Xilio Therapeutics Announces Initial Phase 2 Data for Vilastobart (XTX101), a Tumor-Activated Anti-CTLA-4, in Combination with Atezolizumab in Patients with Metastatic Microsatellite Stable Colorectal Cancer

27% preliminary response rate observed in heavily pre-treated microsatellite stable colorectal cancer (MSS CRC) patients without liver metastases

Responses were accompanied by decreases in levels of carcinoembryonic antigen (CEA) and circulating tumor DNA (ctDNA) and improvement in clinical symptoms

Data continue to demonstrate differentiated safety and tolerability profile for the combination with low incidence of immune-related adverse events

Xilio Therapeutics to host investor conference call and webcast on Wednesday, January 22, 2025, at 8:30 am ET

WALTHAM, Mass., Jan. 21, 2025 (GLOBE NEWSWIRE) -- Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, today announced initial data from its ongoing Phase 2 clinical trial evaluating vilastobart (XTX101), a tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4, in combination with atezolizumab (Tecentriq®) in patients with metastatic microsatellite stable colorectal cancer (MSS CRC). The data will be presented in a poster session (abstract #206) at the American Society of Clinical Oncology 2025 Gastrointestinal Cancer Symposium (ASCO GI) being held January 23-25, 2025, in San Francisco.

“We are very encouraged by the initial Phase 2 proof-of-concept data for the combination of vilastobart and atezolizumab in heavily pre-treated patients with MSS colorectal cancer, including partial responses accompanied by marked decreases in tumor biomarkers and improvement in clinical symptoms,” said Katarina Luptakova, M.D., chief medical officer of Xilio. “We believe these data highlight the important contribution of vilastobart in this combination, as PD-(L)1 inhibitors alone have demonstrated no meaningful efficacy in patients with MSS CRC to date. The preliminary evidence of anti-tumor activity, together with continued evidence of a well-tolerated safety profile, support the potential for the combination in MSS colorectal cancer, as well as in other tumors that have traditionally been resistant to treatment with immunotherapy. We look forward to sharing additional Phase 2 data, including further follow-up, in patients with metastatic MSS CRC in the middle of this year.”

“These preliminary Phase 2 data for the combination of vilastobart and atezolizumab show clear responses for patients with MSS colorectal cancer, an area of very high and increasing unmet medical need,” said J. Randolph Hecht, M.D., Professor of Clinical Medicine at the David Geffen School of Medicine at UCLA, Director of the UCLA Gastrointestinal Oncology Program and the lead author for the presentation at ASCO GI. “I am excited to see these initial data highlighting the potential for vilastobart, a tumor-activated anti-CTLA-4, in combination with PD-(L)1 inhibitors to have clinically meaningful benefit in a classically immunotherapy-resistant major malignancy.”

Data from Phase 2 Trial for Vilastobart (XTX101), a Tumor-Activated Anti-CTLA-4, in Combination with Atezolizumab in Patients with Metastatic MSS CRC

As of a data cutoff date of January 13, 2025, 40 patients with metastatic MSS CRC had been treated with the combination of vilastobart at a dose of 100 mg once every six weeks (Q6W) and atezolizumab at 1200 mg once every three weeks (Q3W). The median age was 55 years (ranging from 25 to 82 years), and patients were heavily pre-treated, with 70% of patients having previously received three or more prior lines of anti-cancer therapy.

Preliminary Anti-Tumor Activity Data

In patients without liver metastases, the preliminary objective response rate (ORR) was 27% with three partial responses (PRs), including two confirmed PRs. Responses were accompanied by decreases in levels of carcinoembryonic antigen (CEA) and circulating tumor DNA (ctDNA) as well as improvement in clinical symptoms.

As of the data cutoff date, 18 patients had at least one imaging scan reported and were evaluable for response assessment (per RECIST version 1.1 criteria), including 11 patients without liver metastases and seven patients with liver metastases.

In response-evaluable MSS CRC patients without liver metastases, investigators reported three PRs (two confirmed, one pending confirmation), with each patient ongoing on treatment as of the data cutoff date:

• PR (confirmed) with a 47% decrease in the sum of diameters of target lesions at 13 weeks accompanied by a decrease in levels of the serum tumor marker CEA, a multi-log fold decrease in levels of ctDNA and improvement of clinical symptoms, such as cough. CEA is a serum biomarker that is often elevated in many malignancies, including colorectal cancer, and ctDNA is a biomarker found in the bloodstream of patients with cancer.
• PR (confirmed) that continued to deepen over time with a 57% reduction in the sum of diameters of target lesions at 18 weeks accompanied by a multi-log fold decrease in ctDNA to undetectable levels and significant decrease in levels of the serum tumor marker CEA to normal values.
• PR (pending confirmation) with a 35% decrease in the sum of diameters of target lesions at nine weeks accompanied by a decrease in levels of the tumor marker CEA to normal values, a substantial decrease in levels of ctDNA and improvement of clinical symptoms, such as cough. For this patient, the initial response on CT imaging was assessed by the investigator and the radiology assessment is pending.

In addition, an MSS CRC patient without liver metastases but with a peritoneal metastasis had a 24% decrease in the sum of diameters of target lesions assessed by CT imaging at their initial nine-week scan accompanied by a decrease in levels of the serum tumor marker CEA to normal values. This patient was ongoing on treatment as of the data cutoff date.

Investigators reported stable disease in three patients without liver metastases and one patient with liver metastases, representing a preliminary disease control rate of 55% and 14%, respectively, and highlighting additional evidence of anti-tumor activity for the combination.

As of the data cutoff date, 23 patients were ongoing on treatment, including 13 patients who had not yet had a first response assessment.

Preliminary Safety Data

Safety data continue to support the potential for vilastobart to be a differentiated next-generation anti-CTLA-4 in combination with PD-(L)1 inhibitors. Consistent with the tumor-selective design for vilastobart, the combination was generally well-tolerated, with patients experiencing a low incidence of immune-related adverse events (irAEs) and only 5% of patients reporting colitis.

As of the data cutoff date, 40 patients were evaluable for safety. Across all patients treated:

• Investigators reported only six patients with Grade 3 or 4 treatment-related adverse events (AEs), including only two Grade 4 treatment-related AEs (laboratory abnormalities of thrombocytopenia and neutropenia, one patient each), and no Grade 5 treatment-related AEs.
• No patients experienced a dose reduction for vilastobart due to an AE, and only three patients discontinued treatment for the combination of vilastobart and atezolizumab due to a treatment-related AE.
• Investigators reported minimal endocrine irAEs (5%) and limited skin irAEs (13%), and the incidence of endocrine and skin irAEs was consistent with the incidence reported for atezolizumab alone.
• The most common treatment-related AEs (≥10% incidence) of any grade reported by investigators were the following: fatigue (30%); diarrhea (20%); infusion-related reactions (13%, with 8% deemed related to vilastobart and 5% deemed related to atezolizumab); pyrexia (10%); aspartate aminotransferase (AST) increase (10%); and alanine aminotransferase (ALT) increase (10%).
• The only Grade 3 treatment-related AE with ≥5% incidence reported by investigators was colitis (5%). Non-laboratory Grade 3 treatment-related AEs (