advisory Role: Arch Oncology; Financial Interests, Personal, Stocks/Shares: Arch Oncology; Financial Interests, Personal, Advisory Board: Kanaph; Financial Interests, Personal, Stocks/Shares: Kanaph; Financial Interests, Personal, Advisory Board: Mavu; Financial Interests, Personal, Stocks/Shares: Mavu; Financial Interests, Personal, Advisory Board: Onc.AI; Financial Interests, Personal, Stocks/Shares: Onc.AI; Financial Interests, Personal, Advisory Board: Pyxis; Financial Interests, Personal, Stocks/Shares: Pyxis; Financial Interests, Personal, Advisory Board: Tempest; Financial Interests, Personal, Stocks/Shares: Tempest; Financial Interests, Institutional, Research Grant: Agios; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Corvus; Financial Interests, Institutional, Research Grant: Immatics; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Springbank; Financial Interests, Personal, Advisory Role: RefleXion; Financial Interests, Personal, Advisory Role: Regeneron; Financial Interests, Personal, Advisory Role: Ribon; Financial Interests, Personal, Advisory Role: Rubius; Financial Interests, Personal, Advisory Role: Silicon; Financial Interests, Personal, Advisory Role: Tesaro; Financial Interests, Personal, Advisory Role: Werewolf; Financial Interests, Personal, Advisory Role: Xilio; Financial Interests, Personal, Advisory Role: Xencor; Financial Interests, Institutional, Research Grant: Xencor; Financial Interests, Institutional, Research Grant: Kadmon; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: Tizona; Financial Interests, Personal, Other, Travel expenses: Pyxis. L. Collins: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. R. Edukulla: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. S.E. Abdullah: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. S. Leyvraz: Financial Interests, Personal, Advisory Role: Bayer.