On October 17, 2025 Sensei Biotherapeutics, Inc. (Nasdaq: SNSE), a clinical-stage biotechnology company focused on the discovery and development of next-generation therapeutics for cancer patients, reported results from the dose expansion portion of its Phase 1/2 trial evaluating solnerstotug (formerly SNS-101), a conditionally active monoclonal antibody targeting VISTA (V-domain Ig suppressor of T cell activation). The data will be shared today during a mini oral session at the ESMO (Free ESMO Whitepaper) Congress 2025.

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The Phase 1 dose expansion is a multi-center, open-label study evaluating solnerstotug as monotherapy and in combination with Libtayo (cemiplimab), Regeneron’s PD-1 inhibitor. The study enrolled patients with a basket of "hot" tumor types (that typically respond to immunotherapy) (n=44), of whom 41 had previously received and progressed on PD-(L)1 therapy, as well as patients with "cold" tumor types (that typically exhibit primary resistance to immunotherapy) (n=20).

Patients who progress following treatment with PD-(L)1 inhibitors ("secondary resistance") face a particularly poor prognosis, as resistance to immune checkpoint blockade is a significant challenge in oncology. For patients who develop secondary resistance, the likelihood of benefiting from a rechallenge with the same therapy is estimated to be 5% or less.1

Currently, treatment options for PD-(L)1 resistant tumors are limited, with many patients receiving chemotherapy, experimental therapies in clinical trials, or palliative care in the absence of effective alternatives. While historical benchmarks in this setting are limited, docetaxel, which is widely used in the 2nd line post-PD-(L)1 setting for Non-Small Cell Lung Cancer (NSCLC), typically has a 6-month PFS of 10-20% in similar patient populations.2 To date, immune checkpoint inhibitor (ICI) combination therapies have not been approved in this setting.

Emerging Clinical Signal and Favorable Tolerability Profile

As of the September 8, 2025, data cutoff, 35 efficacy-evaluable "hot tumor" patients had received cemiplimab with either 15 mg/kg (n=19) or 3 mg/kg dose (n=16) of solnerstotug. Six clinical responses, including five in patients with PD-(L)1 resistant tumors, occurred at the higher 15 mg/kg solnerstotug dose, and no objective responses were observed at the 3 mg/kg dose.

Among 41 "hot tumor" patients that received and progressed on a prior PD-(L)1 therapy, the overall 6-month PFS rate was 37%, which compares favorably with historical benchmarks in this setting. At 15 mg/kg, 6-month PFS reached 50% among PD-(L)1 resistant patients, surpassing rates historically seen in this treatment-refractory population. At 3 mg/kg, 6-month PFS was 24% among PD-(L)1 resistant patients.

Solnerstotug was well tolerated at both 3 mg/kg and 15 mg/kg doses in combination with cemiplimab:

Only six mild (Grade 1) CRS events were observed across all patients in Phase 1 (n=98), all manageable.
No new safety signals were identified across dose expansion (n=64).
The safety profile remains consistent with prior data and compares favorably to other checkpoint inhibitor combinations in this population.

"We believe solnerstotug’s emerging dose-dependent activity in refractory ‘hot’ tumors, combined with a favorable tolerability profile, support its advancement into Phase 2 studies," said Ron Weitzman, M.D., Chief Medical Officer of Sensei Biotherapeutics. "The data suggest that selective blockade of VISTA within the tumor microenvironment may help re-engage exhausted T cells, even after PD-1 failure, a goal long considered out of reach."

In addition to the "hot" tumor cohorts, 20 patients with Microsatellite Stable Colorectal (MSS CRC) "cold" tumors were treated with either solnerstotug as monotherapy or in combination with cemiplimab (350 mg). No responses were observed and the safety profile was consistent with previously reported data.

Durable Disease Control in "Hot" Tumors Followed by Late Onset Responses

Four out of six responders demonstrated prolonged disease control, followed by a late onset response (occurring between 18 and 54 weeks). PD-(L)1 therapies typically have a time to response of 2–3 months, indicating that the combination of solnerstotug plus cemiplimab has a unique and differentiated pattern of activity.

At the 15 mg/kg dose of solnerstotug, notable responses included:

A Merkel Cell Carcinoma (MCC) patient with a durable complete response at week 18 and a duration of response of 54+ weeks
A Microsatellite Instability-High Colorectal Cancer (MSI-H CRC) patient with a partial response (PR) at week 36 and a 33+ week duration
An NSCLC patient with a tumor proportion score less than 5% that was PD-1 naïve had a PR at week 54 and duration of response of 15+ weeks
An Esophageal Cancer patient with a PR at Week 24 and a duration of response of 6 weeks

"This pattern of delayed, durable responses is unusual among immunotherapies," said Kyriakos Papadopoulos, M.D., Co-Director of Clinical Research at START, San Antonio. "It may indicate that solnerstotug acts through a mechanism that is complementary to PD-(L)1 in resistant tumors."

Next Steps: Planned Phase 2 Studies to Evaluate Efficacy in a Commercially Attractive Indication and Potentially Pursue Accelerated Approval in a PD-1 Resistant Population

Sensei is planning two Phase 2 studies to begin in 2026, subject to FDA feedback and the Company’s ability to raise sufficient capital. The first is expected to be a randomized trial in 2nd line NSCLC where patients have received and failed anti-PD-(L)1 treatment. Patients would be randomized to receive either the combination of solnerstotug + a PD-(L)1 inhibitor or chemotherapy.

The second trial is expected to be a single arm study in PD-(L)1 resistant MCC patients where there is limited therapeutic optionality and potential for accelerated approval, subject to FDA feedback.

"We’re pleased by the emerging signs of dose-related activity, durability, and a favorable safety profile—key characteristics of a potentially differentiated immunotherapy," said John Celebi, President and Chief Executive Officer of Sensei Biotherapeutics. "These results provide a foundation for our planned Phase 2 development program as we work to better define solnerstotug’s role in treating challenging patient populations."

(Press release, Sensei Biotherapeutics, OCT 17, 2025, View Source/news-releases/news-release-details/sensei-biotherapeutics-reports-new-clinical-results-highlighting" target="_blank" title="View Source/news-releases/news-release-details/sensei-biotherapeutics-reports-new-clinical-results-highlighting" rel="nofollow">View Source [SID1234656737])

Investor Webcast Information

Sensei will host an investor webcast on October 20th at 8:00 AM ET, featuring company leadership and Kyriakos Papadopoulos, MD, Co-Director of Clinical Research at START, San Antonio.

Register for the event here. A replay will be available after the webcast on the Investor Relations page of Sensei’s website: View Source