Xilio Therapeutics, Inc. Announced preliminary dose-escalation data reported for XTX101, a tumor-selective anti-CTLA-4. These data provide initial clinical validation of Xilio's geographically precise solutions (GPS) platform and demonstrate that XTX101 has reached dose levels above the target dose with limited active (unmasked) molecule in peripheral circulation. Based on these data, the company plan to explore a Phase 2 clinical trial for XTX101 in microsatellite stable (MSS) colorectal cancer. XTX101: Preliminary Dose-Escalation Data from Ongoing Phase 1 Clinical Trial: XTX101, an Fc-enhanced, tumor-selective anti-CTLA-4, is being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors.

The target dose level for XTX101 of 60 mg is anticipated to provide anti-tumor activity similar to ipilimumab at 10 mg/kg (approximately 600 mg in a 60 kg patient) based on the 10 times greater potency observed for XTX101 relative to an ipilimumab analogue in preclinical studies. As of August 5, 2022, 12 patients have been treated with XTX101 in the monotherapy dose-escalation cohort (Part 1A) at four dose levels ranging from 7 mg to 180 mg: The 180 mg dose level has surpassed the 60 mg target dose level for XTX101. As a result, Xilio recently expanded enrollment at the 180 mg dose level.

A maximum tolerated dose (MTD) has not yet been determined, and enrollment in the dose-escalation cohort is ongoing. Preliminary pharmacokinetic (PK) analyses demonstrated dose-proportional drug exposure, with limited active (unmasked) XTX101 in peripheral circulation (range of % active in periphery: 6% - 16%) consistent with PK data observed in preclinical studies. Additional XTX101 Development Updates: Xilio recently opened Part 1B of the clinical trial for patient enrollment, which is a monotherapy cohort designed to evaluate anti-tumor activity, including intra-tumoral PK and pharmacodynamic (PD) data, in patients with anti-CTLA-4 sensitive tumor types, with the goal of characterizing the anti-tumor activity of XTX101 at one or more dose levels selected in Part 1A of the trial.

Given the potential for Fc-enhanced anti-CTLA-4 agents like XTX101 to demonstrate activity in tumors that are historically resistant to immuno-oncology treatment, Xilio plans to explore evaluating XTX101 in a Phase 2 clinical trial in patients with microsatellite stable (MSS) colorectal cancer in combination with an anti-PD(L)-1. XTX202: Phase 1 Clinical Trial Progress: XTX202, a tumor-selective, engineered IL-2, is being evaluated in a Phase 1 clinical trial in patients with advanced solid tumors. As of August 5, 2022, six patients have been treated with XTX202 as outpatients in the monotherapy dose-escalation cohort (Part 1A) at three dose levels ranging from 0.27 mg/kg to 0.53 mg/kg. An MTD has not yet been determined, and enrollment in the dose-escalation cohort is ongoing.