Advanced Cancer, Advanced Solid Tumor, Bladder Cancer, Breast Cancer, Cervix Cancer, Colon Cancer, Esophageal Cancer, Gastric Cancer, Head and Neck Cancer, Kidney Cancer, Melanoma, Merkel Cell Carcinoma, Metastatic Cancer, Non Small Cell Lung Cancer, Ovarian Cancer, Pancreatic Cancer, Prostate Cancer, Refractory Cancer, Sarcoma, Solid Tumor, Adult, Thyroid Cancer, Uterine Cancer
Conditions
Keywords
Solnerstotug
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. The Phase 1 portion is conducted in two parts; A and B: Phase 2 is planned in Part C. * 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) Once the dose escalation portion was complete, enrollment expanded 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. The Phase 2, Part C Cohort Expansion will further evaluate efficacy at the selected dose(s.). Following completion of the Phase 1 portions of the study, the sponsor decided not to initiate the Phase 2 portion. No participants were enrolled in the planned Phase 2 Part C.
Interventions
DRUGSNS-101 (anti-VISTA)
SNS-101 IV every 21 days.
DRUGCemiplimab
Cemiplimab IV every 21 days.
Sponsors
Sensei Biotherapeutics, Inc.
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events - Part A & B | Day 1 through 90 days after the last dose | Incidence, nature and severity of treatment-related adverse events |
| Determine the Recommended Phase 2 dose or maximum tolerated dose - Part A & B | Approximately 15 months | Incidence and nature of dose-limiting toxicities |
| Objective Response Rate (ORR) - Part C. Part C was never initiated. | Day 1 through study completion (approximately 1 year). | Measured by RECIST 1.1 and iRECIST |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine pharmacokinetic profile (maximum concentration) of SNS-101 - Part A, B.& C. Part C was never initiated. | Day 1 through 30 days after the last dose | Measured by maximum concentration |
| Determine pharmacokinetic profile (area under the curve) of SNS-101 - Part A, B & C. Part C was never initiated. | Day 1 through 30 days after the last dose | Measured by area under the curve |
| Determine pharmacokinetic profile (total clearance) of SNS-101 - Part A, B & C. Part C was never initiated. | Day 1 through 30 days after the last dose | Measured by total clearance |
| Determine pharmacokinetic profile (terminal half life) of SNS-101 - Part A, B & C. Part C was never initiated. | Day 1 through 30 days after the last dose | Measured by serum terminal half-life |
| Number of participants with anti-SNS-101 antibodies post-administration of SNS-101 - Part A, B & C. Part C was never initiated. | Day 1 through 30 days after the last dose | Measured by anti-SNS-101 neutralizing anti-drug antibodies |
| Objective Response Rate (ORR) - Part A & B | Day 1 through study completion (approximately 1 year) | Measured by RECIST 1.1 and iRECIST |
| Duration of Response (DoR) - Part A, B & C. Part C was never initiated. | Day 1 through study completion (approximately 1 year) | Measured by RECIST 1.1 and iRECIST |
| Disease Control Rate (DCR) - Part A, B & C. Part C was never initiated. | Day 1 through study completion (approximately 1 year) | Measured by RECIST 1.1 and iRECIST |
| Progression Free Survival - Part A, B and C. Part C was never initiated. | Day 1 through study completion - approximately 1 year (Part A, B & C) | Measured by RECIST 1.1 and iRECIST |
| Adverse Events - Part C. Part C was never innitiated. | Day 1 through study completion (approximately 1 year) | Incidence, nature and severity of treatment-related adverse events |
Countries
United States
Contacts
STUDY_DIRECTORRon Weitzman, MD
Sensei Biotherapeutics, Inc.
Outcome results
None listed