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

Inclusion Criteria:

* 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 ≥10mm 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, with evidence of progression on at least two scans (ie, with pseudoprogression ruled out). 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 must have a urine or serum pregnancy test within 24 hours prior to the first dose of trial treatment. If the urine test is positive or cannot be confirmed as negative, then a serum test will need to be negative
* Women of childbearing potential must practice a highly effective method of birth control during treatment and for 160 days after treatment completion. Women of childbearing potential who chose complete abstinence must agree to have a urine or serum pregnancy tests within 24h of each dose of study treatment. If the urine test is positive or cannot be confirmed as negative, then a serum test will need to be negative
* Men who are sexually active with women of childbearing potential must agree to follow instructions for methods of contraception while being treated on the study, and for 165 days after treatment completion. Men must agree to not donate sperm during this time period

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 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
* 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