Sensei Biotherapeutics Shows Promising Phase 1 Data for SNS-101

Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a company specializing in immuno-oncology, has revealed favorable data from the dose escalation phase of its Phase 1/2 clinical trial for SNS-101. This investigational treatment is a conditionally active human monoclonal antibody targeting the immune checkpoint VISTA (V-domain Ig suppressor of T cell activation).

Dr. Shiraj Sen, a principal investigator at NEXT Oncology, Dallas, and Medical Oncologist, expressed optimism about the drug’s performance. He highlighted the absence of dose-limiting toxicities and noted that SNS-101 has reached its maximum planned dosage without significant adverse effects. The drug has shown potential in addressing previous challenges faced by VISTA-targeted therapies. Encouraging signs of clinical activity were observed in patients with advanced solid tumors, particularly in those with microsatellite stable colorectal and endometrial cancers, areas where responses to traditional immunotherapies are typically rare.

The clinical trial aimed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of SNS-101. It involved both monotherapy and combination therapy with Regeneron’s PD-1 inhibitor Libtayo® (cemiplimab) in patients with advanced solid tumors that are either primary candidates unsuitable for immunotherapy or have developed resistance to PD-1 therapy.

A total of 34 patients participated, with 16 receiving SNS-101 alone and 18 receiving it in combination with cemiplimab. Notably, 85% of these patients had tumor types that are generally unresponsive to PD-1 monotherapy, often referred to as "cold" tumors.

Data up to April 30, 2024, indicated promising clinical activity across various tumor types. For instance, one patient with microsatellite stable (MSS) endometrial cancer showed a confirmed partial response with a 59% tumor reduction and remained on the study for over 30 weeks. Another MSS colorectal cancer patient showed a 27% tumor reduction and remained on the study for 18 weeks. Additionally, a pembrolizumab-resistant renal cell carcinoma patient and a pembrolizumab-resistant human papillomavirus (HPV)+ head and neck cancer patient showed tumor regressions of 18% and 17%, respectively.

Preclinical studies suggested that therapeutic doses of SNS-101 at 3mg/kg or higher are effective. Initial pharmacodynamic analysis indicated dose-dependent changes in T-cell populations, suggesting a pharmacological impact on T-cell subsets.

SNS-101 demonstrated a favorable pharmacokinetic profile with linear elimination kinetics and dose-proportional exposure increases, supporting a three-week dosing schedule. This consistency aligned with the absence of target-mediated drug disposition (TMDD), a common issue in non-conditionally active anti-VISTA antibodies.

Safety data revealed that SNS-101 was well-tolerated as both a monotherapy and in combination with cemiplimab, without any dose-limiting toxicities. Most adverse events (AEs) were mild to moderate (Grade 1 or 2). Two patients experienced Grade 1 cytokine release syndrome (CRS) at the highest dose level, and four patients in the combination cohort had immune-mediated events. No significant changes were noted in key inflammatory cytokine levels across the study cohorts.

Ron Weitzman, Chief Medical Officer of Sensei Biotherapeutics, emphasized that the dose escalation phase addressed critical challenges associated with targeting VISTA, including severe safety and pharmacokinetic issues. He noted the promising clinical activity, particularly in tumor types resistant to PD-1 monotherapy, and expressed optimism about the trial's expansion phase.

Patient enrollment is ongoing for the dose expansion phase, with initial data expected by the end of 2024. The findings will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

Sensei Biotherapeutics continues to focus on developing innovative cancer treatments through its TMAb™ platform, which aims to modulate immunosuppressive and immunostimulatory signals within the tumor microenvironment.