1078TiP - Phase I/II, 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 (pts) with advanced solid tumors

Background

SNS-101 is a novel monoclonal antibody, selectively targeting the active/protonated form of V-domain Ig suppressor of T-cell activation (VISTA) found in the low pH of the tumor microenvironment. SNS-101 selectively binds with high affinity to VISTA at pH 6.0 and blocks the interaction between its receptor, the T-cell checkpoint P-selectin glycoprotein ligand-1. Based on preclinical data, SNS-101, either as monotherapy or in combination therapy with a PD-1 blocker, cemiplimab, is expected to exhibit an acceptable tolerability profile and demonstrate anti-tumor activity in pts with advanced solid tumors.

Trial design

This is a first in human, open-label, multi-center, dose escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of SNS-101, as monotherapy or in combination with cemiplimab in pts with advanced solid tumors. This study is being conducted in 3 parts: Part A (∼25 pts): Phase 1 (P1) Monotherapy Dose Escalation (SNS-101 alone) Part B (∼24 pts): P1 Combination Dose Escalation (SNS-101 + cemiplimab) Part C (∼80 pts): Phase 2 (P2) Expansion Cohorts (SNS-101 ± cemiplimab) Dose escalation/de-escalation will proceed following the Bayesian Optimal Interval Design until the Maximum Tolerated Dose (MTD)/Recommended phase 2 Dose (RP2D) is determined. Tumor imaging will be performed every 6 weeks. All pts will receive SNS-101 ± cemiplimab as intravenous infusion(s) every 3 wks and may continue until confirmed progressive disease or unacceptable toxicity. Primary objectives include safety, tolerability and RP2D/MTD (P1); and to evaluate anti-tumor activity (P2). Key eligibility includes histologically or cytologically locally advanced, unresectable or metastatic solid tumor, measurable disease, Eastern Cooperative Oncology Group ≤1 and pre-treatment/on-treatment tumor biopsy samples. Tumor types for P2 will be determined based on data from P1 and emerging results from preclinical studies/scientific data. The IND cleared in April 2023 and the study is open for enrollment.

Clinical trial identification

SNS-101-2-1.

Editorial acknowledgement

Legal entity responsible for the study

Sensei Biotherapeutics.

Funding

Sensei Biotherapeutics.

Disclosure

K.P. Papadopoulos: Financial Interests, Personal, Advisory Board: Turning Point Therapeutics, Bicycle, Basilia; Financial Interests, Institutional, Full or part-time Employment: START; Financial Interests, Personal, Ownership Interest: START; Financial Interests, Institutional, Local PI, For conduct of clinical trial: 3D Medicines, AbbVie, ADC Therapeutics, Amgen, Anheart Therapeutics, Bayer, Daiichi Sankyo, EMD Serono, F-Star, Incyte, Jounce Therapeutics, Lilly, Linnaeus Therapeutics, Merck, Mersana, Mirati Therapeutics, Pfizer, Regeneron Pharmaceuticals, Revalution Medicines, Syros Pharmaceuticals, Tempest Therapeutics, Treadwell Therapeutics. S. Sen: Financial Interests, Personal, Steering Committee Member: Boehringer Ingelheim, Roche; Non-Financial Interests, Institutional, Principal Investigator: ABM Therapeutics, Boehringer Ingelheim, Centessa Pharmaceuticals, Ideaya Biosciences, OncoResponse, Parthenon Biotherapeutics, Pyxis Oncology, Sensei Biotherapeutics, Zentalis Pharmaceuticals. D. Smith: Financial Interests, Institutional, Full or part-time Employment: Sensei Bio; Financial Interests, Personal, Stocks/Shares: Sensei Bio. E. van der Horst: Financial Interests, Personal, Officer, CSO: Sensei Biotherapeutics; Financial Interests, Personal, Stocks/Shares, CSO: Sensei Biotherapeutics. All other authors have declared no conflicts of interest.