Dose-seeking and efficacy study of combination BRAFi and high-dose IFN (HDI) for therapy of advanced melanoma.

TPS9110 Background: New immunotherapies and BRAF inhibitors (BRAFi) have improved the prognosis of advanced melanoma. Although BRAFi induce regression in ~50% of patients (pts), responses are incomplete and progression typically occurs at 6 months. Intrinsic/acquired resistance mechanisms represent limitations to single agent BRAFi use. Conversely, immunotherapies benefit only 18-30% of patients. In vitro and in vivo studies suggest that treating BRAF mutated melanoma cells with BRAFi increases sensitivity to IFN. We planned a dose-selection and dose-expansion study to evaluate the novel sequential combination of BRAFi followed after 2 weeks by concurrent BRAFi/IFNα. Methods: Study will enroll pts with BRAF V600E recurrent/inoperable stage III/IV melanoma. Primary objectives are to evaluate safety/toxicity, identify a phase II dose (RP2D) of combination, and improve progression free survival (PFS). Secondary objectives include improving response rates and documenting evidence of immune modulation. Pts wil...