Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101, a novel anti VISTA IgG1 monoclonal antibody as monotherapy or in combination with cemiplimab in patients with advanced solid tumors.

This is a first-in-human, Phase 1/2 open-label, multi-center, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101, a novel anti VISTA IgG1 monoclonal antibody as monotherapy or in combination with cemiplimab in patients with advanced solid tumors.

This study is being conducted in three parts:

• Part A: Phase 1 Monotherapy Dose Escalation and Dose Expansion (SNS-101 alone)
• Part B: Phase 1 Combination Dose Escalation and Dose Expansion (SNS-101 in combination with cemiplimab)
• Part C: Phase 2 Cohort Expansion (SNS-101 alone or in combination with cemiplimab)

Once the dose escalation portion is complete enrollment will expand to targeted tumor types:

• Approximately 10 patients with colorectal cancer (CRC) will be enrolled in the Monotherapy Dose Expansion.

  o Additional tumor types and doses may be considered upon consultation with the Sponsor.

• Approximately 50 patients with CRC, head and neck cancer (H&N), melanoma, and non-small cell lung cancer (NSCLC) will be enrolled in the Combination Dose Expansion.

  • A minimum of 8 and a maximum of 10 CRC patients will be enrolled in the Combination Dose Expansion.
  • Additional tumor types and doses may be considered upon consultation with the Sponsor.

Key Inclusion Criteria:

• Histologically or cytologically documented locally advanced, unresectable or metastatic solid tumor.

• Having received and failed or was intolerant to standard of care for advanced disease or not eligible for standard of care therapy with the following tumor types for patients in Phase 1 dose expansion cohorts:

  1. Microsatellite Stable (MSS) CRC (both monotherapy and combination cohorts); no more than 3 lines of prior systemic therapy for metastatic disease.
  2. H&N cancer (combination cohort only); no more than 2 lines of prior systemic therapy for metastatic disease.
  3. Melanoma (combination cohort only); no more than 3 lines of prior systemic therapy for metastatic disease, including at least 1 prior treatment with a BRAF inhibitor for patients with a BRAF mutation.
  4. NSCLC (combination cohort only); no more than 2 lines of prior systemic therapy for metastatic disease, including at least 1 prior treatment with a targeted therapy for patients with a mutation such as EGFR, ALK, KRAS, or RET.
  5. Patients with H&N cancer, melanoma, and NSCLC (or additional tumor types that typically respond to PD1/PD-L1 monotherapy) must have received a prior PD1/PD-L1 where best response was stable disease and progression occurred during treatment or within 3 months of last dose of PD1/PD-L1.

Additional tumor types and doses may be considered.

• Measurable disease
• ECOG performance status 0 or 1.
• Life expectancy of ≥ 3 months.
• Willing to provide pre-treatment (archival or fresh) and on-treatment tumor biopsy samples.
• Adequate organ function
• Women of childbearing potential and fertile males with WOCBP partners must use highly effective contraception during the study and for 180 days after the study. Patients must agree not to donate eggs (ova, oocytes) or sperm during the study.

Key Exclusion Criteria:

• Use of anti-PD-1/PD-L1 targeting monoclonal antibody therapy, monoclonal antibody therapy, chemotherapy, biologic, investigational, or radiotherapy within 2 weeks of Cycle 1 Day 1.
• Clinically significant unresolved toxicities from prior anticancer therapy.
• Grade 3 or higher immune-related adverse event on prior PD-1/PD-L1 blockade or prior agents targeting stimulatory or co-inhibitory T cell receptor.
• Known other previous/current malignancy requiring treatment within ≤ 2 years except for limited disease treated with curative intent, such as carcinoma in situ, squamous or basal cell skin carcinoma, or superficial bladder carcinoma.
• Known asymptomatic or symptomatic brain metastasis or leptomeningeal disease.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
• Women who are pregnant or breastfeeding.