Tovecimig Submission for Biliary Cancer Proceeding Despite FDA Request for New Trial

The FDA has advised Compass Therapeutics to conduct a new clinical trial showing a survival benefit with its investigational agent tovecimig before submitting a biologics license application (BLA) for the bispecific antibody for use in patients with previously treated, advanced biliary tract cancer (BTC), according to a news release from the company.¹

Despite the recommendation, Compass plans to proceed with submitting the BLA based on findings from the phase 2/3 COMPANION-002 trial. In the study, tovecimig plus paclitaxel met its primary end point of objective response rate (ORR), reaching 18.0% compared with 5.3% for paclitaxel alone (P = .0228). The combination also produced a highly significant improvement in progression-free survival (PFS), with a median PFS of 4.7 months versus 2.6 months for paclitaxel alone, translating to a 56% reduction in the risk of progression (HR, 0.44; P < .0001).

Despite the PFS benefit, the combination did not improve overall survival (OS). Median OS was 8.9 months in the tovecimig arm versus 9.4 months in the control arm (HR, 1.05; P = .78).² Compass Therapeutics maintains, however, that that interpretation of OS was confounded by crossover.²

“While this is not the response we expected, we respect the FDA’s feedback and our priority is to work with the Agency to determine the best path forward to support our planned BLA submission and address this pressing unmet need,” Thomas Schuetz, MD, PhD, chief executive officer of Compass, stated in a news release.¹ “We remain confident that the COMPANION-002 findings, including the statistically significant improvements in PFS and ORR combined with subset analyses on survival, demonstrate clinically meaningful activity in patients with previously treated, advanced BTC.”

Crossover and Interpretation of COMPANION-002 OS Data

Earlier disclosures from COMPANION-002 provide additional context for the OS findings.² Among 168 patients randomized 2:1 to tovecimig plus paclitaxel or paclitaxel alone, 54% of patients on the control arm eventually crossed over to receive tovecimig, so that 85% of all study participants ultimately received the combination. In the intention-to-treat analysis, median OS was 8.9 months with tovecimig plus paclitaxel compared with 9.4 months in the control arm (HR, 1.05), a result the company has said is difficult to interpret given that crossover.

In a post hoc subset analysis, patients who crossed over had a median OS of 12.8 months versus 6.1 months among control-arm patients who did not cross over (HR, 0.54; P = .04). Those same crossover patients also saw a significant improvement in PFS after starting tovecimig, with a median of 3.5 months compared with 1.9 months on paclitaxel alone (HR, 0.36; P = .0016). Response by category in the tovecimig arm included complete response in 0.9% of patients, partial response in 16.2%, and stable disease in 44.1%, while 16.2% had progressive disease and 8.1% had non-complete response/non-progressive disease.²

Safety Profile

Compass reported that the safety profile observed with tovecimig plus paclitaxel in COMPANION-002 was generally consistent with data from earlier studies of tovecimig, without describing new safety findings in this update.¹ The company has not indicated that safety concerns played a role in the FDA’s recommendation for an additional survival trial.

Tovecimig Mechanism and COMPANION-002 Trial Design

Tovecimig is an investigational bispecific antibody that simultaneously targets DLL4 and VEGF-A, blocking 2 angiogenic pathways at once.¹

COMPANION-002 (NCT05506943) is a randomized phase 2/3 study evaluating tovecimig in combination with paclitaxel against paclitaxel alone in patients with previously treated, advanced BTC.² Enrolled patients had received at least 1 prior systemic regimen. Patients were stratified and randomized to receive tovecimig, also previously studied under the name CTX-009, plus paclitaxel, or paclitaxel alone, with crossover to the combination permitted for patients on the control arm following disease progression. Tovecimig has already received Fast Track and Orphan Drug designations from the FDA for this indication.

Next Steps for Tovecimig's Development

Compass plans to continue discussions with the FDA to determine the best way forward for its BLA submission. The company has not specified a timeline for completing its discussions with the FDA or for submitting its BLA.

REFERENCES

1. Compass Therapeutics provides regulatory update on tovecimig in biliary tract cancer following FDA feedback. News release. Compass Therapeutics, Inc. September 22, 2026. Accessed September 22, 2026. https://tinyurl.com/mryj6887

2. Tovecimig demonstrates statistically significant benefit in COMPANION-002 randomized phase 2/3 study in patients with biliary tract cancer. News release. Compass Therapeutics, Inc. April 27, 2026. Accessed September 22, 2026. https://tinyurl.com/2ju4emr7