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Regular and Young Investigator Award Abstracts
Clinical Trials In Progress
538 Updated survival of patients with previously treated metastatic uveal melanoma who received tebentafusp
Free
  1. Joseph Sacco1,
  2. Richard Carvajal2,
  3. Marcus Butler3,
  4. Alexander Shoushtari4,
  5. Jessica Hassel5,
  6. Alexandra Ikeguchi6,
  7. Leonel Hernandez-Aya7,
  8. Paul Nathan8,
  9. Omid Hamid9,
  10. Josep Piulats10,
  11. Matthew Rioth11,
  12. Douglas Johnson12,
  13. Jason Luke13,
  14. Enrique Espinosa14,
  15. Serge Leyvraz15,
  16. Chris Holland16,
  17. Michelle McCully16,
  18. Shaad Abdullah16 and
  19. Takami Sato17
  1. 1The Clatterbridge Cancer Centre, Wirral, UK
  2. 2Columbia University Medical Center, New York, USA
  3. 3Princess Margaret Cancer Centre, Toronto, Canada
  4. 4Memorial Sloan-Kettering Hospital, New York, NY, USA
  5. 5University Hospital Heidelberg, Heidelberg, Germany
  6. 6Stephenson Cancer Center, University of Oklahoma, Oklahoma City, USA
  7. 7Washington University School of Medicine, St. Louis, USA
  8. 8Mount Vernon Hospital, Northwood, UK
  9. 9The Angeles Clinic and Research Institute, Los Angeles, CA, USA
  10. 10Institut Català d’Oncologia, Barcelona, Spain
  11. 11University of Colorado Cancer Center, Colorado, USA
  12. 12Vanderbilt-Ingram Cancer Center, Nashville, TN, USA
  13. 13UPMC Hillman Cancer Center, Pittsburgh, PA, USA
  14. 14Hospital Universitario La Paz, Madrid, Spain
  15. 15Charité Comprehensive Cancer Center, Berlin, Germany
  16. 16Immunocore, Rockville, USA
  17. 17Sidney Kimmel Cancer Center, Philadelphia, PA, USA

Abstract

Background Tebentafusp, a bispecific fusion protein consisting of an affinity-enhanced T cell receptor fused to an anti-CD3 effector that can redirect T cells to target gp100+ cells, has shown an overall survival benefit for patients with untreated metastatic uveal melanoma (mUM) in a Ph3 trial (NCT03070392). Metastatic uveal melanoma (mUM) is a historically treatment-refractory tumor with 1-year (yr), 2-yr and 3-yr OS rates of 37%, 15% and 9%, respectively, and median OS of 7.8 months in 2L+ patients.1 In the primary analysis of the phase 2 IMCgp100–102 study (NCT02570308) enrolling patients with previously treated mUM, the 1-year overall survival (OS) rate was 62% with median OS of 16.8 months.2 We present updated OS and safety after 2-year follow-up.

Methods 127 HLA-A*02:01+ 2L+ mUM patients were dosed weekly with tebentafusp following intra-patient dose escalation: 20mcg dose 1, 30mcg dose 2 and 68mcg dose 3+. Primary objective was ORR and secondary objectives included safety, OS and PFS. Here we present the updated OS and safety (data cut-off 31 Mar 2021).

Results Median follow-up was 29.9 mos (range 1.8 – 59.9 mos). With extended follow-up, the 1-yr, 2-yr and 3-yr OS rates were 61%, 37% and 24%, respectively (figure 1). Median OS remained unchanged at 16.8 mos (95% CI, 12.8 – 22.5 mos).Mean and median duration of treatment were 9.5 mos and 5.6 mos (0 – 47.4 mos), respectively. As previously reported, most treatment-related AEs (TRAEs) occurred early on treatment. Beyond 6 months, no TRAE led to treatment discontinuation. No new safety signals, changes in the type or treatment-related deaths were reported. Beyond 12 months, there were a total of 7 Grade (G) 3 or 4 events in 3 (7%) patients, all were temporally related to tumor progression and majority included lab abnormalities. Episodes of rash, a common tebentafusp-related AE early on-treatment, were infrequent after 6 months, with no Grade 3 or 4 events.

Abstract 538 Figure 1
Abstract 538 Figure 1

Kaplan-Meier estimate of overall survival at 2-yr follow-up of IMCgp100-102

Conclusions This study provides the longest follow-up of OS and safety of a soluble TCR therapeutic to date. Tebentafusp continued to show promising survival for 2L+ mUM patients with estimated 2-yr OS rate of 37%. Tebentafusp’s safety profile was as expected and consistent with primary analysis showing that most adverse events occur early on treatment with incidence and severity decreasing with prolonged exposure.

Trial Registration NCT02570308

References

  1. Rantala ES, Hernberg M, Kivela TT. Overall survival after treatment for metastatic uveal melanoma: a systematic review and meta-analysis. Melanoma Res 2019;29:561–568.

  2. Sacco JJ, Carvajal R, Butler MO, et al. A phase (ph) II, multi-center study of the safety and efficacy of tebentafusp (tebe) (IMCgp100) in patients (pts) with metastatic uveal melanoma (mUM). Ann Oncol 2020;31: S1442–S1143.

Ethics Approval The institutional review board or independent ethics committee at each center approved the trial. The trial was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines.

https://doi.org/10.1136/jitc-2021-SITC2021.538

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