The purpose of this study is to determine:
1. The highest dose of the trial intervention that targets neuroendocrine tumors and is tolerated by patients. 2. The highest frequency of dosing of the trial intervention that targets neuroendocrine tumors and is tolerated by patients. 3. The highest dose and frequency of dosing of the trial intervention that targets neuroendocrine tumors with at least the same degree of effectiveness and tolerability as currently available (standard of care) treatments for patients with neuroendocrine tumors.
Male or female patients, 18 years of age or older at the time of consent.
Life expectancy of 6 months or greater as assessed by the treating oncologist.
Have advanced metastatic disease that has progressed on at least one line of available therapy.
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.
Any active second malignancy within the 2 years prior to the screening visit, unless the patient has undergone curative surgery for the tumors such as in situ cervical cancer or squamous cell cancer of the skin.
Has had cytotoxic chemotherapy or radiation therapy within 3 weeks; and less than 5 half-lives or 6 weeks, whichever is shorter, from prior biologic therapies, prior to the first dose of SVV-001.
Has undergone a major surgical procedure (as defined by the Investigator) or significant traumatic injury within 28 days prior to the first dose of SVV-001.
Has any physical abnormality of the tissue/organ to be biopsied that would put the patient at increased risk of bleeding secondary to the injection and/or biopsy.
Sequential
Seneca Valley Virus-001 (SVV-001)
Biological/VaccineSVV-001 will be administered intratumorally as a single dose on Day 1; or as multiple doses on Days 1, 15, 29, 43, 57, and 71. The virus dose levels per SVV-001 treatment are as follows: * 2.2 × 10\^8 Viral Genomes (VG) (starting dose) * 2.2 × 10\^9 VG * 2.2 × 10\^10 VG
Nivolumab
DrugNivolumab will be administered via intravenous (IV) injection at a dose of 240 mg, once every two weeks starting on Day 15 until Day 85 during SVV-001 therapy. Nivolumab will be administered once every four weeks during the maintenance period for up to 2 years.
Ipilimumab
DrugIpilimumab will be administered via intravenous (IV) injection at a dose of 1 mg/kg, once every six weeks starting on Day 15 until Day 85 during SVV-001 therapy. Participants will continue on 1 mg/kg ipilimumab IV every 6 weeks for two additional doses or unacceptable toxicity and/or participant withdrawal.
Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose
MTD is defined as the highest dose of SVV-001 evaluated for which estimated toxicity rate is the closest to the target toxicity rate as assessed by treating physician using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The MTD will be established as the recommended phase 2 dose (RP2D).
Number of Participants Experiencing Dose Limiting Toxicities (DLTs): Part 1 Only
The number of participants experiencing dose limiting toxicities (DLTs) in Part 1 will be reported. DLTs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
Number of Participants Experiencing Treatment-Related Serious Adverse Events (SAEs)
The number of participants experiencing treatment-related serious adverse events (SAEs) after starting study therapy will be reported. SAEs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
Number of Participants Experiencing Treatment-Related Adverse Events (AEs)
The number of participants experiencing treatment-related adverse events after starting study therapy will be reported. AEs will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
Progression-Free Survival (PFS) Measured by RECIST
Progression-Free Survival (PFS) among study participants will be reported. PFS will be assessed in months (6 and 12 months) from start of treatment according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Progression-Free Survival (PFS) Measured by iRECIST
Progression-Free Survival (PFS) among study participants will be reported. PFS will be assessed in months (6 and 12 months) from start of treatment according to immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).
Overall Response Rate (ORR) Measured by RECIST
ORR is defined as percentage of evaluable patients achieving complete response (CR) or partial response (PR), as best responses according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Overall Response Rate (ORR) Measured by iRECIST
ORR is defined as percentage of evaluable patients achieving complete response (CR) or partial response (PR), as best responses according to immune-related Response Evaluation Criteria in Solid Tumors (iRECIST).
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Peter Hosein, MD
Lead sponsor
University of Miami Sylvester Comprehensive Cancer Center
Sponsor institution
Seneca Therapeutics
Collaborator
