Xilio Therapeutics, Inc. (Nasdaq: XLO) has announced initial clinical data from its Phase 1C clinical trial evaluating vilastobart (XTX101) in combination with atezolizumab (Tecentriq®) in patients with advanced solid tumors. The data, presented at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting, showed encouraging early evidence of anti-tumor activity, particularly in traditionally immunotherapy-resistant tumors.
Promising Results in 'Cold' Tumors
The Phase 1 combination data for vilastobart and atezolizumab provide promising initial clinical evidence of the potential for the combination in patients with traditionally immunotherapy-resistant tumors, or “cold” tumors, including MSS colorectal cancer. Notably, a patient with microsatellite stable colorectal cancer (MSS CRC) and a metastatic liver lesion achieved a partial response, including complete resolution of the liver lesion. This is particularly significant as the majority of metastatic MSS colorectal cancer patients have liver metastases, which have proven to be resistant to existing immuno-oncology treatments.
Safety and Tolerability
The safety data indicated that the combination of vilastobart and atezolizumab was generally well-tolerated. Across all dose levels, no Grade 4 or Grade 5 treatment-related adverse events (AEs) were reported. Only one patient (6%) experienced a dose reduction due to a treatment-related AE, and only one patient (6%) discontinued treatment of both vilastobart and atezolizumab due to a treatment-related AE.
Clinical Trial Details
As of the data cutoff date of October 7, 2024, 17 patients had been treated with the combination of vilastobart at doses ranging from 75 mg to 150 mg once every six weeks (Q6W) and atezolizumab at 1200 mg once every three weeks (Q3W). Tumor types included MSS CRC (n=12) and microsatellite instability high (MSI-H) CRC, non-small cell lung cancer (NSCLC), esophageal cancer, ampullary carcinoma and cancer of the abdomen (n=1 each). The median age was 69 years (ranging from 39 to 77 years), and patients were generally heavily pre-treated, with 83% having received three or more prior lines of anti-cancer therapy.
Vilastobart: A Tumor-Activated Anti-CTLA-4
Vilastobart is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated in the tumor microenvironment (TME). Xilio entered into a co-funded clinical trial collaboration with Roche to evaluate vilastobart in combination with atezolizumab in a multi-center, open-label Phase 1/2 clinical trial.
Next Steps
Xilio continues to enroll patients in Phase 1C dose escalation for the combination of vilastobart at the 150 mg Q6W dose level and atezolizumab at 1200 mg Q3W. The company is also currently enrolling patients in its ongoing Phase 2 clinical trial evaluating the combination of vilastobart and atezolizumab at the initial combination RP2D in patients with metastatic MSS CRC, including patients with and without liver metastases. Initial Phase 2 data for the combination in approximately 20 patients with metastatic MSS CRC is expected in the fourth quarter of 2024, with additional Phase 2 data for the combination in a total of approximately 40 patients with metastatic MSS CRC in the first quarter of 2025.
