Study of PX-866 and Vemurafenib in Patients With Advanced Melanoma

Inclusion Criteria

• •≥ 18 years at time of consent
• •If a sexually active male or a sexually active female of child-bearing potential, agrees to use a highly effective form of contraception (including birth control pills, barrier device, or intrauterine device)from the time of consent 90 days following the last dose of study drug
• •If female of child-bearing potential, negative pregnancy test
• •For Phase 1: must have histologically or cytologically-confirmed advanced cancer that is BRAF mutation-positive (V600E or V600K) for which there is no remaining standard therapy with curative potential. Patients must have disease sites amenable to biopsy. For Phase 2: must have histologically or cytologically-confirmed BRAF mutation-positive (V600E or V600K) advanced (defined as unresectable Stage IIIC or IV) melanoma that has not been treated with a selective BRAF inhibitor
• •For Phase 1: must have measurable or non-measurable disease. For Phase 2: must have measurable disease per RECIST 1.1
• •For Phase 1: no restriction on number of prior therapy regimens. For Phase 2: the following restrictions on prior therapy apply: 1) must not have been treated with a selective BRAF inhibitor and must not have had more than 2 prior treatment regimens for advanced metastatic disease; 2) must have completed prior cytotoxic chemotherapy a minimum of 4 weeks prior to starting PX-866 and/or vemurafenib (except for BCNU and/or mitomycin C, which must have been completed a minimum of 6 weeks prior to starting therapy). Prior biologic therapy and localized radiation therapy must have been completed a minimum of 2 weeks prior to starting therapy.
• •All toxicities related to prior cancer therapies other than alopecia must have resolved to Grade 1 or less
• •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• •In the opinion of the clinical investigator, life expectancy \> 3 months
• •Adequate hematologic function
• •Adequate hepatic function
• •Serum creatinine \< 2.0 mg/dL
• •Adequate cardiac function
• •Corrected QTc must be \<480 milliseconds