Highlights on melanoma/skin cancer 2

Dr Iris Dirven, a medical oncologist in training at the University Hospital of Brussels discussed her selection from the rapid oral abstract session on melanoma/skin cancer.

The NADOM trial investigated the use of targeted therapy with darovasertib in the neoadjuvant setting for uveal melanoma. The goal was to reduce the need for enucleation in patients with primary uveal melanoma. The results demonstrated a significant response to neoadjuvant treatment, evidenced by reductions in tumour height and volume, as well as a decreased need for enucleation. Ongoing research aims to determine if this treatment can contribute to eye-sparing procedures. Additionally, a phase 3 study is ongoing in patients with metastatic uveal melanoma.

The KEYNOTE-942 study investigated individualized neoantigen therapy using an mRNA vaccine combined with pembrolizumab. A three-year update on RFS was presented, showing a significant improvement with the combined treatment compared to pembrolizumab alone. With a hazard ratio of 0.5, the risk of recurrence was reduced for both RFS and DMFS. The results of ongoing phase 3 trials are eagerly awaited to determine if this treatment will become the new standard of care for adjuvant therapy.

The phase 2 De-Squamate study evaluated the administration of four cycles of neoadjuvant pembrolizumab in patients with locally advanced resectable cutaneous SCC. The aim was to reduce the need for surgery and postoperative therapy, which often have significant cosmetic and physical side effects. The results were impressive, with 63% of patients achieving a combined rate of clinical complete response or pathological complete response. In nearly half of the patients, this treatment reduced the need for surgery and postoperative radiotherapy. Given the safety profile of pembrolizumab, this therapy is expected to be practice-changing.

The OBX-115 study investigates engineered TIL cell therapy in patients with unresectable or metastatic melanoma resistant to immune checkpoint inhibitors. This approach enables the regulatable expression of membrane-bound IL-15 via acetazolamide, eliminating the need for concurrent IL-2 administration and reducing severe adverse events. This phase 1 trial focused on safety, tolerability, and identifying the recommended dose, with all patients pretreated with anti-CTLA-4 and anti-PD1. Results showed that half of the patients responded to the treatment, while the other half had stable disease. These first human results demonstrate impressive response and disease control rates in this heavily pretreated population, which currently lacks a standard of care option.