Xilio Therapeutics initiates enrollment for Phase 1 combination trial of XTX101

Xilio Therapeutics announced the initiation of enrollment for its Phase 1 clinical trial of XTX101, an investigational tumor-activated, Fc-enhanced anti-CTLA-4, in combination with atezolizumab and reported updated monotherapy data from its ongoing Phase 1 clinical trial evaluating XTX101 in late-line patients with advanced and immuno-oncology refractory solid tumors. The data were presented at the European Society for Medical Oncology Immuno-Oncology Congress on December 7, 2023. Update from ongoing Phase 1: As of the data cutoff date of November 13, 2023, 36 patients with advanced solid tumors had been administered XTX101 monotherapy, including 18 patients at the recommended Phase 2 dose and schedule of 150 mg once every six weeks. Patients treated at the RP2D of 150 mg Q6W were heavily pre-treated, with 83% of patients receiving three or more lines of anti-cancer therapy and 56% previously treated with an immunotherapy. Preliminary Safety Data At the RP2D of 150 mg Q6W, 18 patients were evaluable for safety as of the data cutoff date: Safety data were consistent with previously reported results. XTX101 monotherapy was generally well-tolerated with treatment-related adverse events primarily Grade 1 or 2, and no patients discontinued treatment due to a TRAE. In addition, as previously reported, only one patient had a dose reduction due to an adverse event. The most common TRAE of any grade reported by investigators was fatigue. As previously reported, investigators reported only two Grade 3 TRAEs: Grade 3 TRAE of diarrhea, which occurred after two doses and resolved after five days without steroid use, and one Grade 3 TRAE of dermatitis. In addition, as previously reported, no Grade 4 or 5 TRAEs were reported by investigators across all dosing levels and dosing intervals. Preliminary Anti-Tumor Activity Data At the RP2D of 150 mg Q6W, 12 patients were evaluable for anti-tumor activity as of the data cutoff date: As previously reported, a confirmed partial response was observed in a patient with Stage 4 PD-L1 negative non-small cell lung cancer, including complete resolution of liver metastases. The confirmed PR continued through 36 weeks of treatment with XTX101, with the patient discontinuing treatment after week 36 due to an unrelated adverse event. Additional data reported today demonstrated a disease control rate of 33% in late-line and IO refractory patients administered XTX101 monotherapy at the RP2D of 150 mg Q6W, consisting of the confirmed PR in the NSCLC patient and stable disease in three patients. Preliminary Pharmacokinetic Data: As previously reported, consistent with the tumor-selective design for XTX101, preliminary pharmacokinetic analyses demonstrated 96% activation of XTX101 in a melanoma tumor and 73% activation in a metastatic liver lesion in a colorectal cancer patient, compared to minimal peripheral activation of XTX101 of 13% in both patients. Clinical Development Plans for XTX101: Xilio recently completed enrolling patients at the RP2D of 150 mg Q6W in monotherapy dose expansion and initiated enrollment in Phase 1 combination dose escalation to evaluate the safety, tolerability and efficacy of XTX101 in combination with atezolizumab. As previously reported, subject to obtaining sufficient additional capital, Xilio plans to: Complete Phase 1 combination dose escalation and select a RP2D for XTX101 in combination with atezolizumab in the second quarter of 2024 Subject to the results of Phase 1 combination dose escalation, initiate a Phase 2 trial to evaluate the safety and efficacy of XTX101 in combination with atezolizumab in patients with MSS CRC in the third quarter of 2024