Clinical trial NCT05864144: A Study of SNS-101 (Anti VISTA) Monotherapy and in Combination With Cemiplimab in Patients With Advanced Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: 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
Sarcoma
Advanced Cancer
Metastatic Cancer
Refractory Cancer
Non Small Cell Lung Cancer
Merkel Cell Carcinoma
Keywords: Solnerstotug
Lead sponsor: Sensei Biotherapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2023-05-18
Enrollment: 169
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse Events - Part A & B
timeFrame: Day 1 through 90 days after the last dose
measure: Determine the Recommended Phase 2 dose or maximum tolerated dose - Part A & B
timeFrame: Approximately 15 months
measure: Objective Response Rate (ORR) - Part C
timeFrame: Day 1 through study completion (approximately 1 year)
Secondary outcomes:
measure: Determine pharmacokinetic profile (maximum concentration) of SNS-101 - Part A, B & C
timeFrame: Day 1 through 30 days after the last dose
measure: Determine pharmacokinetic profile (area under the curve) of SNS-101 - Part A, B & C
timeFrame: Day 1 through 30 days after the last dose
measure: Determine pharmacokinetic profile (total clearance) of SNS-101 - Part A, B & C
timeFrame: Day 1 through 30 days after the last dose
measure: Determine pharmacokinetic profile (terminal half life) of SNS-101 - Part A, B & C
timeFrame: Day 1 through 30 days after the last dose
measure: Number of participants with anti-SNS-101 antibodies post-administration of SNS-101 - Part A, B & C
timeFrame: Day 1 through 30 days after the last dose
measure: Objective Response Rate (ORR) - Part A & B
timeFrame: Day 1 through study completion (approximately 1 year)
measure: Duration of Response (DoR) - Part A, B & C
timeFrame: Day 1 through study completion (approximately 1 year)
measure: Disease Control Rate (DCR) - Part A, B & C
timeFrame: Day 1 through study completion (approximately 1 year)
measure: Progression Free Survival - Part A, B and C
timeFrame: Day 1 through study completion - approximately 1 year (Part A, B & C)
measure: Adverse Events - Part C
timeFrame: Day 1 through study completion (approximately 1 year)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Hematology/Oncology
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center - Anschutz Medical
state: Colorado
city: Louisville
country: United States
facility: Norton Healthcare
state: Kentucky
city: Detroit
country: United States
facility: Henry Ford Cancer
state: Michigan
city: New York
country: United States
facility: Icahn School of Medicine at Mt. Sinai
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania, Perelman Center for Advanced Medicine
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Cancer Center
state: South Dakota
city: Irving
country: United States
facility: NEXT Oncology Dallas
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics (START) San Antonio
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
Study officials:
affiliation: Sensei Biotherapeutics, Inc.
name: Ron Weitzman, MD
role: STUDY_DIRECTOR
References: