A Study of SNS-101 (Anti VISTA) Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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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 (SNS-101 alone) Part B: Phase 1 Combination Dose Escalation (SNS-101 in combination with cemiplimab) Part C: Phase 2 Expansion Cohorts (SNS-101 alone or in combination with cemiplimab)

Official Title
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A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SNS-101 (Anti VISTA) as Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors

Conditions
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Sarcoma, Solid Tumor, Adult, Advanced Solid Tumor, Head and Neck Cancer, Breast Cancer, Colon Cancer, Pancreatic Cancer, Gastric Cancer, Esophageal Cancer, Prostate Cancer, Uterine Cancer, Cervix Cancer, Ovarian Cancer, Kidney Cancer, Bladder Cancer, Thyroid Cancer, Melanoma, Advanced Cancer, Metastatic Cancer, Refractory Cancer

Intervention / Treatment
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* Drug: SNS-101 (anti-VISTA)
* Drug: Cemiplimab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically or cytologically documented locally advanced, unresectable or metastatic solid tumor. Refractory or intolerant to standard of care for advanced disease or not eligible for standard of care therapy. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A - SNS-101 Monotherapy<br>SNS-101 IV alone every 21 days. Patients will enroll in dose escalation cohorts. | Drug: SNS-101 (anti-VISTA)<br>* SNS-101 IV every 21 days.<br>|
| Experimental: Part B - SNS-101 in combination with cemiplimab<br>SNS-101 IV and cemiplimab IV every 21 days. Patients will enroll in dose escalation cohorts. | Drug: SNS-101 (anti-VISTA)<br>* SNS-101 IV every 21 days.<br>Drug: Cemiplimab<br>* Cemiplimab IV every 21 days.<br>|
| Experimental: Part C - Expansion Cohorts - SNS-101 alone or in combination with cemiplimab<br>SNS-101 IV alone or in combination with cemplimab IV every 21 days at the RP2D. | Drug: SNS-101 (anti-VISTA)<br>* SNS-101 IV every 21 days.<br>Drug: Cemiplimab<br>* Cemiplimab IV every 21 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events - Part A & B | Incidence, nature and severity of treatment-related adverse events | Day 1 through 90 days after the last dose | 
| Determine the Recommended Phase 2 dose or maximum tolerated dose - Part A & B | Incidence and nature of dose-limiting toxicities | Approximately 15 months | 
| Objective Response Rate (ORR) - Part C | Measured by RECIST 1.1 and iRECIST | Day 1 through study completion (approximately 1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine pharmacokinetic profile (maximum concentration) of SNS-101 - Part A, B & C | Measured by maximum concentration | Day 1 through 30 days after the last dose | 
| Determine pharmacokinetic profile (area under the curve) of SNS-101 - Part A, B & C | Measured by area under the curve | Day 1 through 30 days after the last dose | 
| Determine pharmacokinetic profile (total clearance) of SNS-101 - Part A, B & C | Measured by total clearance | Day 1 through 30 days after the last dose | 
| Determine pharmacokinetic profile (terminal half life) of SNS-101 - Part A, B & C | Measured by serum terminal half-life | Day 1 through 30 days after the last dose | 
| Number of participants with anti-SNS-101 antibodies post-administration of SNS-101 - Part A, B & C | Measured by anti-SNS-101 neutralizing anti-drug antibodies | Day 1 through 30 days after the last dose | 
| Objective Response Rate (ORR) - Part A & B | Measured by RECIST 1.1 and iRECIST | Day 1 through study completion (approximately 1 year) | 
| Duration of Response (DoR) - Part A, B & C | Measured by RECIST 1.1 and iRECIST | Day 1 through study completion (approximately 1 year) | 
| Disease Control Rate (DCR) - Part A, B & C | Measured by RECIST 1.1 and iRECIST | Day 1 through study completion (approximately 1 year) | 
| Progression Free Survival - Part A, B and C | Measured by RECIST 1.1 and iRECIST | Day 1 through study completion - approximately 1 year (Part A, B & C) | 
| Adverse Events - Part C | Incidence, nature and severity of treatment-related adverse events | Day 1 through study completion (approximately 1 year) |