8-K: Xilio Therapeutics' Drug Shows Promise in Treating Advanced Colorectal Cancer in Phase 2 Trial

Xilio Therapeutics announced positive initial results from a Phase 2 trial of its tumor-activated drug, vilastobart, combined with atezolizumab, showing a 27% preliminary response rate in patients with advanced microsatellite stable colorectal cancer.

Summary

• Xilio Therapeutics reported initial data from its Phase 2 trial of vilastobart (XTX101) in combination with atezolizumab for treating metastatic microsatellite stable colorectal cancer (MSS CRC).
• The trial involved 40 heavily pre-treated patients, with 70% having received three or more prior lines of treatment.
• In patients without liver metastases, a preliminary objective response rate (ORR) of 27% was observed, including three partial responses (PRs), two of which were confirmed.
• These responses were accompanied by decreases in carcinoembryonic antigen (CEA) and circulating tumor DNA (ctDNA), along with improvements in clinical symptoms.
• As of the data cutoff date, 23 patients remained on treatment, with 13 yet to undergo their first response assessment.
• The combination therapy was generally well-tolerated, with a low incidence of immune-related adverse events.
• Only six patients experienced Grade 3 or 4 treatment-related adverse events, and no Grade 5 events were reported.
• Xilio plans to release updated data in mid-2025 and seek partnerships for further development of vilastobart.

Sentiment

Score: 8

Explanation: The sentiment is highly positive due to the promising efficacy data and well-tolerated safety profile, indicating potential for a new treatment option in a challenging indication.

Positives

• Promising efficacy with a 27% preliminary ORR in a heavily pre-treated patient population.
• Confirmed partial responses show significant tumor reduction (47% and 57% in two patients).
• Decreases in tumor biomarkers CEA and ctDNA indicate positive treatment response.
• Well-tolerated safety profile with low incidence of severe adverse events.
• No Grade 5 treatment-related adverse events were reported.
• Data supports the potential for vilastobart in combination with PD-(L)1 inhibitors in MSS CRC and other tumor types.

Negatives

• The trial is still ongoing, and the results are preliminary.
• Efficacy in patients with liver metastases was lower, with a 14% disease control rate.
• 8 patients discontinued treatment due to clinical progression.
• 3 patients discontinued treatment due to adverse events.

Risks

• The preliminary data may not be replicated in future clinical data or results.
• Regulatory agencies' actions may affect the initiation, timing, and progress of current or future clinical trials.
• The company may face challenges in obtaining and maintaining sufficient cash resources to fund its operations.
• International trade policies, including U.S. and China trade policies, could impact the company's business.
• The company may face difficulties in maintaining its clinical trial collaboration with Roche and its license agreement with Gilead.

Future Outlook

Xilio expects to report updated data from the Phase 2 trial in mid-2025 and plans to seek partnerships for further development of vilastobart beyond the initial Phase 2 trial.

Management Comments

• 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.'

Industry Context

The announcement relates to the broader trend of developing immuno-oncology therapies for solid tumors, particularly in indications like MSS CRC where current immunotherapies have shown limited efficacy.

Comparison to Industry Standards

• Immune checkpoint inhibitors like pembrolizumab and nivolumab have shown no meaningful efficacy in MSS CRC patients, with objective response rates (ORR) ranging from 0-3%.
• Xilio's reported 27% preliminary ORR in MSS CRC patients without liver metastases is significantly higher than the 0-3% ORR seen with existing immune checkpoint inhibitors in this patient population.
• Standard treatments for advanced MSS CRC typically include chemotherapy +/tyrosine kinase inhibitors (TKIs), followed by clinical trials or late-line therapies with minimal benefit, resulting in an overall survival (OS) of approximately 6-9 months.
• In comparison, Xilio's combination therapy has demonstrated promising early results with a 27% ORR and notable reductions in tumor biomarkers, suggesting a potential for improved outcomes compared to current standards.
• Other companies like Bristol Myers Squibb (Opdivo + Yervoy) and Merck (Keytruda) have explored combination therapies in MSS CRC but have not reported significant improvements in ORR for this patient population.

Stakeholder Impact

• Shareholders: Potential positive impact due to promising clinical data and future development plans.
• Employees: Continued focus on research and development, potentially leading to new opportunities.
• Patients: Potential for a new and effective treatment option for MSS CRC and other solid tumors.
• Suppliers: Increased demand for clinical trial supplies and related services.
• Creditors: Positive outlook for the company's financial stability based on promising clinical data.

Next Steps

• Report updated data from the Phase 2 trial in mid-2025.
• Seek opportunities for partnering to prioritize and expand further development of vilastobart.
• Continue enrolling patients in Phase 1C dose escalation and evaluate the combination of vilastobart and atezolizumab.

Key Dates

Keywords

Colorectal Cancer, MSS CRC, Immunotherapy, Tumor-Activated, CTLA-4, PD-L1, Vilastobart, XTX101, Atezolizumab, Clinical Trial, Phase 2, Biotechnology, Oncology