Sensei Biotherapeutics announced preliminary positive results from the dose expansion portion of its Phase 1/2 trial of solnerstotug, a VISTA-targeting monoclonal antibody, in patients with advanced cancer who had progressed on prior PD-(L)1 therapy. The initial data show a 14% overall response rate in patients with “hot” tumors (cancers typically responsive to immunotherapy) and durable responses in some patients, notably in Merkel cell carcinoma (MCC) and microsatellite instability-high (MSI-H) colorectal cancer. These findings are significant because they suggest potential efficacy in a patient population with limited effective treatment options.
This news is important because the observed response rate in the “hot” tumor group is nearly three times higher than the historical ~5% response rate seen with PD-(L)1 rechallenge in this patient population. This suggests that solnerstotug could address a critical unmet medical need for patients who have developed resistance to standard immunotherapy treatments. The durable responses observed further support the potential for solnerstotug to provide meaningful clinical benefit.
The Phase 1 dose expansion study enrolled 60 patients: 40 with “hot” tumors (including NSCLC, head and neck cancer, melanoma, RCC, MCC, MSI-H CRC, and other tumor types) and 20 with “cold” microsatellite stable (MSS) CRC. Of the 21 evaluable “hot” tumor patients, three achieved an objective response: one complete response in an MCC patient, one partial response in another MCC patient, and one partial response in an MSI-H CRC patient. Notably, all responding patients and six additional patients with stable disease and tumor reduction remained on the study at the time of data cutoff, indicating potential for ongoing benefit. No responses were observed in the “cold” tumor group, which is consistent with the known resistance of MSS CRC to checkpoint inhibitors. Solnerstotug was generally well-tolerated, with primarily mild adverse events.
Looking ahead, Sensei plans to initiate a Phase 2 study in Q1 2026, pending sufficient capital. The design of this study will be informed by the ongoing dose expansion results, including biomarker analyses that may help to identify patients most likely to benefit from solnerstotug. These early findings suggest that targeting VISTA could represent a promising new approach for patients with PD-(L)1 resistant cancers, offering a much-needed alternative to chemotherapy or palliative care. Further research will be crucial to confirm these results and to define the optimal role of solnerstotug in the treatment landscape.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
