Dr Nathan on the Design of the IMCgp100-202 Trial in Uveal Melanoma

Paul D. Nathan, MBBS, PhD, FRCP, consultant medical oncologist, Mount Vernon Cancer Centre, discusses the design of the phase 3 IMCgp100-202 trial (NCT03070392) of tebentafusp-tebn (Kimmtrak) in patients with previously untreated, HLA-A*02:01–positive metastatic uveal melanoma, highlighting the key enrollment criteria of the randomized, open-label study.

Notably, the IMCgp100-202 study randomly assigned patients with metastatic uveal melanoma to receive tebentafusp vs the investigator's choice of pembrolizumab (Keytruda), ipilimumab (Yervoy) or dacarbazine. This trial produced data that supported the FDA approval of tebentafusp in this patient population.

Because of the significant clinical demand in uveal melanoma, the control arm was designed as an investigator’s choice arm, indicating the absence of an established standard of care prior to the approval of tebentafusp, Nathan states. In the control arm, patients had the option to receive pembrolizumab, ipilimumab, or dacarbazine chemotherapy, with 82% opting for pembrolizumab, Nathan notes. Patients were randomly assigned in a 2:1 ratio to either tebentafusp or a control agent, he adds.

To be eligible for the trial, patients needed to have HLA-A*02:01–positive disease or an HLA-A*02:01 haplotype. The presence of HLA-A*02:01 is crucial for the drug's mechanism of action because tebentafusp requires HLA to bind to tumor cells, he expands. This study focused on first-line treatment, and patients had to exhibit a good ECOG performance status, Nathan notes. Included were patients with first-line, metastatic uveal melanoma who had measurable, HLA A*02:01–positive disease, he emphasizes. 

The characteristics of the patient population in the study accurately represented the characteristics of real-world patients with metastatic uveal melanoma, he continues. Nathan says that a notable distinction between uveal melanoma and cutaneous melanoma lies in the hepatotropism of uveal melanoma. Most patients with metastatic uveal melanoma enrolled in the trial had hepatic disease, either exclusively in the liver or in combination with extrahepatic sites, he explains. It is essential to highlight that the characteristics of the registrational study's population mirrored the characteristics of patients encountered in clinical settings, with only a small fraction (4%) having solely extrahepatic disease, Nathan shares. The predominant clinical need was in patients with hepatic involvement, he concludes.