Study of PULSAR-ICI +/- IMSA101 in Patients with Oligoprogressive Solid Tumor Malignancies

Inclusion Criteria: 1. Male or female patients ≥ 18 years of age 2. Signed informed consent and mental capability to understand the informed consent 3. Histologically or cytologically documented solid tumor malignancies demonstrating new progression through prior anti-cancer therapy, with a prior 2 months of clinical stability (with at least Stable Disease), with radiographically documented presence of ≤ 6 metastatic lesions consistent with the diagnosis of "oligoprogressive" disease that are technically amenable to PULSAR 4. Patient's disease must be evaluable per RECIST Version 1.1 5. All metastatic lesions amenable to administration of radiotherapy, at the discretion of the investigator 6. Must have at least one single pre-defined progressing lesion/lesion site (longest diameter ≥ 10 mm and ≤ 50 mm) suitable for intra-tumoral injection 7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 8. Electrocardiogram (ECG) without evidence of clinically meaningful conduction abnormalities or active ischemia as determined by the investigator 9. Acceptable organ and marrow function as defined below: * Absolute neutrophil count (ANC) \> 1,500 cells/μL * Platelets \> 50,000 cells/μL * Total bilirubin ≤ 1.5 times (×) the upper limit of normal (ULN) * Aspartate aminotransferase (AST)/alanine aminotransaminase (ALT) ≤ 2.5 × ULN. If liver metastases are present, AST/ALT \< 5 × ULN * Serum creatinine \< 1.5 mg/dL and a measured creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula * Prothrombin time (PT)/partial thromboplastin time (PTT) ≤ 1.5 × ULN 10. Women of child-bearing potential (defined as a female who has experienced menarche and who has not undergone successful surgical sterilization \[hysterectomy, bilateral salpingectomy, or bilateral oophorectomy\]) or is not postmenopausal (defined as amenorrhea for at least 12 consecutive months with an appropriate clinical profile at the appropriate age, eg, greater than 45 years) must have a negative serum pregnancy test prior to first dose of study treatment 11. Male and female patients with reproductive potential must agree to use two forms of highly effective contraception throughout the study Exclusion Criteria: 1. Prior receipt of stimulator of interferon genes (STING) agonist 2. Prior receipt of therapeutic radiotherapy to all progressive lesions intended for PULSAR treatment 3. Anti-cancer therapy, except pembrolizumab and nivolumab, within 4 weeks or \< 5 half-lives of the first dose of study treatment 4. Existence of primary tumor that requires therapeutic treatment beyond the provided immune checkpoint inhibitor drug 5. Failure to recover, to Grade 1 or less, from clinically significant AEs due to prior anti-cancer therapy, as judged by the investigator 6. Previous life-threatening (Grade 4) immune-related adverse event (irAE) 7. Known untreated brain metastases or treated brain metastases that have not been stable (scan showing no worsening of central nervous system \[CNS\] lesion\[s\] and no requirement of corticosteroids) ≥ 4 weeks prior to study enrollment 8. Existence of actionable mutations that are eligible for a mutation-targeting drug that represents standard-of-care 9. Baseline prolongation of QT/corrected QT (QTc) interval (QTc interval \> 470) 10. Uncontrolled intercurrent illness (including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations) that in the opinion of the investigator would limit compliance with study requirements 11. Women who are pregnant or breastfeeding 12. Sponsor reserves the right to exclude any patient from the study on the basis of pre-study medical histories, physical examination findings, clinical laboratory results, prior medications, or other entrance criteria