Phase 3 Study Results Show Tebentafusp Provides Long-Term Survival Benefit in Patients With Metastatic Uveal Melanoma

Data from the randomized phase 3 KIMMTRAK study (NCT03070392) show that tebentafusp-tebn (Kimmtrak; Immunocore) continues to provide long-term survival benefit in patients with previously untreated HLA-A*02:01+ metastatic uveal melanoma (mUM). Tebentafusp is a bispecific (gp100 x CD3) immune mobilizing monoclonal T-cell receptor against cancer that is approved for treatment in adults with previously untreated HLA-A*02:01+ mUM.¹

Image credit: Evgeniy Kalinovskiy | stock.adobe.com

The primary endpoint of the study was OS, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), disease control rate, and safety, and an exploratory endpoint was circulating tumor DNA (ctDNA) reduction. Patients were randomly assigned to receive tebentafusp or investigator’s choice (IC) of pembrolizumab (Keytruda; Merck), ipilimumab (Yervoy; Bristol-Myers Squibb), or dacarbazine (control arm). Among the total 378 enrolled patients, 252 received tebentafusp and the remaining 126 patients received pembrolizumab (n = 103), ipilimumab (n = 16), or dacarbazine (n = 7).²

After a minimum follow-up of 36 months, the 3-year landmark OS of tebentafusp was 27% (95% CI, 22%-33%) compared to 18% (95% CI, 11%-25%) for the control arm, with a median OS of 21.6 months and 16.9 months, respectively.²

“These results confirm that the significant benefit conferred by tebentafusp is durable and maintained at the 3-year landmark. They allow clinicians and patients to discuss the possibility of longer-term benefit with tebentafusp treatment,” said primary investigator Paul Nathan, PhD, FRCP, a consultant medical oncologist at Mount Vernon Cancer Centre, United Kingdom, in an interview with Pharmacy Times.

In addition, 1-year and 2-year PFS rates and DCR rates for the tebentafusp group were higher (17% and 8%, respectively) than the control group (9% and 3%, respectively). Further, the disease control rate was 46% in the tebentafusp groiup and 27% in the control group. Approximately a third of patients who received tebentafusp treatment continued to see a response at 18 months. Further, the trial evaluated ctDNA clearance as a predictor of OS, and ctDNA clearance on tebentadusp occurred in 37% of patients, and was associated with longer OS.^1,2

“These results confirm tebentafusp as a standard of care for patients who are HLA A2.01+ with previously untreated mUM and give confidence regarding longer term benefits in this poor prognosis disease, [and also] confirm the durability of benefit with the first T-cell receptor bispecific molecule proven to improve OS,” said Nathan.

The rate of treatment discontinuation as a result of related AEs continued to be lower in the tebentafusp arm (2%) than the control arm (5%). No new safety signals were identified and there were no deaths related to treatment.^1,2

“Next steps will involve investigating the activity of tebentafusp in patients with residual microscopic disease following treatment of their primary tumour,” said Nathan. “An academic study, TebeMRD [NCT05315258], is underway.”

Reference

1. Immunocore. Immunocore presents three-year overall survival data from the KIMMTRAK Phase 3 trial. News release. October 21, 2023. Accessed October 24, 2023. https://ir.immunocore.com/news-releases/news-release-details/immunocore-presents-three-year-overall-survival-data-kimmtrak

2. Piperno-Neumann, S, Hassel J, Baurain JF, et al. Three-survival with tebentafusp in previously untreated metastatic uveal melanoma in a phase 3 trial. ClinicalTrials.gov: NCT03070392. Accessed October 24, 2023. https://clinicaltrials.gov/study/NCT03070392