Does tebentafusp provide survival benefit in patients with advanced uveal melanoma?

The study aimed to investigate the safety and effectiveness of immunotherapy drug tebentafusp in previously untreated advanced uveal melanoma. The study showed that tebentafusp is effective and improved the overall survival in patients with uveal melanoma.

Melanoma is an aggressive kind of skin cancer. Uveal melanoma accounts for up to 5% of all melanoma cancer and begins in the colored cells of the eye. Up to 50% of patients with uveal melanoma experience metastasis (cancer spread) mostly in the liver. The molecular mechanism of uveal melanoma is different from common skin melanoma. Therefore, the treatment response with common immune checkpoint inhibitors (ICI) such as pembrolizumab (PEM; Keytruda) and ipilimumab (IPI; Yervoy) are not so successful with uveal melanoma.

Tebentafusp is a fusion protein that recognizes two targets at the same time. One targets the melanoma cells and the other targets immune cells. Therefore, it can make a connection between these two cell types. This function allows the immune cells to immediately attack and kill the melanoma cells. The safety and effectiveness of tebentafusp compared to current standard melanoma therapies in advanced uveal melanoma are under investigation.

The study involved a total of 378 previously untreated patients with advanced uveal melanoma. They were randomly assigned to two groups. 252 patients received tebentafusp (group 1) and 126 patients received standard melanoma therapies (group 2) such as PEM (103) or IPI (16) or dacarbazine (DTIC; 7). The average duration of follow-up was 14.1 months.

The overall survival in group 1 patients was significantly longer (21.7 months) compared to group 2 (16 months). After 1 year, significantly more patients in group 1 were alive (73%) compared to group 2 (59%). Tebendafusp was associated with a 49% higher chance of survival compared to control therapies. 

After 6 months, significantly more patients in group 1 were alive without cancer worsening (31%) compared to group 2 (19%). Tebentafusp was associated with a 27% lower risk of cancer progression compared to control therapies. Significantly more patients in group 1 had disease control (46%) compared to group 2 (27%). Disease control is when the tumor shrinks or stops progressing. 

The most common treatment-related side effects in group 1 were related to a release of immune cells in the bloodstream. These included fever (76%), chills (47%), and low blood pressure (38%). Severe side effects were reported in 44% of group 1 and 17% of group 2.

This study showed that treatment with tebentafusp in patients with advanced uveal melanoma was well tolerated and was associated with longer overall survival compared to patients treated with current standard therapies. 

This study was supported by Immunocore, the manufacturer of tebentafusp. Tebentafusp is awaiting approval from the European and US Medication agencies.