Evaluating the safety and effectiveness of tebentafusp in previously treated patients with advanced uveal melanoma

The study evaluated the safety and effectiveness of tebentafusp (Kimmtrak) in patients with metastatic uveal melanoma who had received previous treatments. The study found that tebentafusp had promising effectiveness and a good safety profile in these patients.

Uveal melanoma is a rare and aggressive eye tumor. Up to half of the patients have cancer spread to other parts of the body. Currently, there is no standard treatment for metastatic uveal melanoma. The main treatments used are surgery (including removal of the eye) and radiation therapy. Previous research showed that only 37% of patients survived after 1 year in previously treated metastatic uveal melanoma patients.

Immunotherapy has become an important part of treatment in many cancers, including melanoma. Tebentafusp is an immunotherapy drug called a bispecific fusion protein. It works by getting close enough to the cancer cells to attack them. When compared to other immunotherapy drugs, tebentafusp proved a better survival time for patients with uveal melanoma. However, how the tumor responds to tebentafusp influences the outcomes of the patients is still under investigation. 

The study included 127 patients with metastatic uveal melanoma. Each patient had at least one type of treatment before the study. Most of the patients had cancer spread to the liver. Patients received tebentafusp intravenously weekly for 4 weeks. Response Evaluation Criteria in Solid Tumors (RECIST) is a method used to evaluate the response of a tumor to a new treatment. Patients who had progressive disease based on RECIST could continue the treatment. The average treatment duration was 5.5 months. The average follow-up period of patients was 19.5 months.

Based on RECIST criteria, the study drug showed a low response rate of 5%. The average response duration was 8.7 months. The average time to obtain a treatment response was 4.6 months. 45% of patients had stable disease (the tumor did not grow or spread) after at least 8 weeks. The overall disease control rate was 32% after 16 weeks and 23% after 24 weeks. Tumor shrinkage was observed in 44% of patients. 

After 1 year, 62% of patients were alive. The average overall survival was 16.8 months. 86% of the patients who had any tumor shrinkage (not only by RECIST criteria) were alive after 1 year. 

Also, early detection of a reduction in circulating tumor DNA (ctDNA) was strongly associated with better chances of survival, even in patients with progressive disease. 

All patients reported at least one treatment-related side effect. The most common side effects included skin rash (87%), fever (80%), itchiness (67%), and chills (64%). 40% of patients had severe side effects. Most of these were skin reactions. 

The study concluded that tebentafusp is safe and has promising effectiveness in previously treated patients with metastatic uveal melanoma.

This study did not have a comparison group. The study was funded by Immunocore Ltd., the manufacturer of tebentafusp.