72P - Concurrent local therapy (CLT) extends clinical benefit of tebentafusp (tebe) in metastatic uveal melanoma (mUM) patients (pts)

Background

Tebe is a bispecific fusion protein that binds gp100 presented by HLA-A*02:01 on melanoma cells and engages CD3 T-cells. While tebe has significantly improved overall survival in HLA-A*02:01+ mUM pts, clinical benefit after disease progression is limited. Here, we examine the efficacy and safety of adding CLT to tebe upon radiological progression with tebe alone.

Methods

In this multicenter retrospective study, mUM pts treated with tebe and CLT were included. CLT consisted of liver-directed therapies (LDT) and extrahepatic soft tissue irradiation. Efficacy was assessed before and after CLT per RECIST version 1.1. PFS with tebe alone (PFS1) was compared to that after adding CLT to tebe upon progression (PFS2) in the same patients. Treatment-related adverse events (trAEs) were graded per CTCAE version 5.0.

Results

30 pts were included [(50% male, median age at diagnosis of 56 years (range, 13-78)]. Pts had a median of 0 lines of systemic therapy (range, 0-4) or CLT (range, 0-12) prior to tebe. 12 pts (40%) had prior immunotherapy. Of the 30 pts, 21 (70%) received concurrent LDT, 7 (23%) had extrahepatic irradiation, and 2 (7%) had both. For tebe alone, the ORR was 12% (95% CI, 4-30). After adding CLTs, the ORR was 30% (95% CI, 17-47), including 2 complete responses with LDT. The disease-control rate with tebe alone was 40% (95% CI, 23-59) versus 64% (95% CI, 47-78) after CLT. Median PFS1 was 5.2 months (mos) (95% CI, 2.7-15.4), while median PFS2 was 14.8 mos (95% CI, 9.2-NA). The stratified hazard ratio for progression was 0.42 (95% CI, 0.23-0.80; p = 0.008). CLT also allowed treatment beyond progression for a median of 5.6 mos (range, 1.5-22). 4 pts had ctDNA levels available pre- and post-CLT. 2 pts (50%) had decreased ctDNA with tebe alone, while all 4 (100%) had decreased ctDNA after LDT. Tebe with CLT was well-tolerated with a rate of grade ≥3 trAEs of 21% and no treatment discontinuation due to trAEs.

Conclusions

CLT with tebe was well-tolerated and appears to augment treatment benefit and extend the duration of clinical benefit with tebe in mUM pts. This merits further studies to assess the clinical utility of tebe and CLT.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

K. Montazeri: Financial Interests, Personal, Advisory Board: Immunocore. A.N. Shoushtari: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Immunocore, Novartis, Erasca; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Immunocore, Pfizer, Novartis, Checkmate Pharmaceuticals, Linnaeus Therapeutics, Foghorn Therapeutics, Prelude Therapeutics, Iovance Biotherapeutics, Obsidian Therapeutics; Financial Interests, Institutional, Coordinating PI: Polaris, Xcovery, Targovax ASA; Non-Financial Interests, Personal, Member: ASCO. M. Orloff: Financial Interests, Personal, Invited Speaker: Immunocore; Financial Interests, Personal, Advisory Board: Replimune, Ideaya, Delcath, Immunocore; Financial Interests, Institutional, Local PI: Immunocore, Ideaya, Ascentage, Foghorn, Iovance, Linnaeus, Trisalus. T. Sato: Financial Interests, Personal, Advisory Board: Immunocore, Castle Biosciences. S. Khan: Financial Interests, Personal, Advisory Board: Castle Biosciences, Replimune Inc. R.D. Carvajal: Financial Interests, Personal, Speaker, Consultant, Advisor: Castle Biosciences, Delcath, Ideaya, Immunocore, Trisalus. I. Mehmi: Financial Interests, Personal, Invited Speaker: Immunocore, BMS; Financial Interests, Personal, Stocks/Shares: Delcath, Immunocore, Ideaya, In8Bio, Iovance. O. Hamid: Financial Interests, Personal, Advisory Board: Alkermes, Amgen, BMS, Bactonix, Beigene, Bioatla, Eisai, GSK, Georgiamune, GigaGen, Grit Bio, IO Biotech, Idera, Immunocore, Incyte, Instil Bio, Iovance, Janssen, KSQ, Merck, 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, Local PI: Aduro, Akeso, Amgen, Arcus, BMS, Bioatla, CytomX, Exelixis, GSK, Idera, Immunocore, Incyte, Iovance, Merck, Merck Serono, Moderna, Nextcure, Novartis, Pfizer, Roche Genentech, Seagen, Sanofi/Regeneron, Torque, Zelluna. R. Sullivan: Financial Interests, Personal, Advisory Board, Advisory board/consultancy: MSD; Financial Interests, Personal, Other, Consultant: Marengo; Financial Interests, Personal, Advisory Board, Consultancy/SAB: Novartis; Financial Interests, Personal, Other, Consultancy: Pfizer, Replimune; Financial Interests, Personal, Royalties: Up-to-Date; Financial Interests, Institutional, Coordinating PI, Phase 1 trial PI: Marengo; Financial Interests, Institutional, Local PI: Novartis, Synthekine, Immunocore, Springworks; Financial Interests, Institutional, Coordinating PI: Mural, Moderna; Financial Interests, Institutional, Steering Committee Member: Merck. All other authors have declared no conflicts of interest.