Vilamakitug Meets Phase 2 Efficacy Criterion in Refractory Metastatic Colorectal Cancer

Vilamakitug (Natrunix; XB2001), an investigational anti-IL-1α monoclonal antibody, met the prespecified primary efficacy criterion in the phase 2 TASKIN trial (NCT05201352) in patients with refractory metastatic colorectal cancer (mCRC), according to final results announced by XBiotech. The findings support further investigation of vilamakitug in this population, particularly among patients with right-sided primary tumors.¹

TASKIN was an investigator-sponsored, randomized, double-blind, multicenter phase 2 study funded by the French National Cancer Institute and coordinated by investigators at Centre Georges-François Leclerc in Dijon, France. The trial evaluated vilamakitug in combination with trifluridine/tipiracil (Lonsurf), with or without bevacizumab (Avastin), compared with placebo plus standard-of-care treatment.

At the 12-month landmark analysis, 49 of 80 evaluable patients (61.3%) in the vilamakitug arm were alive compared with 44 of 79 patients (55.7%) in the control arm. The study met its prespecified efficacy criterion under a Simon 2-stage design, which required at least 42 surviving patients in the experimental arm to establish efficacy.

Other efficacy outcomes did not demonstrate statistically significant differences between treatment groups. Median progression-free survival was 5.9 months with vilamakitug compared with 5.6 months with placebo plus standard-of-care therapy, with no statistically significant difference between groups (P = .42). The 12-month time-to-strategy-failure rate was 31.2% with vilamakitug vs 20.3% with placebo, also without a statistically significant difference (P = .17).¹

Treatment options for refractory mCRC onceinclude trifluridine/tipiracil plus bevacizumab, fruquintinib (Fruzaqla), and regorafenib (Stivarga), with treatment selection influenced by prior therapies, tolerability, and patient-specific factors. In the phase 3 SUNLIGHT trial, trifluridine/tipiracil plus bevacizumab improved median overall survival to 10.8 months compared with 7.5 months with trifluridine/tipiracil alone, establishing the combination as an important option in this setting.² However, additional therapies remain needed for patients whose disease progresses despite available treatments.

Exploratory Findings in Right-Sided Tumors

An exploratory analysis of 37 patients with right-sided primary tumors suggested a potential survival benefit with vilamakitug. Patients receiving vilamakitug had a 62% lower estimated risk of death than those in the control group (HR, 0.38; 95% CI, 0.14-0.99; P = .047). Time to strategy failure also favored vilamakitug (HR, 0.39; 95% CI, 0.18-0.85; P = .014).¹

François Ghiringhelli, MD, PhD, principal investigator of TASKIN and director of the oncology department at Centre Georges-François Leclerc, said in the news release, “Most striking is the magnitude of benefit observed in right-sided colorectal cancers, which has been a historically aggressive disease subset with high unmet medical need.”

The investigators also reported that the apparent clinical benefit in right-sided tumors aligned with elevated baseline IL-1α tumor expression, providing a potential biological rationale for further study. However, the subgroup analysis was exploratory and included a limited number of patients.

Safety and Next Steps

Vilamakitug was administered with chemotherapy with a reported mean trifluridine/tipiracil compliance rate of 96.4%. Permanent discontinuation of vilamakitug or placebo occurred in 1.3% of patients.¹ The company did not provide detailed adverse event rates in the announcement.

XBiotech plans to advance vilamakitug toward registrational clinical development, with right-sided mCRC representing a potential focus for further investigation. “TASKIN provides a focused and validated direction as we advance vilamakitug toward registrational clinical development,” said Sushma Shivaswamy, PhD, chief scientific officer and interim CEO of XBiotech, in the news release. Additional clinical data will be needed to establish the treatment’s efficacy and safety and clarify its potential role alongside existing therapies for refractory mCRC.

REFERENCES

1. XBiotech announces positive phase II final efficacy results from investigator-sponsored TASKIN trial in refractory metastatic colorectal cancer. News release. BioSpace. October 19, 2026. Accessed October 19, 2026. https://tinyurl.com/ujyh2suc

2. FDA approves trifluridine and tipiracil with bevacizumab for previously treated metastatic colorectal cancer. News release. US FDA. August 2, 2023. Accessed October 19, 2026. https://tinyurl.com/3ep924mr