Tovecimig Improves PFS, But Misses OS End Point in Biliary Tract Cancer

Tovecimig (CTX-009) in combination with paclitaxel significantly improved progression-free survival (PFS), but not overall survival (OS), compared with paclitaxel alone in patients with previously treated biliary tract cancer (BTC), according to findings from the phase 2/3 COMPANION-002 trial (NCT05506943).¹

By blinded independent central review, the median PFS was 4.7 months with tovecimig plus paclitaxel versus 2.6 months with paclitaxel alone (HR, 0.44; P < .0001), representing a 56% reduction in the risk of disease progression or death.¹ 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).¹

Compass Therapeutics, the developer of tovecimig, noted that interpretation of OS was confounded by crossover, with 31 (54%) of 57 patients assigned to the control arm receiving tovecimig after progression.¹ In addition, approximately 85% of all patients enrolled in the study ultimately received tovecimig at some point during their treatment course, further limiting the ability to distinguish survival differences between randomized groups.¹

Among crossover patients, outcomes suggested a potential treatment-associated benefit. Median OS in patients who crossed over to tovecimig was 12.8 months compared with 6.1 months in those who did not receive subsequent tovecimig (HR, 0.54; P = .04).¹ These findings support a potential survival impact with exposure to the agent, though randomized OS comparisons were not interpretable due to treatment contamination.

Tovecimig also demonstrated activity across other efficacy measures. The study previously met its primary end point of objective response rate (ORR), with responses observed in 17.1% of patients receiving the combination compared with 5.3% in those treated with paclitaxel alone (P = .031).²

In exploratory analyses, disease control was further supported by a progression-free survival after crossover (PFS2) signal. Among patients who crossed over, median PFS2 was 3.5 months compared with 1.9 months in those who did not receive tovecimig after progression (HR, 0.36; P = .0016).¹

The safety profile of tovecimig in combination with paclitaxel was reported as manageable, with no new safety signals identified.¹ Adverse events were consistent with expected effects of angiogenesis pathway inhibition, including VEGF- and DLL4-related toxicities, and aligned with prior experience in earlier-phase studies of the agent.

“These findings reinforce our belief that tovecimig can address a significant unmet need for patients with limited and insufficient treatment options. We are immensely grateful to the patients, investigators, and clinical teams who made this study possible, and we look forward to presenting the full dataset at an upcoming medical meeting. We are now focused on engaging with the FDA to bring this much needed therapy to the cholangiocarcinoma community as quickly as possible,” Thomas Schuetz, MD, PhD, chief executive officer of Compass, stated in a press release.

Study Design and Patient Population

COMPANION-002 is a randomized, multicenter phase 2/3 trial evaluating tovecimig plus paclitaxel versus paclitaxel alone in patients with advanced BTC following prior gemcitabine-based therapy.¹ A total of 168 patients were randomized in a 2:1 ratio to receive tovecimig plus paclitaxel (n = 111) or paclitaxel alone (n = 57).² 

The primary end point of the trial was ORR as confirmed by independent central radiology review and key secondary end points include PFS and OS. Patients in the control arm who progressed could cross over to receive tovecimig plus paclitaxel after centrally confirmed progression.

All patients were dosed with 80 mg/m2 of paclitaxel on days 1, 8 and 15 of every 28-day cycle. Patients in the tovecimig arm were also dosed with 10 mg/kg of tovecimig on days 1 and 15 of each 28-day cycle. The primary endpoint of the trial is ORR as confirmed by independent central radiology review and secondary endpoints include PFS, OS and DoR, among others. Patients in the paclitaxel-only arm who progressed could cross over to the tovecimig plus paclitaxel arm after centrally confirmed progression if they also still met the enrollment criteria for the study.

“Patients with advanced biliary tract cancer have an urgent need for better treatment options,” Juan Valle, MD, chief medical officer of the Cholangiocarcinoma Foundation, stated in the news release. “These results are a significant step forward and I anticipate that, if approved, it will meaningfully change the way physicians care for these patients. I also applaud Compass for putting patients first in the design of this study by allowing patients to crossover to receive treatment with tovecimig. These patients clearly benefited from this innovative therapy. I look forward to supporting Compass as they work to bring tovecimig to patients with cholangiocarcinoma.”

REFERENCES

1. Compass Therapeutics. Tovecimig demonstrates statistically significant benefit in COMPANION-002 study in biliary tract cancer. Published April 27, 2026. Accessed April 28, 2026. https://tinyurl.com/4py9bnu2

2. Compass Therapeutics. Tovecimig meets primary endpoint in phase 2/3 BTC study. Published April 1, 2025. Accessed April 28, 2026.