Vilamakitug Plus Chemo Meets Survival Threshold in Refractory Metastatic CRC

Vilamakitug (XB2001), an investigational anti–interleukin-1α (IL-1α) antibody, met its prespecified 12-month overall survival (OS) threshold when added to trifluridine/tipiracil (Lonsurf) in patients with refractory metastatic colorectal cancer (CRC) in the phase 2 TASKIN trial (NCT05201352), according to a news release from XBiotech.¹ An exploratory analysis also found a survival signal in patients with right-sided primary tumors.

What were the primary results from the TASKIN trial?

At 12 months, 49 of 80 patients (61.3%) in the vilamakitug arm were alive, compared with 44 of 79 (55.7%) in the control arm. The protocol-defined threshold to establish efficacy under a Simon two-stage design was 42 or more surviving patients.

Other end points did not differ significantly between arms in the overall population. Median progression-free survival (PFS) was 5.9 months with vilamakitug vs 5.6 months with control, and the 12-month PFS rate was 25.0% vs 21.0% (log-rank P = .42). The 12-month time to strategy failure rate was 31.2% vs 20.3% (log-rank P = .17).

Investigators noted that vilamakitug was feasible in combination with chemotherapy, as the mean compliance with trifluridine/tipiracil was 96.4%, and 1.3% of patients permanently discontinued vilamakitug or placebo.

What did the exploratory analysis show in right-sided tumors?

Among 37 patients with right-sided (proximal) primary tumors, vilamakitug was associated with a 62% reduction in the risk of death through 12 months (HR, 0.38; 95% CI, 0.14-0.99; Cox P = .047) and a 61% reduction in the risk of treatment strategy failure (HR, 0.39; 95% CI, 0.18-0.85; Cox P = .017).

Professor François Ghiringhelli, MD, PhD, the principal investigator of the TASKIN trial and director of the Oncology department at Centre Georges-François Leclerc (CGFL), said, “Patients with refractory metastatic colorectal cancer face severe therapeutic limitations and poor survival outcomes. Meeting our pre-specified primary milestone provides compelling evidence that targeting IL-1α plays a meaningful role in tumor biology. 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 alignment between this pronounced clinical survival advantage and elevated basal IL-1α tumor expression offers a clear biological rationale for this therapy.”¹

How was the TASKIN trial designed?

TASKIN is an investigator-sponsored trial funded by the French National Cancer Institute and sponsored by CGFL, with centers across France. The phase 1 portion established the safety and recommended phase 2 dose of vilamakitug. In the double-blind phase 2 portion, heavily pretreated patients with refractory metastatic CRC were randomized 1:1 to vilamakitug or placebo, each added to trifluridine/tipiracil with or without bevacizumab (Avastin).

Eligible patients were 18 years or older with an ECOG performance status of 0 or 1, had received prior oxaliplatin, irinotecan, and fluoropyrimidine-based therapy, and had measurable disease per RECIST 1.1.² Patients with BRAF V600E mutations or prior trifluridine/tipiracil were excluded.

Treatment in the experimental arm consisted of vilamakitug at 1000 mg via intravenous infusion every 2 weeks plus trifluridine/tipiracil every 28 days; in the control arm, vilamakitug was replaced with placebo.

What is vilamakitug?

Vilamakitug is a human monoclonal antibody derived from a donor with a natural immune response to IL-1α, a cytokine XBiotech said supports tumor growth.

“We are deeply grateful to Professor Ghiringhelli, the team at Centre Georges-François Leclerc, the French National Cancer Institute, and all the participating patients for advancing this important trial,” added Sushma Shivaswamy, PhD, chief scientific officer and interim chief executive officer of XBiotech, in the press release.¹ “By uncovering a biomarker-anchored patient population in right-sided disease that derives substantial clinical benefit from vilamakitug, TASKIN provides a focused and validated direction as we advance vilamakitug toward registrational clinical development.”

References

1. XBiotech announces positive phase II final efficacy results from investigator-sponsored TASKIN trial in refractory metastatic colorectal cancer. News release. XBiotech. October 19, 2026. Accessed October 19, 2026. https://tinyurl.com/49bnu9tw
2. Evaluation of efficacy of trifluridine/​tipiracil plus an anti-IL-1α true human antibody versus trifluridine/​tipiracil plus placebo in metastatic colorectal cancer patients after failure of oxaliplatin, irinotecan, fluoropyrimidine (TASKIN). ClinicalTrials.gov. Updated May 30, 2025. Accessed October 19, 2026. https://tinyurl.com/2fr55a54