SVV-001 With Nivolumab and Ipilimumab in Patients With Poorly Differentiated Neuroendocrine Carcinomas (NEC) or Well-Differentiated High-Grade Neuroendocrine Tumors (NET)

Inclusion Criteria

• •1. Male or female patients, 18 years of age or older at the time of consent.
• •2. Life expectancy of 6 months or greater as assessed by the treating oncologist.
• •3. Have advanced metastatic disease that has progressed on at least one line of available therapy.
• •4. Histologically or cytologically confirmed diagnosis of Grade 3 well-differentiated neuroendocrine tumor (NET) or poorly differentiated neuroendocrine carcinoma (NEC; large-cell neuroendocrine carcinoma, small-cell carcinoma, mixed neuroendocrine non neuroendocrine carcinoma). Note: if an archival tissue sample collected ≤ 2 years from enrollment is unavailable at Screening for diagnostic confirmation, at the Principal Investigator's (PI's) discretion, a screening biopsy will be ordered.
• •5. For patients in Part 1A, in addition to histological or cytological confirmation of NEC or NET (see Inclusion #4), radiological confirmation of tumor is required.
• •6. Parts 1B and 2 only: Measurable disease as determined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or immune-related Response Evaluation Criteria in Solid Tumors (iRECIST). At least one lesion must be suitable for multiple injections (up to 6 injections every 2 weeks) with SVV-001. Lesions for injection must be ≥10 mm in longest diameter and deemed safe and suitable for injection by the Investigator.
• •7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• •8. Recovered to Grade 1 or baseline from any clinically significant toxicity associated with prior treatments (excluding alopecia) prior to initiation of investigational medicinal product (IMP) administration.
• •9. Adequate hematological, renal, and liver function defined as follows:
• •* a. Hepatic:
• •* i. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN) (≤5 × ULN if liver metastases are present)
• •* ii. Serum bilirubin ≤1.5 × ULN (unless due to Gilbert's syndrome or hemolysis)
• •* b. Renal:
• •* i. Creatinine clearance ≥50 mL/minute using Cockcroft Gault equation
• •* c. Hematologic:
• •* i. Absolute neutrophil count ≥1500 cells/µL
• •* ii. Platelet count ≥100,000 platelets/µL
• •* iii. Hemoglobin ≥9.0 g/dL
• •* iv. International normalization ratio (INR) within the institutional normal range
• •* v. Normal prothrombin time (PT) and partial thromboplastin time (PTT)
• •10. For Part 2 Expansion Cohort patients only, patients will submit archival tissue at Screening and undergo a post-treatment biopsy according to the treating institution's guidelines with the following exceptions:
• •* a. If an archival tissue sample collected ≤ 2 years from enrollment is unavailable at Screening, at the PI's discretion, a screening biopsy will be ordered.
• •* b. Participants will not undergo a biopsy procedure for collection of the post-treatment biopsy if, in the discretion of their treating physician, the participant's condition has deteriorated to the point where performance of a biopsy procedure would place the participant at an increased risk for complications beyond what is reasonably expected for a biopsy collected as part of the participant's standard medical care.
• •11. Women of childbearing potential must agree to use a reliable form of contraceptive during the trial treatment period and for at least 7 months following the last dose of IMP.
• •12. Male patients must agree to use an adequate method of contraception during the trial treatment period and for at least 7 months following the last dose of IMP.
• •13. Patient is willing and able to comply with all protocol-required assessments, visits, and procedures.
• •14. Provide written informed consent prior to performing any trial-related procedure.