Vilamakitug Meets OS Threshold in Phase 1/2 Refractory mCRC Trial

Adding vilamakitug (XB2001), a monoclonal antibody directed against interleukin-1α (IL-1α), to standard-of-care trifluridine/tipiracil (Lonsurf) with or without bevacizumab (Avastin) met a prespecified 12-month overall survival (OS) criterion in patients with refractory metastatic colorectal cancer (mCRC) in the randomized phase 1/2 TASKIN trial (NCT05201352).¹

At 12 months, 49 of 80 patients (61.3%) in the vilamakitug arm were alive vs 44 of 79 patients (55.7%) in the placebo arm, against a protocol threshold of at least 42 survivors.The 12-month time to strategy failure (TSF) rates were 31.2% vs 20.3%, respectively (log-rank P = .17), and the respective median progression-free survival (PFS) values were 5.9 months vs 5.6 months, with 12-month PFS rates of 25.0% vs 21.0%, respectively (log-rank P = .42). Notably, the survival curves visibly separated after 7 months.

TASKIN principal investigator François Ghiringhelli, MD, PhD, head of Oncology at Centre Georges-François Leclerc in Dijon, France, said the trial met its prespecified primary milestone.

How was the TASKIN trial designed?

The TASKIN investigators hypothesized, on the basis of earlier interleukin-1 (IL-1) inhibition trials and preclinical data, that IL-1 inhibition may increase the efficacy of trifluridine/tipiracil.²

TASKIN is a multicenter trial. The phase 1 portion evaluated safety and set the dose that was carried into phase 2. The double-blind phase 2 portion randomly assigned patients 1:1 to receive vilamakitug or placebo plus standard trifluridine/tipiracil, used a Simon 2-stage design, and continued dosing until disease progression or unacceptable adverse effects.¹

Enrollment required patients to be 18 years or older with an ECOG performance status of 0 or 1 and histologically confirmed mCRC with prior exposure to oxaliplatin, irinotecan, a fluoropyrimidine, and anti-VEGF therapy, plus anti-EGFR therapy when indicated.² Tumors with microsatellite instability were allowed after prior PD-1 or PD-L1 inhibitor therapy, measurable disease per RECIST 1.1 criteria was required, and patients with BRAF V600E–mutant tumors were excluded.

TASKIN has a planned enrollment of 160 patients. The trial was initiated on October 13, 2022. To date, 80 evaluable patients have been enrolled in the vilamakitug arm, and 79 evaluable patients have been enrolled in the control arm.¹

What efficacy findings were reported beyond 12-month OS?

The mean compliance rate with trifluridine/tipiracil was 96.4%, and permanent discontinuation of vilamakitug or placebo occurred in 1.3% of patients.

What did the exploratory analysis of right-sided primary tumors show?

In a prospective, exploratory analysis of patients with right-sided (proximal) primary tumors (n = 37), vilamakitug-based therapy led to a 62% reduction in the risk of death compared with control (HR for OS through 12 months, 0.38; 95% CI, 0.14-0.99; Cox P = .047; log-rank P = .038). Vilamakitug-based therapy also led to a 61% reduction in the risk of strategy failure (HR for TSF, 0.39; 95% CI, 0.18-0.85; Cox P = .017; log-rank P = .014).

How does research with vilamakitug fit into the broader mCRC treatment landscape?

“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,” Sushma Shivaswamy, PhD, chief scientific officer and interim chief executive officer of XBiotech, stated in a news release.

Other agents in the refractory mCRC setting have drawn regulatory activity this month as well. The FDA granted breakthrough therapy designation to telisotuzumab adizutecan plus bevacizumab for the treatment of patients with mCRC previously treated with fluoropyrimidine, irinotecan, oxaliplatin, and anti-VEGF therapy.³ Additionally, Armenia granted conditional marketing authorizations to botensilimab (Botvymo) plus balstilimab (Evamplix) for the treatment of patients with previously treated microsatellite-stable mCRC without active liver metastases.⁴

References

1. XBiotech announces positive phase II final efficacy results from investigator-sponsored TASKIN trial in refractory metastatic colorectal cancer. News release. XBiotech Inc. October 19, 2026. Accessed October 19, 2026. https://investors.xbiotech.com/news-releases/news-release-details/xbiotech-announces-positive-phase-ii-final-efficacy-results
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://clinicaltrials.gov/study/NCT05201352
3. AbbVie’s telisotuzumab adizutecan (Temab-A) receives two breakthrough therapy designations from the U.S. FDA for CRC and NSCLC. News release. AbbVie. October 7, 2026. Accessed October 19, 2026. https://news.abbvie.com/2026-10-07-AbbVies-Telisotuzumab-Adizutecan-Temab-A-Receives-Two-Breakthrough-Therapy-Designations-From-the-U-S-FDA-for-CRC-and-NSCLC
4. Agenus Inc. Armenia grants first marketing authorizations for Agenus’ BOT+BAL in previously treated MSS metastatic colorectal cancer. News release. October 8, 2026. Accessed October 19, 2026. https://investor.agenusbio.com/news/news-details/2026/Armenia-Grants-First-Marketing-Authorizations-for-Agenus-BOTBAL-in-Previously-Treated-MSS-Metastatic-Colorectal-Cancer/default.aspx