BO-112 With Pembrolizumab in Unresectable Malignant Melanoma

Inclusion Criteria

• Be willing and able to give written informed consent for the study.
• Be ≥ 18 years of age on day of informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically or cytologically confirmed diagnosis of cutaneous or mucosal melanoma.
• Known BRAF status.
• Have unresectable stage III or stage IV melanoma. Patients must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
• Received at least 6 weeks of standard dosing of an approved anti-PD-1/L1 mAb.
• Demonstrated disease progression (PD) on or after PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than four weeks from the date of the first documented PD, in the absence of rapid clinical progression.
• Progressive disease documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.

i. This determination is made by the investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression.

• Anti-PD-1-based therapy should have been the last line of systemic therapy as part of first line treatment. Prior treatment either in neo or adjuvant setting is allowed (if patient did not develop progressive disease while on receiving it). In the case of patients who develop progressive disease during adjuvant therapy, that treatment will be counted as one prior line, and will be eligible if only that prior line has been administered.
• At least one tumoral lesion that is RECIST 1.1 measurable and amenable for IT injection.
• At least one accessible tumor lesion that is amenable to weekly injection. If liver is a site of injection, presence of at least one additional tumor lesion outside the liver amenable for injection.
• Willingness to provide biological samples required for the duration of the study including a fresh tumor biopsy sample. NOTE: If possible, the biopsied lesion should be a non-target lesion.
• Adequate hematologic and organ function defined by the following laboratory results obtained within 2 weeks prior to the first dose of study treatment:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
• Platelet count ≥ 100 x 10^9/L
• Hemoglobin (Hgb) ≥ 9 g/dL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5x upper limit of normal (ULN) (5 × ULN if presence of liver metastases)
• Serum total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN
• Prothrombin time (PT) (or international normalized ratio [INR]) within normal limits and activated partial prothrombin time (aPTT) within normal limits
• Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 30 mL/min (calculated per institutional standard)
• Female patient of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the injection of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Female patients who are not pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.

Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity from the beginning of the study through 120 days after receiving the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.

Non-pregnant, non-breast-feeding women may be enrolled if they are willing to use 2 methods of birth control or are c