Phase 3 Data Show Tebentafusp Provides Long-Term Survival Benefit in Patients With Metastatic Uveal Melanoma
The results confirm tebentafusp as a standard of care.
Data from the randomized phase 3 KIMMTRAK study (NCT03070392) show that tebentafusptebn (Kimmtrak; Immunocore) continues to provide long-term survival benefit in patients with previously untreated HLA-A*02:01-positive (+) 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
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The primary end point of the study was overall survival (OS), and secondary end points were overall response rate (ORR), progression-free survival (PFS), disease control rate (DCR), 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 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 estimated 3-year OS rate for tebentafusp was 27% (95% CI, 22%-33%) compared with 18% (95% CI, 11%-25%) for the control arm. Further, the median OS was 21.6 months in the tebentafusp group and 16.9 months in the control group.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 with HCA Healthcare at Leaders in Oncology Care, The Harley Street Clinic, and The Wellington Hospital in London, England, in an interview with Pharmacy Times.
In addition, 1-year and 2-year PFS rates and DCRs for the tebentafusp group were higher (17% and 8%, respectively) than the control group (9% and 3%, respectively). Further, the DCR was 46% in the tebentafusp group and 27% in the control group. Approximately one-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 with tebentafusp 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 [have] HLA*A2.01+ [disease] 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 proved 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 tumor,” said Nathan. “An academic study, TebeMRD [NCT05315258], is underway.”
References
1. Immunocore presents three-year overall survival data from the KIMMTRAK phase 3 trial. News release. Immunocore. 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. Hassel JC, Piperno-Neumann S, Rutkowski P, et al. Three-year overall survival with tebentafusp in metastatic uveal melanoma. Published online October 21, 2023. N Engl J Med. doi:10.1056/NEJMoa2304753
