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 biliary tract cancer (BTC) according to Compass Therapeutics, the company developing the investigational bispecific antibody.¹

The designation is supported by data from the phase 2/3 COMPANION-002 trial (NCT05506943). Previously reported findings from the trial showed that adding tovecimig to paclitaxel significantly improved overall response rate (ORR) vs paclitaxel monotherapy in patients with advanced biliary tract cancer.² 

“As a treating clinician for over 20 years, I have seen firsthand how challenging a disease biliary tract cancer is. Patients currently have limited treatment options, with the vast majority in the second-line setting having no approved therapeutic alternative whatsoever,” Juan Valle, MD, chief medical officer of the Cholangiocarcinoma Foundation, stated in a news release.¹ “For every statistic, there is a person—a mother, father, relative, or friend—fighting for more time. Each investigative trial helps in this fight to advance new treatment options, and I look forward to following tovecimig’s continued progress.”

COMPANION-002 Trial

Tovecimig simultaneously inhibits 2 pathways central to tumor angiogenesis, DLL4 and VEGF-A with preclinical and clinical data suggesting that dual blockade produces greater antitumor activity than inhibition of either pathway alone, including in VEGF-resistant settings.

The ongoing phase 2/3 COMPANION-002 trial is randomizing patients with second-line advanced BTC who have progressed on gemcitabine and platinum-based chemotherapy to tovecimig plus paclitaxel versus paclitaxel alone. The trial enrolled patients regardless of biomarker status, making the results broadly applicable to the population seen in community practice.

Topline data announced in April 2025 demonstrated a statistically significant improvement in the primary endpoint of ORR: 17.1% for the combination versus 5.3% for paclitaxel alone (P =.031), with all responses confirmed by blinded independent central radiology review. Progressive disease rates were notably lower in the combination arm as well. 16.2% vs 42.1% in the control arm, suggesting meaningful disease control beyond response alone.² 

To qualify for enrollment, patients were required to be at least 18 years of age with histologically or cytologically confirmed disease—specifically unresectable advanced, metastatic, or recurrent biliary tract cancer. Additional eligibility requirements included documented disease progression following first-line gemcitabine- and platinum-based chemotherapy, a minimum of one measurable lesion meeting RECIST v1.1 criteria, and an ECOG performance status of 0 or 1.

Enrolled patients were randomized in a 2:1 ratio to receive either the combination of tovecimig plus paclitaxel (n = 111) or paclitaxel as a single agent (n = 57). Paclitaxel was delivered intravenously at 80 mg/m² on days 1, 8, and 15 of each 28-day cycle, while tovecimig was administered intravenously at 10 mg/kg on days 1 and 15 of the same cycle schedule.²

Participants originally assigned to paclitaxel monotherapy were permitted to cross over to the tovecimig-containing arm upon centrally confirmed disease progression, provided they continued to satisfy the original enrollment criteria. Among the trial's secondary end points were disease control rate, tolerability, and health-related quality of life as reported by patients.

The safety findings from COMPANION-002 were in line with what had previously been observed in earlier studies of tovecimig, with no new or unexpected safety signals identified. An independent data monitoring committee convened across four separate meetings to review accumulating safety data and concluded each time that the study protocol should proceed without modification.

"We are thrilled to share these positive primary end point data from the COMPANION-002 study of tovecimig in patients with advanced biliary tract cancer," Thomas Schuetz, MD, PhD, CEO of Compass and vice chairman of their board of directors, said in the news release.¹ “We would like to thank all the patients and their caregivers who have participated and continue to participate in this study. We believe these findings highlight the potential of tovecimig to provide a much-needed treatment option for the majority of patients with biliary tract cancer who have limited alternatives after first-line therapy. We look forward to discussing these data with regulatory authorities."

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