FDA recommends an overall survival trial before a tovecimig BLA in biliary tract cancer after COMPANION-002 showed significant ORR and PFS benefits.
Written By: Creola Gonsalves, MS Biotech
Reviewed By: Pharmacally Editorial Team
The U.S. Food and Drug Administration has recommended that Compass Therapeutics conduct a trial demonstrating an overall survival benefit before submitting a Biologics License Application for investigational tovecimig in previously treated, advanced biliary tract cancer. The recommendation follows Phase 2/3 COMPANION-002 results showing statistically significant improvements in objective response rate and progression-free survival, while overall survival did not reach statistical significance.
FDA Seeks Additional Survival Evidence
The FDA recommended an additional trial demonstrating a survival benefit before Compass proceeds with a BLA submission for tovecimig. Compass said it does not believe a new trial is warranted before submission, citing the efficacy demonstrated in COMPANION-002 and the urgent need for new treatment options in previously treated biliary tract cancer.
The regulatory feedback creates a gap between the efficacy endpoints demonstrated in the trial and the level of evidence the FDA currently considers necessary to support a BLA. While COMPANION-002 showed significant improvements in ORR and PFS, it did not establish a statistically significant overall survival benefit.
Compass plans to continue discussions with the FDA while advancing preparations for its regulatory submission.
COMPANION-002 Demonstrated Significant ORR and PFS Benefits
The Phase 2/3 COMPANION-002 study evaluated tovecimig in combination with paclitaxel in patients with previously treated, advanced biliary tract cancer.
The study met its primary objective response rate endpoint. ORR was 18.0% with tovecimig plus paclitaxel compared with 5.3% with paclitaxel alone, a statistically significant difference (p=0.0228).
The combination also produced a significant progression-free survival benefit. Median PFS was 4.7 months versus 2.6 months with paclitaxel alone. The hazard ratio was 0.44 (p<0.0001), corresponding to a 56% relative reduction in the risk of disease progression or death.
These findings provide evidence of antitumor activity and improved disease control in a population with previously treated advanced biliary tract cancer.
Overall Survival Analysis Was Confounded by Crossover
Overall survival did not reach statistical significance in COMPANION-002. Compass attributed the result in part to substantial crossover from the paclitaxel control arm to tovecimig and prolonged survival among patients who subsequently received tovecimig.
Crossover can reduce the observed difference between randomized treatment groups and complicate interpretation of an unadjusted overall survival comparison. The company therefore highlighted subset survival analyses alongside the significant ORR and PFS findings when describing the overall clinical activity of tovecimig.
The reported safety profile remained generally consistent with previously reported tovecimig studies.
Tovecimig Blocks DLL4 and VEGF-A
Tovecimig is an investigational bispecific antibody targeting DLL4 and VEGF-A, two signaling pathways involved in tumor angiogenesis. Simultaneous blockade of these pathways is intended to interfere with mechanisms that support tumor blood-vessel formation and tumor growth.
The program has received Fast Track and Orphan Drug Designation from the FDA.
Biliary tract cancer comprises malignancies arising in the bile ducts and gallbladder and can progress rapidly. Treatment options become more limited after prior therapy, making additional systemic approaches an area of significant clinical need.
Compass Continues Regulatory Discussions
Thomas Schuetz, M.D., Ph.D., CEO of Compass Therapeutics, said the company respects the FDA’s feedback and will continue working with the agency to determine the appropriate path toward a BLA.
Compass remains confident in tovecimig based on the statistically significant ORR and PFS improvements observed in COMPANION-002, as well as its analyses of survival outcomes.
The next step will be further regulatory engagement with the FDA. The key question is whether the existing COMPANION-002 data can support a BLA submission or whether the agency will require additional clinical evidence demonstrating an overall survival benefit before the application can proceed.
Reference
Compass Therapeutics Provides Regulatory Update on Tovecimig in Biliary Tract Cancer Following FDA Feedback, Compass Therapeutics, 22 September 2026
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 ID NCT05506943
About the Writer
Creola Gonsalves (Linkedin) is an M.S. Biotechnology postgraduate with a strong interest in clinical research, evidence interpretation, and healthcare writing, with a focus on translating life-science knowledge into meaningful real-world insights.
She is trained in Good Clinical Practice (GCP), clinical research principles, and critical interpretation of randomized clinical trials, with certifications from NIH and Stanford University.
Her research background in biotechnological applications and microbial research strengthens her ability to understand scientific evidence and develop clear, accurate, and research-driven healthcare content.