SD-101 and BMS-986178 in Treating Patients with Advanced or Metastatic Solid Malignancies

Inclusion Criteria

• Adult patients aged 18 years or older
• Any advanced/metastatic, non-hematological, extracranial solid tumor malignancy with disease progression after at least one line of standard therapy or for which standard therapy known to prolong survival does not exist
• Patients must have at least two sites of non-osseous disease that are >= 10 mm in diameter, one of which must be accessible for intratumoral injection and tumor biopsies and the other of which must be accessible for needle biopsies by interventional radiology. (Sites have to be deemed safe for repeated access upon IR review, based on anatomic location, size, shape, and accessibility). Liver lesions may not be used as the injection site even if otherwise deemed safe for access
• Patients must have at least one additional site of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, other than the sites selected for intratumoral injection and tumor biopsies
• All patients with tumor types for which anti-PD-1 or anti PD-L1 therapy has been approved should have received such therapy prior to enrollment. Patients with validated driver mutations should have received and progressed on appropriate targeted therapy
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy of at least three months
• Total bilirubin < 1.5 x upper limit of normal (ULN) (unless patient has history of Gilbert’s disease)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN)
• Creatinine < 1.5 x ULN or measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 x ULN
• Absolute neutrophil count (ANC) >= 1,500/mcL
• Hemoglobin >= 9 g/dL without transfusion within the past 4 weeks
• Platelets >= 100,000/mcL
• Prothrombin time (PT)/international normalized ratio (lNR) within normal limits
• Written informed consent obtained from subject
• Patients who have previously received an immune checkpoint inhibitor prior to enrollment must have any immune related toxicities resolved to =< grade 1 or baseline (prior to the checkpoint inhibitor) to be eligible. Patients who developed endocrine adverse events on checkpoint inhibitor are eligible to enter regardless of the Common Terminology Criteria for Adverse Events (CTCAE) Grade resolution as long as the patient is well controlled on endocrine replacement
• Women of childbearing potential (WOCBP) must have a urine or serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotrophin [hCG]) within 72 hours prior to the first dose of trial treatment. If a urine test cannot be confirmed as negative, then a serum test will need to be negative
• WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug BMS-986178 plus additional 160 days post-treatment completion. WOCBP who choose complete abstinence must agree to have urine or serum pregnancy tests (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotrophin [hCG]) within 72 hours (h) of each dose of study treatment. If a urine test cannot be confirmed as negative, then a serum test will need to be negative
• Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug BMS-986178 plus an additional 165 days. In addition, male subjects must be willing to refrain from sperm donation during this time. Azoospermic males are exempt from contraceptive requirements

Exclusion Criteria

• History of grade 2 or higher hypersensitivity reaction to either SD-101 or BMS-986178
• Patients who require immediate treatment or cytoreduction, as deemed by their physician or the study investigators
• Treatment with other anticancer therapy (chemotherapy, small molecule, or radiation therapy) within the past 3 weeks prior to study entry or within the past 6 weeks prior to study entry for immunotherapies
• Use of investigational agent within the past 3 weeks prior to study enrollment
• Major surgery within 4 weeks of enrollment, or a surgical wound that has not fully healed
• Vaccinated with live, attenuated vaccines within 4 weeks of enrollment
• Symptomatic central nervous system (CNS) metastases
• Known bleeding disorder that is deemed to place the patient at unacceptable risk for bleeding complications from intratumoral injection. Patients on anticoagulants and anti-platelet agents other than aspirin are excluded
• Any uncontrolled bacterial, fungal, viral, or other infection
• Active autoimmune disease requiring systemic treatment within the past 2 years, with the exception of patients well controlled on physiologic endocrine replacement
• Treatment with corticosteroids (> 10 mg per day prednisone or equivalent) or other immune suppressive drugs within 14 days prior to initiation of study drug. Steroids for topical ophthalmic, inhaled, or nasal administration are allowed. Patients requiring courses of systemic steroids for 14 consecutive days or less for an acute condition (not for a chronic autoimmune illness) may receive study drug 14 days after steroid therapy
• Prior history of cancer that is unlikely to interfere with the ability to give study treatment or affect the primary outcome or interpretation of the primary outcome of the study. For a history of malignancy treated with curative intent, enrollment should occur at least 2 years after such therapy
• Significant cardiac disease (New York Heart Association [NYHA] class IV congestive heart failure, or unstable angina or myocardial infarction within the past 6 months)
• Human immunodeficiency virus (HIV) positive (+) patients or patients with active hepatitis B or C infection, defined as a positive viral load for HBV or HCV or a positive surface antigen (HBsAg) test for hepatitis B
• Patients who are pregnant or breastfeeding
• Any other medical history, including laboratory results, deemed by the investigator likely to interfere with their participation in the study, or to interfere with the interpretation of the results