Xilio Therapeutics, Inc. (Nasdaq: XLO) has announced initial clinical data from its Phase 1C clinical trial evaluating vilastobart (XTX101), a tumor-activated anti-CTLA-4 antibody, 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 patients with traditionally immunotherapy-resistant tumors.
Encouraging 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 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.
Diwakar Davar, M.D., Associate Professor of Medicine at the UPMC Hillman Cancer Center, highlighted the increasing incidence of MSS colorectal cancer and the lack of effective treatment options. He noted that the initial combination data for vilastobart are encouraging, showing early evidence of meaningful anti-tumor activity in patients with traditionally immunotherapy-resistant tumors.
Phase 1C 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). The median age of patients was 69 years, and 83% had previously received three or more prior lines of anti-cancer therapy. Tumor types included MSS CRC (n=12) and other cancers (n=5).
Safety and Tolerability
The combination of vilastobart and atezolizumab was generally well-tolerated. 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 due to a treatment-related AE. The most common treatment-related AEs (≥10% incidence) were infusion-related reactions (59%), AST increase, ALT increase and lipase increase (18% each), diarrhea, fatigue and blood ALP increase (12% each).
Anti-Tumor Activity
In addition to the patient with MSS CRC and a metastatic liver lesion who achieved a partial response with complete resolution of the liver lesion, a patient with ampullary carcinoma achieved a partial response (unconfirmed) per RECIST (32% reduction in the sum of diameters of target lesions) accompanied by a substantial decrease in the serum tumor marker CA 19-9 (from 700.2 at baseline to 40.8 after 6 weeks of treatment).
Next Steps
The initial Phase 1C data supported the selection of an initial recommended Phase 2 dose (RP2D) for vilastobart at 100 mg Q6W in combination with atezolizumab at 1200 mg Q3W. Xilio is 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 are expected in the fourth quarter of 2024, with additional data in a total of approximately 40 patients expected in the first quarter of 2025.
