Solnerstotug Demonstrates Early Efficacy in PD-L1 Resistant Tumors

Sensei Biotherapeutics announces favorable initial results from the dose expansion portion of its phase 1/2 trial which is evaluating solnerstotug (formerly SNS-101) in PD-L1 resistant tumors, according to a news release from the company.

“Checkpoint inhibitor resistance remains a significant challenge for patients with advanced cancer, with limited treatment options beyond chemotherapy or clinical trials,” Dr. Ron Weitzman, Chief Medical Officer of Sensei Biotherapeutics, said in the news release. “Historically, patients who progress on PD-L1 therapy are estimated to have a 5% or less likelihood of response to PD-L1 rechallenge, making this an extremely difficult-to-treat population, and a large unmet medical need. The initial 14% response rate seen with solnerstotug is nearly three times higher than what would typically be expected in this setting. We believe these early data suggest solnerstotug may provide a meaningful clinical benefit in select tumor types, and we look forward to further evaluating its potential in phase 2.”

Key findings included a 14% overall response rate in three patients and a 62% disease control rate in 13 patients among 21 evaluable PD-L1–resistant “hot” tumor patients.

One patient with Merkel cell carcinoma (MCC) achieved a durable complete response with 15 milligrams per kilogram (mg/kg) solnerstotug and Libtayo (cemiplimab) and remains on treatment at 42 or more weeks after previously receiving PD-L1 therapy for 15 months in the adjuvant setting before progressing.

Another patient with MCC achieved a partial response at Week 12 with the same combination and remains on treatment at 12 or more weeks after prior checkpoint therapy, including PD-1 and CTLA-4 inhibitors, with a best response of stable disease before progression.

A patient with microsatellite instability-high colorectal cancer (MSI-H CRC) achieved a partial response at week 36 following durable stable disease through treatment and remains on therapy at 36 or more weeks. This patient had previously received PD-L1 therapy for more than four years, achieving a complete response before progressing.

Additionally, six PD-L1–resistant patients with stable disease remain on treatment past 12 or more weeks, with tumor reductions ranging from 0% to 17%, suggesting durable disease control in a subset of patients, as per the release. All PD-L1–resistant patients with tumor shrinkage remain on therapy, indicating potential for prolonged benefit. No patients with microsatellite stable colorectal cancer (CRC) experienced a complete or partial response, consistent with prior checkpoint therapy outcomes in this “cold” tumor type.

Regarding safety, solnerstotug remains well tolerated, with no dose-limiting toxicities and most side effects being grade 1 (mild) or 2 (moderate). Among 60 patients, four (7%) had grade 1 cytokine release syndrome, all mild and manageable. Two patients in the combination cohort experienced immune-mediated effects.

Solnerstotug is a conditionally active monoclonal antibody targeting VISTA (V-domain Ig suppressor of T cell activation).

A total of 60 patients were enrolled in the trial, of which 40 patients with "hot" tumors, such as non-small cell lung cancer, head and neck cancer, melanoma, renal cell carcinoma, Merkel cell carcinoma, microsatellite instability-high colorectal cancer and other tumor types were included. All received solnerstotug (3 mg/kg or 15 mg/kg) with Libtayo. Eleven had not yet reached the first baseline scan, and eight discontinued the study before any post-baseline scan.

The study also included 20 patients with PD-(L)1 non-responsive microsatellite stable colorectal cancer to assess potential activity in "cold" tumors. Ten received monotherapy with solnerstotug (15 mg/kg), and 10 received solnerstotug (15 mg/kg) with Libtayo. Seventeen were evaluable for efficacy, and three discontinued before any post-baseline scan.

The company plans to initiate a phase 2 study in the first quarter of 2026.

"While we remain in the early stages of evaluating solnerstotug’s therapeutic potential, the observed responses — particularly in MCC and MSI-H CRC — are encouraging given the historically poor prognosis of these patients once they have progressed on checkpoint therapy,” Dr. Shiraj Sen, medical oncologist and Director of Clinical Research at NEXT Oncology - Dallas, and a principal investigator for the solnerstotug study, said in the news release. “Continued clinical evaluation will be key in determining which patients are most likely to benefit from this approach.”

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