Dr Weiss on the Ongoing Investigation of Tebentafusp With or Without Pembrolizumab in Non-Uveal Melanoma

Sarah Weiss, MD, medical oncologist, director, Melanoma/Cutaneous Oncology Program, Rutgers Cancer Institute, associate professor, Division of Medical Oncology, Robert Wood Johnson Barnabas Health, discusses the ongoing phase 2/3 TEBE-AM trial (NCT05549297) of tebentafusp-tebn (Kimmtrak) with or without pembrolizumab (Keytruda) in a subset of pretreated patients with non-uveal melanoma.

Tebentafusp monotherapy gained FDA approval in January 2022 for the treatment of HLA-A*02:01–positive adult patients with unresectable or metastatic uveal melanoma, based on the results of the phase 3 IMCgp100-202 trial (NCT03070392). The agent has also demonstrated benefit in non-uveal melanoma when administered early in the treatment course. However, its efficacy and safety in combination with a PD-1 inhibitor has not yet been determined in non-uveal melanoma.

Based on this need, a multicenter study was designed to compare the use of single-agent tebentafusp vs tebentafusp plus pembrolizumab or investigator's choice of subsequent therapy, Weiss begins. The trial will enrolled patients who have HLA-A*02:01–positive non-uveal melanoma and have previously progressed on or within 6 months of the last dose of an anti–PD-1 or –PD-L1agent, received ipilimumab (Yervoy), and received a BRAF/MEK inhibitor regimen if the patient harbors an actionable BRAF mutation. Patients will be randomly assigned 1:1:1 to receive tebentafusp monotherapy (arm A), tebentafusp plus pembrolizumab (arm B), or proceed straight to efficacy follow-up (arm C), Weiss details.

Those in arm C will receive investigator's choice of salvage chemotherapy, retreatment, investigational agents in a clinical trial setting, or best supportive care, she adds. This allows for a comparison between tebentafusp-containing regimens and standard real-world treatment options, Weiss explains. 

Patients in the phase 2 portion will be stratified by lactate dehydrogenase (LDH)status, while those who proceed to the phase 3 portion will be stratified by both LDH and BRAF-mutation status. Randomization to the phase 3 portion will begin after phase 2 accrual is competed. The primary objectives of this study include circulating tumor DNA reduction relative to baseline in the phase 2 portion, and overall survival in both phases. The phase 2 portion is currently enrolling patients.