On December 7, 2023 Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, reported 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 (IO) refractory solid tumors (Press release, Xilio Therapeutics, DEC 7, 2023, View Source [SID1234638260]). The data were presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Immuno-Oncology Congress on December 7, 2023.

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"With the recent initiation of Phase 1 dose escalation for XTX101 in combination with atezolizumab, we look forward to establishing a recommended Phase 2 dose in support of our plans to evaluate the combination in a Phase 2 trial in patients with microsatellite stable colorectal cancer (MSS CRC), including patients with liver metastases where there is an especially significant unmet need," said Katarina Luptakova, M.D., chief medical officer of Xilio. "The new Phase 1 data we reported for XTX101, which include 18 patients treated at the recommended Phase 2 dose of 150 mg Q6W, continue to demonstrate XTX101’s promising safety profile with primarily Grade 1 or 2 treatment-related adverse events. In addition to the previously reported confirmed partial response in a non-small cell lung cancer patient through 36 weeks, these new data also suggest further evidence of monotherapy anti-tumor activity in late-line and IO refractory patients at the recommended Phase 2 dose."

Updated Data from the Ongoing Phase 1 Clinical Trial for XTX101

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 (RP2D) of 150 mg once every six weeks (Q6W).

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 (including 9 patients previously reported) 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 (TRAE) 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 (≥10% incidence) reported by investigators was fatigue (11%).
● 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 (PR) was observed in a patient with Stage 4 PD-L1 negative non-small cell lung cancer (NSCLC), 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 (DCR) 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 (triple-negative breast cancer, melanoma and microsatellite stable colorectal cancer (n=1 each)).

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.

Poster Presentation

A copy of Xilio’s data presentation from the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress for XTX101 is available in the "Our Approach—Publications and Presentations" section of the company’s website at www.xiliotx.com.

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

About XTX101 (anti-CTLA-4) and the Phase 1 Monotherapy and Phase 1/2 Combination Clinical Trials

XTX101 is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to block CTLA-4 and deplete regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX101 for the treatment of adult patients with advanced solid tumors. Xilio has completed enrollment in monotherapy dose escalation (Part 1A) and monotherapy dose expansion (Part 1B). Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.

Xilio is currently evaluating the safety and tolerability of XTX101 in combination with atezolizumab (Tecentriq) in Phase 1 dose escalation in patients with advanced solid tumors, and subject to obtaining additional capital and the results of Phase 1 combination dose escalation, Xilio plans to evaluate the safety and efficacy of the combination in a Phase 2 trial in patients with microsatellite stable colorectal cancer (MSS CRC).