Tovecimig (CTX-009) in combination with paclitaxel demonstrated a statistically significant improvement in progression-free survival (PFS) compared with chemotherapy alone in patients with previously treated advanced biliary tract cancers (BTCs), meeting a key secondary end point of the phase 2/3 COMPANION-002 trial (NCT05506943).¹
The median PFS by blinded independent central review (BICR) was 4.7 months with tovecimig vs 2.6 months with paclitaxel (HR, 0.44; P < .0001). Despite this PFS benefit, the study did not meet its other secondary end point of overall survival (OS), largely due to a high rate of crossover from the control arm (54%; n = 31/57).
Overall, 85% (n = 142/168) of patients received tovecimig plus paclitaxel, yielding a pooled median OS of 8.9 months. In the intention-to-treat analysis, median OS was 8.9 months with the combination vs 9.4 months in the control arm (HR, 1.05; P = .78); similar findings were observed in the rank-preserving structural failure time analysis (HR, 1.13; P = .65), although interpretability was limited.
Among patients from the control arm who crossed over to receive tovecimig plus paclitaxel (n = 31), the median PFS improved from 1.9 months on paclitaxel (PFS1) to 3.5 months after crossover (PFS2; HR, 0.36; P = .0016). In post hoc analyses of the control arm (n = 57), patients who crossed over achieved a median OS of 12.8 months vs 6.1 months for patients who did not cross over (HR, 0.54; P = .04), despite achieving a shorter initial PFS with paclitaxel (1.9 in crossover subset vs 3.6 months in non-crossover subset; HR, 2.31; P = .007).
No new safety signals were reported in the current analysis. The most common treatment-emergent adverse effects (TEAEs) in the tovecimig arm were hypertension (69%) and fatigue (67%). The most common related grade 3 or higher TEAEs were hypertension (44%) and neutropenia (36%).
“In this study, tovecimig showed an impressive overall response rate [ORR] which translated into a clinically meaningful and highly statistically significant improvement in PFS for patients with previously treated BTC. The remarkable 56% reduction in the risk of disease progression is unprecedented in this patient population without an actionable mutation in their tumor,” Thomas Schuetz, MD, PhD, chief executive officer of Compass, stated in a news release. “It is also notable that the 31 crossover patients survived a median of 12.8 months, similar to the median OS seen in frontline studies in this setting. Including crossover, 85% of patients in the study received tovecimig in combination with paclitaxel, and the pooled median OS for all patients in the study was 8.9 months, which is also substantially longer than chemotherapy benchmarks of approximately 6 months.”
COMPANION-002 Highlights PFS Gain With Tovecimig in Biliary Tract Cancer
- Tovecimig plus paclitaxel significantly improved PFS vs paclitaxel alone (HR, 0.44; P < .0001) in patients with previously treated biliary tract cancers in COMPANION-002.
- OS was not significantly improved in the intention-to-treat population; likely confounded by a high crossover rate (54%), with post-hoc analyses suggesting longer survival among crossover recipients.
- The combination previously met the study’s primary ORR end point and demonstrated a manageable safety profile with no new safety signals.
What prior data have been reported from COMPANION-002?
Topline findings reported in April 2025 showed that the study met its primary end point of improved ORR with the tovecimig plus paclitaxel regimen (n = 111) vs paclitaxel alone (n = 57), with ORRs of 17.1% and 5.3%, respectively. This translated to a statistically significant relative improvement of 11.8% (P = .031).2
In the tovecimig arm, the complete response (CR) rate was 0.9%, the partial response (PR) rate was 16.2%, and the stable disease (SD) rate was 44.1%. Progressive disease (PD) and non-CR/non-PD occurred in 16.2% and 8.1% of patients, respectively. In the control arm, no patients had a CR; respective PR, SD, PD, and non-CR/non-PD rates were 5.3%, 33.3%, 42.1%, and 3.5%. Additionally, 14.4% and 15.8% of patients in the tovecimig and paclitaxel arms, respectively, were not evaluable. Tovecimig’s safety profile in COMPANION-002 was consistent with the agent’s known toxicities.
Of note, tovecimig previously received FDA fast track designation and orphan drug designation for the treatment of patients with metastatic or locally advanced biliary tract cancers, reflecting the unmet need in this setting.3,4
“These findings reinforce our belief that tovecimig can address a significant unmet need for patients with limited and insufficient treatment options,” Schuetz added.1 “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.”
What is the design of COMPANION-002?
This ongoing open-label, multicenter, randomized phase 2/3 study enrolled patients who were at least 18 years of age and had histologically confirmed biliary tract cancer, including intrahepatic or extrahepatic cholangiocarcinoma and gallbladder cancer.1,5 Patients were required to have experienced radiologically documented disease progression on least 1 prior line of systemic therapy. Additional inclusion criteria included measurable disease per RECIST 1.1 criteria and an ECOG performance status of 0 or 1. Notably, patients who received prior perioperative therapy were allowed to enroll at discretion of the trial sponsor’s medical monitor, as were those who had their first-line treatment regimen modified due to toxicity prior to disease progression.
Upon enrollment, patients were randomly assigned 2:1 to receive tovecimig at 10 mg/kg on days 1 and 15 plus paclitaxel at 80 mg/m² on days 1, 8, and 15 of every 28-day cycle; or the same dosing schedule of paclitaxel alone.1 The study’s primary end point was ORR; secondary end points included PFS, OS, and duration of response.
References
- Tovecimig demonstrates statistically significant benefit in COMPANION-002 randomized phase 2/3 study in patients with biliary tract cancer. News Release. Compass Therapeutics. April 27, 2026. Accessed April 27, 2026. https://investors.compasstherapeutics.com/news-releases/news-release-details/tovecimig-demonstrates-statistically-significant-benefit
- 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 27, 2026. https://investors.compasstherapeutics.com/news-releases/news-release-details/tovecimig-ctx-009-meets-primary-endpoint-ongoing-randomized
- Compass Therapeutics receives FDA fast track designation for the investigation of CTX-009 in combination with paclitaxel for the treatment of patients with metastatic or locally advanced biliary tract tumors that have been previously treated. News release. Compass Therapeutics. April 25, 2024. Accessed April 27, 2026. https://investors.compasstherapeutics.com/news-releases/news-release-details/compass-therapeutics-receives-fda-fast-track-designation
- 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 27, 2026. https://www.koreabiomed.com/news/articleView.html?idxno=31224
- 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 April 20, 2025. Accessed April 27, 2026. https://clinicaltrials.gov/study/NCT05506943
