Xilio’s Vilastobart Shows Potential in Hard-to-Treat MSS Colorectal Cancer

Xilio Therapeutics recently announced encouraging early data from its Phase 1C trial for vilastobart (XTX101), an innovative anti-CTLA-4 therapy designed to target tumors, in combination with atezolizumab. This combination was tested in patients with advanced solid tumors, including those that are traditionally resistant to immunotherapy, such as MSS colorectal cancer. Early findings demonstrated two unconfirmed partial responses, including one case where a metastatic liver lesion completely resolved. This result is notable, given that liver metastases in MSS colorectal cancer patients have proven particularly resistant to current immunotherapies.

Xilio’s CEO, Dr. René Russo, highlighted that these early results may point to vilastobart’s unique potential for treating challenging "cold" tumors. The company’s goal is to establish a treatment option for MSS colorectal cancer patients, a group with limited therapeutic options. The trial included 17 patients treated with doses of vilastobart ranging from 75 mg to 150 mg every six weeks and 1200 mg of atezolizumab every three weeks. Notably, the majority of these patients had already undergone several rounds of prior treatments, underlining the promising results seen in this pre-treated population.

On the safety front, the combination was generally well-tolerated. Across all doses, there were no Grade 4 or 5 treatment-related adverse events (AEs), and only three Grade 3 treatment-related AEs were reported, including colitis, diarrhea, and ALT increase. A single patient discontinued treatment due to adverse effects, suggesting a potentially safer profile for vilastobart compared to traditional anti-CTLA-4 therapies when used with PD-(L)1 inhibitors.

Based on these Phase 1C findings, Xilio selected an initial recommended Phase 2 dose (RP2D) of 100 mg for vilastobart with atezolizumab. The Phase 2 trial, which focuses on patients with metastatic MSS colorectal cancer, is ongoing. The company anticipates releasing initial Phase 2 data by the end of 2024 and further findings in early 2025. Xilio will discuss these updates during a conference call, with more details available on their investor relations webpage.