Tovecimig/Paclitaxel Meets PFS, Misses OS End Points in 2L Biliary Tract Cancer

Developers announced secondary end point results from the phase 2/3 COMPANION-002 trial (NCT05506943), which evaluated the treatment combination of tovecimig plus paclitaxel vs paclitaxel alone in the treatment of patients with unresectable advanced, metastatic, or recurrent biliary tract cancer (BTC) treated in the second-line setting.^1,2

With a data cutoff in April 2026, the key secondary end point of progression-free survival (PFS) was met, with a median PFS per blinded independent central review (BICR) of 4.7 months with tovecimig plus paclitaxel vs 2.6 months with paclitaxel alone (HR, 0.44; P <.0001).

Notably, the experimental combination did not meet the secondary end point of overall survival (OS), with a median OS in the intention-to-treat analysis of 8.9 months in the tovecimig arm vs 9.4 months in the control arm (HR, 1.05; P = .78). In both the press release and a subsequent investor call, the developer attributed this to the high rate of patients (54%) who crossed over from the control arm to the tovecimig arm.² In the rank-preserving structural failure time (RPSFT) OS analysis, the median OS remained 8.9 months vs 9.4 months, respectively (HR, 1.13; P = .65). The developer noted that while the RPFST OS is meant to adjust for cross over, “it’s validity depends on certain assumptions that were not met in this study”.¹

Additionally, a pre-specified secondary end point analyzed PFS in the patients enrolled in the paclitaxel arm who crossed over to receive the experimental combination. For this analysis, the pre-crossover PFS was compared with the PFS in those receiving toveciming post-crossover in the same 31 patients who crossed over. The median PFS2 was statistically significant, with values of 3.5 months after treatment with tovecimig vs 1.9 months with paclitaxel (HR, 0.36; P = .0016).

Post-hoc subset analyses were also shared in the release. In an analysis of all patients randomly assigned to the paclitaxel control arm (n = 57), the median OS was 12.8 months for patients who crossed over to the tovecimig arm vs 6.1 months in those who only received paclitaxel (HR, 0.54; P = .04). Further, another analysis of these patients revealed that the patients who crossed over progressed faster on paclitaxel monotherapy compared with the patients who did not crossover, with median PFS values of 1.9 months vs 3.6 months, respectively (HR, 2.31; P = .007).

The developers noted that, despite the faster initial progression among patients who crossed over, the median OS was longer for them.

Regarding safety, no new safety signals were identified with tovecimig. The most common treatment-emergent adverse events (TEAEs) were hypertension (69%) and fatigue (67%); the most common related TEAEs of grade 3 or higher were hypertension (44%) and neutropenia (36%).

In April 2025, it was announced that tovecimig plus paclitaxel met the primary end point of overall response rate (ORR) per BICR.³ The most recently reported ORRs were 17.1% with tovecimig plus paclitaxel and 5.3% with paclitaxel alone (P = .031). One complete response (0.9%) and 18 partial responses (16.2%) were observed in the experimental arm vs 0 complete responses and 3 partial responses (5.3%) in the control arm.

The developer plans to share the complete data set, including duration of response, at a medical conference later this year.

“In this study, tovecimig showed an impressive 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,” stated Thomas Schuetz, MD, PhD, chief executive officer of Compass, in the press release.¹ “It is also notable that the 31 patients who crossed over survived a median of 12.8 months, similar to the median OS seen in front-line 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.”

The COMPANION-002 Study Design

Patients enrolled in the study were randomly assigned in a 2:1 ratio to receive either tovecimig plus paclitaxel (n = 111) or paclitaxel alone (n = 57), with treatment continuing until disease progression per RECIST v1.1 as confirmed by Independent Central Radiology. Once patients in the paclitaxel arm experienced progression, they were permitted to cross over—54% (n = 31) elected to cross over to the tovecimig regimen. Tovecimig was administered at 10 mg/kg on days 1 and 15 of each 28-day treatment cycle, and paclitaxel was given at 80 mg/m² on days 1, 8, and 15 of each cycle; paclitaxel was given at the same dose and schedule in both arms.

The primary end point of the trial was ORR, with key secondary end points of PFS, OS, and duration of response.

Among the patients enrolled in the tovecimig plus paclitaxel arm and the paclitaxel arm, the median ages were 65.0 years and 63.0 years, respectively, with 52.3% and 57.9% being female, 75.7% and 70.2% being White, 55.9% and 52.6% having primary disease allocation of intrahepatic, 52.3% and 52.6% having an ECOG performance status of 1, and 89.2% and 91.2% having metastatic disease.

“Patients with advanced [BTC] have an urgent need for better treatment options,” added Juan Valle, MD, chief medical officer of the Cholangiocarcinoma Foundation.¹ “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.”

The developer currently plans to meet with the FDA to discuss the data in advance of a biologics license application (BLA) submission. This treatment previously received orphan drug designation in April 2026.⁴

References

1. 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 29, 2026. https://tinyurl.com/hstw28hx
2. COMPANION-002: secondary endpoints. Corporate Presentation. Compass Therapeutics. April 27, 2026. Accessed April 29, 2026. https://tinyurl.com/47cxr2ud
3. 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 29, 2026. https://tinyurl.com/3nvv425s
4. 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 29, 2026. https://tinyurl.com/3d7ry9fw