FDA Grants Orphan Drug Designation to Tovecimig for Biliary Tract Cancer

The FDA has granted orphan drug designation to tovecimig (CTX-009) for the treatment of patients with bile duct cancer, according to a press release from ABL Bio.¹ The decision follows previous regulatory milestones, such as fast track designation and orphan drug designation, for the bispecific antibody, which targets the DLL4 and VEGF-A signaling pathways to inhibit tumor angiogenesis and vascularization.

What are the efficacy findings for tovecimig in biliary tract cancer?

The most recent efficacy data for tovecimig comes from the phase 2/3 COMPANION-002 trial (NCT05506943), which evaluated the agent in combination with paclitaxel for patients with advanced disease.² Topline results demonstrated a statistically significant improvement in the primary end point of overall response rate (ORR) compared with paclitaxel monotherapy. In the combination arm, the ORR was 17.1% compared with 5.3% in the control arm (P = .031).

Among those receiving the tovecimig combination, 1 patient achieved a complete response and 16.2% achieved a partial response. Conversely, the control arm yielded no complete responses and a partial response rate of 5.3%. The study also reported a notable difference in progressive disease rates, with 16.2% observed in the tovecimig group vs 42.1% in the paclitaxel-alone group.

Secondary end points, including progression-free survival (PFS) and overall survival (OS), had not reached maturity at the time of the initial report. The developers now plan to release PFS and OS data later in April 2026.

“Compass Therapeutics received fast track designation from the FDA for tovecimig in April 2024. The company has been leveraging the benefits of this program in its clinical development,” said Lee Sang-hoon, chief executive officer of ABL Bio, in the press release.¹ “Compass Therapeutics plans to discuss future development stages with the FDA, based on clinical data from COMPANION-002. We expect this orphan drug designation, along with the fast track designation, will have a positive impact on the approval process for tovecimig.”

How is the phase 2/3 COMPANION-002 trial designed?

The COMPANION-002 trial is a multicenter, randomized, open-label study that enrolled 168 patients with unresectable advanced, metastatic, or recurrent biliary tract cancer. Patients were required to be at least 18 years of age with histologically or cytologically confirmed disease and documented progression following first-line therapy with gemcitabine and platinum-based chemotherapy.³ Participants also needed an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST v1.1, and an estimated life expectancy of at least 12 weeks.

Investigators randomly assigned patients in a 2:1 ratio to receive either the combination of tovecimig and paclitaxel (n = 111) or paclitaxel monotherapy (n = 57). The treatment regimen for the combination arm consisted of 10 mg/kg of tovecimig administered intravenously on days 1 and 15 of each 28-day cycle, alongside 80 mg/m² of intravenous paclitaxel on days 1, 8, and 15. The control arm received the same paclitaxel regimen. Patients in the monotherapy group were permitted to cross over to the tovecimig arm upon centrally confirmed disease progression.

The primary end point of the trial was ORR per independent central radiology review. Secondary end points included PFS, OS, and duration of response.

What is the safety and regulatory status of tovecimig?

The safety profile of tovecimig was manageable and consistent with prior clinical evaluations of the agent. As of the previous announcement of results in April 2025, an independent data monitoring committee had reviewed the safety data on 4 occasions and recommended the continuation of the trial without modification.

This orphan drug designation follows a prior regulatory decision by the FDA to grant fast track designation to tovecimig in April 2024 for the treatment of metastatic or locally advanced biliary tract cancers in the second-line setting.

References

1. ABL Bio's US partner wins FDA's orphan drug designation for bile duct cancer drug tovecimig. News release. Korea Biomedical Review. April 8, 2026. Accessed April 8, 2026. https://tinyurl.com/3nvv425s
2. Tovecimig (CTX-009) meets primary endpoint in the ongoing randomized phase 2/3 study in patients with biliary tract cancer. News release. Compass Therapeutics. April 1, 2025. Accessed April 8, 2026. https://tinyurl.com/3d7ry9fw
3. A study of CTX-009 in combination with paclitaxel in adult patients with unresectable advanced, metastatic or recurrent biliary tract cancers (COMPANION-002). ClinicalTrials.gov. Updated April 20, 2025. Accessed April 8, 2026. https://tinyurl.com/37wnbxxs