Dose-seeking Study of Pembrolizumab Plus Vemurafenib and Cobimetinib Advanced Melanoma
Status:
Active, not recruiting
Trial end date:
2024-05-01
Target enrollment:
Participant gender:
Summary
The study plans to treat patients with pembrolizumab and thus blocking the PD-1/PD-L1 axis
would render tumor-infiltrating lymphocytes (TILs) in the tumor parenchyma more functional as
a consequence of BRAF inhibition, such that T cell activation by BRAFi would not be dampened
by the PD-1/PD-L1 interaction. This combination would reverse dysfunction among T cells in
the tumor parenchyma, maximizing T cell mediated immune anti-tumor efficacy. Progression free
survival (PFS) with pembrolizumab in KEYNOTE-001 was 57% at 6 months, and 46.4% in the more
recently reported phase III trial. PFS with vemurafenib treatment in BRIM-3 was ~50% at 6
months. Combined treatment with pembrolizumab, cobimetinib and vemurafenib for BRAF mutant
melanoma is hypothesized to be safe and to improve the PFS compared to these recent
historical controls. Because this combination has not yet been tested, and because the
primary objective is to assess safety, the investigators are staging accrual in the first
phase of the trial. The study aims to accrue up to 30 patients to the mTPI design of this
study with the expectation that there will be at least 30 patients treated at RP2D. In case
there are less than 30 patients on the RP2D, additional patients will be accrued. Patients
will continue to receive treatment with pembrolizumab, vemurafenib and cobimetinib until
disease progression or dose limiting toxicity. Patients with treatment response and no dose
limiting toxicity may receive treatment with pembrolizumab for up to 24 months.