Multiple studies have been developed to improve upon prior results, and are summarized in Table 4. These include systemic ICIs in combination with agents such as VEGF inhibitors lenvatinib (KEYMAKER-U02D, NCT04700072) and bevacizumab (NCT04356729), novel glutamate modulator troriluzole (NCT04899921), and tumor treating fields (TTF) devices such as NovoTTF-100A (NCT04129515) or Sonocloud (SONIMEL01, NCT04021420).
Beyond the systemic administration of ICIs, IT approaches using various immunotherapies are currently being investigated in melanoma. IT IL-2 was first assessed in patients with melanoma patients with LMD. While response rates were low and the associated toxicities significant, a subset of melanoma patients with LMD treated with IT IL-2 achieved durable long-term survival with 1-, 2- and 5-year OS rates of 36%, 26%, and 13%. An ongoing study (NCT03025256) is evaluating combined systemic and IT nivolumab in this patient population.
As noted earlier, compelling data suggests synergies between PD-1 or CTLA-4 targeting ICIs and RT for the treatment of MBM, supported by data from retrospective series. These have led to a plethora of studies evaluating SRS combined with either single agent anti-PD-1 (NCT02716948, NCT02978404, and NCT02858869) or PD-1/CTLA-4 doublet (NCT03340129) in MBM.
Other studies are evaluating novel small molecules including the class I selective oral HDAC inhibitor HBI-8000 (NCT04674683) and STAT3 inhibitor WP1066 (NCT01904123).
Chin Clin Oncol. 2022;11(3):24 © 2022 AME Publishing Company