Xilio Therapeutics Releases Initial Phase 1C Data on Vilastobart with Atezolizumab in Advanced Solid Tumors

Xilio Therapeutics, Inc., a clinical-stage biotechnology company focused on developing cancer therapies, has announced preliminary clinical data from its ongoing Phase 1C trial. This trial is evaluating vilastobart (XTX101), a tumor-activated, Fc-enhanced anti-CTLA-4, in combination with atezolizumab (Tecentriq®) for patients with advanced solid tumors. The data will be shared in a poster presentation at the Society for Immunotherapy of Cancer (SITC) 39th Annual Meeting in Houston, Texas.

Vilastobart has shown promising initial results, particularly in patients with traditionally immune-resistant tumors, such as microsatellite stable (MSS) colorectal cancer. René Russo, Pharm.D., President and CEO of Xilio, expressed optimism about the safety profile and the early responses, including the complete resolution of a metastatic liver lesion in one patient with MSS colorectal cancer. This type of cancer often has liver metastases which are typically resistant to current immunotherapy treatments, highlighting a significant unmet need.

Dr. Diwakar Davar, the lead author of the study, noted the growing incidence of MSS colorectal cancer in younger adults and the lack of effective treatment options as major challenges in oncology. He emphasized that the early data for vilastobart are encouraging, showing meaningful anti-tumor activity in patients with tumors resistant to immunotherapy, and suggesting vilastobart could be a next-generation anti-CTLA-4 therapy when combined with PD-(L)1 inhibitors.

As of October 7, 2024, 17 patients had been treated with vilastobart at dosages between 75 mg to 150 mg every six weeks, combined with atezolizumab at 1200 mg every three weeks. These patients had various tumor types including MSS CRC, MSI-H CRC, non-small cell lung cancer, esophageal cancer, ampullary carcinoma, and abdominal cancer.

The median age of the patients was 69 years, and they were generally heavily pre-treated, with 83% having received three or more prior lines of therapy. Seven patients continued treatment, while 10 discontinued.

The combination therapy was generally well-tolerated, with minimal immune-related adverse events. No Grade 4 or 5 treatment-related adverse events were reported. One patient experienced a dose reduction due to a treatment-related adverse event, and another discontinued both treatments for the same reason. Only three patients experienced Grade 3 treatment-related adverse events, including increases in alanine aminotransferase (ALT), diarrhea, colitis, and blood alkaline phosphatase (ALP).

The most common treatment-related adverse events across all dose levels were infusion-related reactions, increases in aspartate aminotransferase (AST), ALT, and lipase, as well as diarrhea, fatigue, and blood ALP increase.

A patient with MSS CRC and a metastatic liver lesion showed a partial response, including complete resolution of the liver lesion, after being treated with vilastobart and atezolizumab. Another patient with ampullary carcinoma also showed a partial response and a significant decrease in serum tumor marker CA 19-9 levels.

Based on these initial findings, a recommended Phase 2 dose (RP2D) for vilastobart at 100 mg every six weeks in combination with atezolizumab at 1200 mg every three weeks has been selected. Xilio Therapeutics continues to enroll patients in the Phase 1C dose escalation and Phase 2 trials for this combination therapy in patients with metastatic MSS CRC, including those with and without liver metastases.

Initial Phase 2 data for approximately 20 patients are expected in the fourth quarter of 2024, with additional data for a total of around 40 patients anticipated in the first quarter of 2025.

Vilastobart, an investigational monoclonal antibody, is designed to activate specifically within the tumor microenvironment. Xilio entered a collaboration with Roche in 2023 to evaluate vilastobart with atezolizumab in a Phase 1/2 trial. The company aims to develop therapies that improve outcomes for cancer patients by localizing anti-tumor activity and minimizing systemic side effects.

Xilio Therapeutics remains committed to advancing its pipeline of innovative immuno-oncology therapies and optimizing treatments for people living with cancer.