Tovecimig Plus Paclitaxel Improves ORR vs Paclitaxel Alone in Biliary Tract Cancer

Tovecimig (CTX-009) plus paclitaxel improved objective response compared with paclitaxel alone in patients with previously treated advanced biliary tract cancer, according to data from the phase 2/3 COMPANION-002 trial (NCT05506943) presented at the 2026 ESMO Congress.¹

Among patients randomly assigned to receive tovecimig plus paclitaxel (n = 111) or paclitaxel alone (n = 57), the objective response rates (ORRs) by blinded independent central review (BICR) were 18.0% vs 5.3%, respectively (P = .0228), meeting the trial’s primary end point. The best overall response was complete in 0.9% and partial in 17.1% of patients receiving the combination, vs respective rates of 0% and 5.3% with paclitaxel alone, and the median duration of response (DOR) with the combination was 4.9 months. The disease control rates (DCRs) were 62.2% vs 36.8%, respectively (P = .0018). The median progression-free survival (PFS) values per BICR were 4.7 months (95% CI, 3.9-5.6) vs 2.6 months (95% CI, 1.9-3.6), respectively (HR, 0.44; 95% CI, 0.30-0.66; P < .0001).

The median overall survival (OS) was 8.9 months (95% CI, 7.0-11.2) with the combination vs 9.4 months (95% CI, 6.5-13.5) with paclitaxel alone (HR, 1.05; 95% CI, 0.7-1.5; P = .779). Notably, the OS analysis was confounded by crossover, as 31 patients (54%) in the paclitaxel arm went on to receive tovecimig.

“Altogether, this combination represents a promising new strategy for patients with biliary tract cancer,” Nilofer S. Azad, MD, of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland, stated in a presentation of the data.

How was the phase 2/3 COMPANION-002 trial designed?

Tovecimig is a bispecific antibody directed against VEGF-A and DLL4. Inhibiting VEGF-A curbs VEGF receptor 2–driven migration and proliferation of endothelial cells, whereas inhibiting DLL4 interferes with tip-stalk cell organization and promotes unproductive branching; together, these effects impair tumor vessel growth and organization.

COMPANION-002 is a multicenter, open-label trial.^1,2 Eligible adult patients had advanced, metastatic, or unresectable biliary tract cancer that had progressed after 1 gemcitabine- and platinum-containing regimen for advanced disease, at least 1 measurable lesion per RECIST 1.1 criteria, and an ECOG performance status of 0 or 1. Patients with known actionable alterations were excluded when a targeted second-line option existed. Patients were randomly assigned 2:1 to receive 28-day cycles of tovecimig at 10 mg/kg on days 1 and 8 plus paclitaxel at 80 mg/m² on days 1, 8, and 15, or paclitaxel alone on the same schedule. Randomization was stratified by tumor location (intrahepatic vs other), ECOG performance status (0 vs 1), and disease status (locally advanced vs metastatic). Patients in the paclitaxel arm could cross over to receive tovecimig plus paclitaxel upon BICR-confirmed progressive disease. The primary end point was ORR by BICR, and secondary end points included PFS per BICR, DCR, OS, DOR, a second PFS analysis, safety, and quality of life.

Patients had a median age of 65.0 years in the combination arm vs 63.0 years in the paclitaxel-alone arm.¹ Intrahepatic primary tumors were reported in 55.9% of patients in the combination arm and 52.6% of those in the paclitaxel arm, and 89.2% vs 91.2% of patients, respectively, had metastatic disease at study entry.

What did earlier COMPANION-002 results show with tovecimig plus paclitaxel in biliary tract cancer?

In an earlier analysis reported in April 2025, the ORR with tovecimig plus paclitaxel was 17.1% (n = 111), and the difference vs paclitaxel alone (ORR, 5.3%) was statistically significant (P = .031).³

Did crossover to tovecimig plus paclitaxel change outcomes in patients with biliary tract cancer in COMPANION-002?

In a post hoc analysis of patients who crossed over from the paclitaxel-alone arm (n = 31), the ORR with tovecimig plus paclitaxel was 6.5%, and the DCR was 48.4%, with stable disease the most common response, reported in 41.9% of patients.¹ The median PFS was 1.9 months (95% CI, 1.7-3.0) before crossover and 3.5 months (95% CI, 1.7-9.7) after crossover (HR, 0.40; 95% CI, 0.2-0.7; P = .0035). The median OS was 12.8 months (95% CI, 7.6-15.6) among patients who crossed over vs 6.1 months (95% CI, 4.2-9.8) among those who did not (n = 26; HR, 0.54; 95% CI, 0.3-0.98; P = .04).

What was the safety profile of tovecimig plus paclitaxel in advanced biliary tract cancer?

The safety population included 108 patients in the combination arm and 53 patients in the paclitaxel arm. The median treatment exposure duration was 14.4 weeks with the combination vs 10.9 weeks with paclitaxel alone. In the combination arm, tovecimig discontinuation occurred in 30.6% of patients, and paclitaxel discontinuation was reported in 28.7% of patients; in the paclitaxel-alone arm, this rate was 15.1%.

The most common treatment-related AEs were fatigue and neutropenia, and grade 3 or higher hypertension was also common with the combination. Across patients in the combination and control arms, respectively, grade 3 or higher sepsis occurred in 5% vs 4%, septic shock was reported in 2% vs 0%, biliary tract infection was seen in 1% vs 0%, and embolism occurred in 3% vs 2%. Two deaths in the combination arm were considered treatment related (sepsis with renal failure, and septic shock). The investigators described the safety profile of the combination as controllable and in line with findings from earlier studies of antiangiogenic agents plus chemotherapy.

Disclosures: Azad reported receiving honoraria from Agenus, Astellas, AstraZeneca, Bristol Myers Squibb, Beigene, Eli Lilly, GlaxoSmithKline, Incyte, Revolution Medicines, and Servier; being a stockholder in former Haystack, former Cage Pharma, and former Tempus; and receiving research funding from AstraZeneca, Atlas, Bayer, Beigene, Bristol Myers Squibb, Compass, Incyte, Pfizer/Seagen, Revolution Medicines, Syndax, and Taiho.

References

1. Azad NS, Hu I, Pathak P, et al. A randomized trial of paclitaxel ± tovecimig in previously treated patients with advanced biliary tract cancer. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract 459O.
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 September 2, 2026. Accessed October 24, 2026. https://clinicaltrials.gov/study/NCT05506943
3. 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 1, 2025. https://investors.compasstherapeutics.com/news-releases/news-release-details/tovecimig-ctx-009-meets-primary-endpoint-ongoing-randomized