Oral Presentation Australasian Melanoma Conference 2026

Five-year survival with tebentafusp in previously untreated metastatic uveal melanoma in a phase 3 trial (#73)

Paul Nathan 1 2 , Sophie Sophie Piperno-Neumann 3 , Jessica C Hassel 4 , Marcus O Butler 5 6 , Max Schlaak 7 , Ryan J Sullivan 8 , Reinhard Dummer 9 , John M Kirkwood 10 , Joseph J Sacco 11 12 , Alexander N Shoushtari 13 14 , Josep M Piulats 15 16 , April KS Salama 17 , Marlana M Orloff 18 , Anthony M Joshua 19 , Sebastian Ochsenreither 7 , Lauris Gastaud 20 , Brendan D Curti 21 , Lev V Demidov 22 , Mohammed M Milherm 23 , Bartosz Chmielowski 24 , Kari L Kendra 25 , Paolo A Ascierto 26 27 , Eric H Bernicker 28 , Richard D Carvajal 29 30 , Omid A Hamid 31 , Laura Collins 32 , Sarah Lockwood 33 , Jaymin M Patel 34 , Jean-Francois Baurain 35 , Piotr Rutkowski 36 , Mark Shackleton 37
  1. Mount Vernon Cancer Centre, Northwood, UK
  2. University College London, London, UK
  3. Institut Curie, PSL Research University, Paris, France
  4. Heidelberg University, Medical Faculty Heidelberg, Department of Dermatology and National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital Heidelberg, Heidelberg, Germany
  5. Princess Margaret Cancer Centre, Department of Medical Oncology and Hematology, Toronto, ON, Canada
  6. Departments of Medicine and Immunology, University of Toronto, Toronto, ON, Canada
  7. Charité -Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Department of Dermatology, Venereology and Allergology, Berlin, Germany
  8. Massachusetts General Brigham Cancer Institute, Boston, MA
  9. University of Zürich Hospital, Zürich, Switzerland
  10. University of Pittsburgh Medical Center UPMC Cancer Center, Pittsburgh, PA
  11. Clatterbridge Cancer Center - NHS Foundation Trust, Wirral, United Kingdom
  12. University of Liverpool, Liverpool, UK
  13. Memorial Sloan Kettering Cancer Center, New York, NY
  14. Weill Cornell Medical College, New York, NY, USA
  15. Institut Català d'Oncologia, Barcelona, Spain
  16. IDIBELL Institut d'Investigació Biomèdica de Bellvitge, Barcelona, Spain
  17. Duke University, Durham, NC
  18. Sidney Kimmel Cancer Center, Jefferson University, Philadelphia, PA
  19. Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, Darlinghurst, NSW, Australia
  20. Centre Antoine Lacassagne, Nice, France
  21. Providence Portland Medical Center, Portland, OR
  22. N.N. Blokhin National Medical Research Center of Oncology, Moscow, Russian Federation
  23. University of Iowa Hospitals and Clinics, Iowa City, IA
  24. University of California Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA
  25. The James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus, OH
  26. Università degli Studi di Napoli Federico II, Napoli, Italy
  27. Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Italy
  28. Neal Cancer Center, Houston Methodist Hospital, Houston, TX
  29. Northwell Health Cancer Institute, New Hyde Park, NY, USA
  30. Cold Spring Harbor Laboratory Cancer Center, Cold Spring Harbor, NY, USA
  31. The Angeles Clinic and Research Institute, a Cedars-Sinai Affiliate, Los Angeles, CA
  32. Immunocore Ltd, Abingdon, United Kingdom
  33. Pivotal Statistics Ltd, Macclesfield, United Kingdom
  34. Immunocore LLC, Conshohocken, USA
  35. Cliniques Universitaires Saint-Luc, UC Louvain, Brussels, Belgium
  36. Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
  37. Monash University, Melbourne, VIC, Australia

Background: Metastatic uveal melanoma (mUM) has a very poor prognosis with a historical survival rate of <10% at 5 yrs. Tebentafusp, a first in class ImmTAC bispecific (gp100 x CD3), is approved for adult HLA-A*02:01+ patients with unresectable or mUM based on a phase 3 study demonstrating improved overall survival (OS) compared to investigator’s choice (IC) (HR 0.51; IMCgp100-202; NCT03070392). This benefit was maintained at the 3-yr follow-up (HR 0.68), with a 3-yr OS rate of 27% for tebentafusp and 18% for IC. Molecular response assessed by ctDNA reduction was a better indicator of OS benefit than traditional RECISTv1.1 measurements. Here we report updated analyses of OS after a minimum follow-up of 5 yrs.

Methods: In this randomized, open-label, Phase 3 trial, first line HLA-A*02:01+ mUM patients were randomized 2:1 to receive tebentafusp or IC of single-agent pembrolizumab, ipilimumab or dacarbazine, stratified by lactate dehydrogenase. Primary endpoint was OS. ctDNA reduction was an exploratory endpoint. OS was estimated using Kaplan-Meier methods and treatment effects compared using Cox proportional hazards model. A Cox model, adjusted for baseline and time-varying covariates at progression, compared post-progression survival in tebentafusp patients with versus without treatment beyond radiographic progression (TBP).

Results: 378 patients were randomized to tebentafusp (252) or IC (126; 82% pembrolizumab). With extended follow-up, the OS continued to favor tebentafusp, with a stratified hazard ratio of 0.67 (95% CI, 0.54-0.85). The 5-year OS rate for tebentafusp was 16% (95% CI, 11-21) vs 8% (95% CI, 4-14) for IC. The OS benefit was evident even in patients with known poor prognostic factors, including those with large tumors ≥ 10 cm.

OS benefit was also seen in patients who did not have radiographic response including those with best response of progressive disease (PD) or those with a best change of tumor growth (>20%). Notably, in the tebentafusp arm, TBP was associated with better OS compared to no TBP, even after adjusting for covariates (HR 0.61; 95% CI, 0.44-0.83).

In tebentafusp-treated patients, longer OS was associated with undetectable ctDNA at baseline or ctDNA reductions ≥50% by week 9.