Solnerstotug Shows Promising Preliminary Data in PD-L1 Resistant Tumors

Among 21 efficacy-evaluable patients with “hot” tumors, those that typically respond to immunotherapy but experienced disease progression following prior PD-L1 therapy, solnerstotug elicited an ORR rate of 14% and a disease control rate of 62%.

Solnerstotug (SNS-101) with or without cemiplimab (Libtayo) showed promising preliminary dose expansion data as a treatment for PD-L1–resistant tumors, eliciting an objective response rate (ORR) nearly 3 times higher than historical PD-L1 rechallenge response rates, according to a news release from the drug’s developers, Sensei Biotherapeutics.¹

Findings from the phase 1/2 study (NCT05864144) revealed that among 21 efficacy-evaluable patients with “hot” tumors, those that typically respond to immunotherapy but experienced disease progression following prior PD-L1 therapy, solnerstotug elicited an ORR rate of 14% (n = 3) and a disease control rate of 62% (n = 13).

Responses to treatment included: a durable complete response (CR) in a patient with merkel cell carcinoma (MCC) treated with 15 mg/kg of solnerstotug plus cemiplimab continuing treatment after 42 weeks; a partial response (PR) in a patient with MCC treated with 15 mg/kg of solnerstotug plus cemiplimab continuing after 12 weeks; and a PR in a patient with microsatellite instability-high (MSI-H) colorectal cancer (CRC) treated with 15 mg/kg of solnerstotug plus cemiplimab who continues treatment after 36 week. The latter initially had durable stable disease (SD) but converted to a PR at week 36.

Additional findings revealed that 6 patients with prior PD-L1 resistance with stable disease remained on treatment after 12 weeks, and tumor reductions were as high as 17% in this population. Furthermore, all patients who were PD-L1 resistant with tumor shrinkage remained on treatment. Although none of 17 patients with “cold” tumors, defined as those with PD-L1 non-responsive microsatellite stable (MSS) CRC, achieved a CR or PR, the results were consistent with prior checkpoint therapy in this indication.

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

A total of 40 patients with “hot” tumors were enrolled on the study, all of whom received the combination of solnerstotug at a dose of either 3 mg/kg or 15 mg/kg of cemiplimab. Twenty patients with “cold” tumors were enrolled, 10 of whom received 15 mg/kg of solnerstotug as a monotherapy and 10 of whom received 15 mg/kg of solnerstotug in combination with cemiplimab.

The coprimary end points for the phase 1 portion of the study were adverse effect (AE) occurrence and the recommended phase 2 dose (RP2D) or maximum tolerated dose (MTD).² The primary end point of the phase 2 portion of the study is ORR. Secondary end points include pharmacokinetics of solnerstotug, duration of response, DCR, progression-free survival, and phase 1 ORR.

No dose-limiting toxicities were seen with solnerstotug in patients with PD-L1 resistant tumors (n = 60), and most adverse effects were grades 1 or 2 in severity. Four (7%) cases of grade 1 cytokine release syndrome (CRS) were observed on trial but were mild in severity and managed. Additionally, 2 patients in the combination group experienced immune-mediated AEs.

Patients were eligible for study enrollment if they had; histologically or cytologically documented, locally advanced, unresectable, or metastatic solid tumors; progressed following standard of care (SOC) for advanced disease or were not eligible for SOC; and ECOG performance status score of 0 or 1; and a life expectancy of at least 3 months; among other criteria.

References

1. Sensei Biotherapeutics reports favorable preliminary dose expansion data for solnerstotug in PD-(L)1 resistant tumors. News release. Sensei Biotherapeutics. March 28, 2025. Accessed March 28, 2025. https://tinyurl.com/54w7t8pm
2. A study of SNS-101 (anti VISTA) monotherapy and in combination with cemiplimab in patients with advanced solid tumors. ClinicalTrials.gov. Updated March 25, 2025. Accessed March 28, 2025. https://tinyurl.com/mry4kyx3