Patients will be treated with the combination of BO-112 and pembrolizumab. IT administration of BO-112 will be performed once weekly (QW) for the first 7 weeks and then once every three weeks (Q3W); pembrolizumab Q3W will be administered IV. After enrolment of 40 patients, the sponsor and investigators will review the overall response rate (ORR), durability of response (DOR), disease control rate (DCR) and safety profile, and will decide whether to initiate a subsequent randomized phase of the trial.~The order of administration should be pembrolizumab then IT BO-112. BO-112 will be administered IT at a total dose of 1-2 mg at each administration to 1-8 tumor lesions using tuberculin (TB) syringes (or equivalent) with 20- to 25-gauge needles. The needle type can also be per the investigator's discretion, to best distribute the study drug within the lesion. Repeat IT dosing may occur if the lesion(s) remain(s) palpable or detectable by ultrasound, after which, only pembrolizumab infusion will continue.~BO-112 can be administered IT into multiple accessible lesions amenable to repeat administration using an appropriate syringe and needle type for the location of the lesion(s). The rationale for dosing multiple lesions is to produce an immune response against a wider range of genetic mutations and antigenic diversity than may occur within a single lesion, which in turn is expected to reduce the chance of immune escape by the tumor.
This is a phase 2, single arm, open label, adaptive design study to determine the preliminary anti-tumor activity and confirm the safety of IT BO-112 in combination with intravenous (IV) pembrolizumab. The study will enroll patients with advanced and/or metastatic melanoma that have progressed on anti-PD-1-containing treatment.