Tovecimig Yields Significant Responses in Advanced Biliary Tract Cancer

Tovecimig was developed as a bispecific antibody intended to block DLL4 and VEGF-A signaling pathways critical to angiogenesis and tumor vascularization.

Tovecimig (CTX-009) plus paclitaxel met the primary end point of overall response rate (ORR) in patients with advanced biliary tract cancer in the phase 2/3 COMPANION-002 trial (NCT05506943), according to a news release from the drug’s developer, Compass Therapeutics.¹

Findings from the study revealed that the tovecimig combination elicited an ORR of 17.1%, which included 1 complete response, compared with 5.3% with paclitaxel alone for patients with biliary tract cancer treated in the second-line setting. The ORR difference was statistically significant between the 2 arms (P = .031), and all responses have been confirmed by blinded independent central radiology review.

Additionally, progressive disease rates in the combination and paclitaxel alone groups were 16.2% and 42.1%, respectively. Additionally, the prespecified threshold of events in 80% of patients required to undergo analyses of the secondary end points, including progression-free survival, overall survival, and duration of response, have not been met. Compass Therapeutics expects to report these end points during the fourth quarter of 2025.

“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 the press 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.”

Patients with unresectable advanced, metastatic, or recurrent biliary tract cancers were randomly assigned 2:1 to receive either tovecimig plus paclitaxel (n = 111) or paclitaxel alone (n = 57). Patients received 80 mg/m² of intravenous paclitaxel on days 1, 8, and 15 of 28-day cycles.² Tovecimig was given at 10 mg/kg intravenously on days 1 and 15 of each 28-day cycle.

Patients in the paclitaxel arm could cross over to the tovecimig arm in the event of centrally confirmed disease progression assuming they still met enrollment criteria. Secondary end points included disease control rate, safety, and patient-reported quality of life.

The safety profile of tovecimig in the phase 2/3 COMPANION-002 trial was consistent with prior studies evaluating the agent. An independent data monitoring committee reviewed safety data at 4 meetings, recommending the continuation of study protocol without modification after each.

Tovecimig was developed as a bispecific antibody intended to block DLL4 and VEGF-A signaling pathways critical to angiogenesis and tumor vascularization.

"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."

Those eligible for enrollment included patients who were 18 years or older with histologically or cytologically confirmed unresectable advanced, metastatic, or recurrent biliary tract cancers; documented progression after prior gemcitabine and platinum-containing chemotherapy as a first-line therapy; at least 1 measurable lesion per RECIST v1.1 guidelines; and an ECOG performance status of 0 to 1.

References

1. 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 4, 2025. https://tinyurl.com/3d7ry9fw
2. 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 August 14, 2024. Accessed April 4, 2025. https://tinyurl.com/5h8jz2d9