Parabilis Reports 100% Disease Control With Zolucatetide in Desmoid Tumors

Parabilis Medicines presented updated Phase 1/2 data for investigational zolucatetide (FOG-001) in patients with desmoid tumors at the European Society for Medical Oncology (ESMO) Congress 2026 on October 24. Based on a June 22, 2026, data cutoff, the findings support continued development of the oral therapy, while the limited number of patients evaluable at 32 weeks remains an important consideration.

Updated Results Show Tumor Responses

Among patients who began treatment at a starting dose of at least 450 mg, the objective response rate (ORR), assessed using RECIST 1.1, was 72.2% (13/18) among those evaluable at the 32-week landmark. The disease control rate (DCR) was 100% among 46 response-evaluable patients in the same starting-dose cohort, with no disease progression reported.

These results suggest antitumor activity in desmoid tumors, which can be locally invasive and recurrent. However, the two efficacy measures describe different populations. The ORR reflects 18 patients with scans available at Week 32, whereas the DCR covers 46 response-evaluable patients. The results should therefore not be interpreted as equivalent estimates of efficacy or as evidence of durable disease control.

Patient Population and Treatment Exposure

As of the data cutoff, 76 patients with desmoid tumors had received zolucatetide across all dose levels. The median age was 37 years (range 19–80), and 69.7% were female. The population included patients previously treated with and failing gamma-secretase inhibitors (GSIs), as well as GSI-naive patients.

Of the 76 patients, 48 began treatment at a starting induction dose of at least 450 mg before transitioning to maintenance dosing. Two patients started at 900 mg but received an average dose of 400–500 mg during the first four months. Of the 48 patients, 46 were response-evaluable and 18 had scans at Week 32. Median treatment duration in this cohort was 4.7 months (range 0.5–22.3), reflecting the recent enrollment of many participants.

Parabilis reported responses regardless of prior GSI exposure or CTNNB1 or APC mutation status. These findings are relevant because alterations involving these genes can activate Wnt/β-catenin signaling. However, the announcement does not provide subgroup-specific response rates or confidence intervals, preventing a robust comparison of activity across molecular and treatment subgroups.

Safety Findings and Phase 3 Development

Treatment-related adverse events (TRAEs) were predominantly low-grade, with fatigue, alopecia and nausea among the most frequently reported. No patients discontinued treatment because of TRAEs. The company also reported no ovarian toxicity or high-grade gastrointestinal or skin toxicities commonly associated with GSIs.

These observations are encouraging for a disease that may require prolonged treatment. Nevertheless, the absence of treatment discontinuations does not establish long-term tolerability. Detailed adverse-event incidence rates and longer-term safety data remain necessary to characterize the treatment’s risk profile.

A three-arm randomized dose-optimization study informed selection of a regimen comprising 450 mg weekly for four induction cycles, followed by 300 mg every two weeks for maintenance. Following end-of-Phase 2 discussions, Parabilis reported alignment with the U.S. Food and Drug Administration (FDA) on the selected dose and regimen, a placebo-controlled study design, and progression-free survival (PFS) as the primary endpoint for registrational development.

The planned PEDESTAL Phase 3 trial is a randomized, double-blind, placebo-controlled study expected to begin in the first half of 2027, with topline results anticipated in 2029. Zolucatetide has received FDA Fast Track and Orphan Drug designations for desmoid tumors. These regulatory designations and development discussions do not constitute marketing approval or establish clinical benefit.

Clinical Interpretation

Zolucatetide is designed to inhibit the β-catenin interaction, a downstream component of Wnt/β-catenin signaling. The reported 72.2% ORR at 32 weeks and 100% DCR among 46 response-evaluable patients provide a preliminary clinical signal supporting further investigation.

However, the landmark response estimate is based on only 18 patients, follow-up varies, and detailed response-duration data and confidence intervals were not provided in the announcement. The reported absence of progression in the evaluable cohort should not be interpreted as proof of durable disease control or as evidence that acquired resistance cannot occur.

The planned PEDESTAL trial will be important in determining whether zolucatetide improves PFS compared with placebo and whether the early response signal translates into a clinically meaningful, durable benefit. Until controlled data are available, zolucatetide remains investigational, and its efficacy and safety require further confirmation.

Reference

Parabilis Medicines Presents Updated Phase 1/2 Data for Zolucatetide Demonstrating Compelling Efficacy and Favorable Safety and Tolerability Profile in Patients with Desmoid Tumors, Parabilis Medicines,  October 24, 2026.

FOG-001 in Locally Advanced or Metastatic Solid Tumors, ClinicalTrials.gov ID NCT05919264