Compass Therapeutics publishes COMPANION-002 BTC trial data in JCO

Compass Therapeutics has published peer-reviewed results from its COMPANION-002 trial in the Journal of Clinical Oncology (JCO), with an oral presentation delivered at the ESMO Congress in Madrid on 24 October. The data show that tovecimig, a bispecific antibody, combined with paclitaxel produced a statistically significant improvement in response rates and progression-free survival against a chemotherapy-alone control in patients with previously treated, advanced biliary tract cancer (BTC).

The randomised Phase 2/3 study enrolled 168 patients who had received one prior systemic therapy and were without an actionable mutation carrying an approved targeted treatment. The combination arm achieved an objective response rate (ORR) of 18.0% compared with 5.3% for paclitaxel alone, as assessed by blinded independent central review (p=0.0228). Median progression-free survival (PFS) reached 4.7 months versus 2.6 months, representing a hazard ratio of 0.44 (p<0.0001), the 56% risk reduction highlighted in the release.

Trial results in detail

The disease control rate, which captures patients whose cancer responded or remained stable, was 62.2% in the combination arm versus 36.8% in the control arm (p=0.0018). Median duration of response was 4.9 months. In a prespecified subgroup of patients with intrahepatic cholangiocarcinoma, who accounted for 92 of the 168 participants, ORR was 15.3% versus 0% and median PFS was 5.1 versus 3.0 months (HR=0.32), results broadly consistent with the overall population.

Overall survival (OS) findings are more nuanced. Because 54% of patients in the control arm crossed over to receive tovecimig after confirmed disease progression, the intent-to-treat OS analysis was confounded and showed no statistically significant difference. A post hoc crossover-adjusted analysis using the Two-Stage Estimation method produced an OS hazard ratio of 0.85 (95% CI, 0.59-1.26; p=0.53). The company acknowledges this remains exploratory; an unadjusted OS benefit has not been demonstrated.

Safety signals were broadly in line with the known anti-VEGF class profile. The most common treatment-emergent adverse events in the combination arm were hypertension (69%) and fatigue (67%). Grade 3 or higher events occurred in 93.5% of patients receiving the combination and 64.2% of those on paclitaxel alone. Treatment discontinuations due to adverse events were reported in 27.8% and 11.3% of patients respectively, and events leading to death in 5.6% versus 1.9%. No hypertensive crises or unexpected cardiovascular toxicities were recorded.

Nilofer Azad of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, who presented the data at ESMO, described the improvements in response rate and PFS as "encouraging for patients in this setting" and noted activity in patients who switched to tovecimig after progression on paclitaxel alone.

Market context and regulatory path

BTC is estimated to affect roughly 26,500 patients annually in the United States, and there is currently no FDA-approved second-line treatment for patients without an actionable mutation. That gap has attracted growing attention from developers of anti-angiogenic and immune-oncology combinations, with approved first-line agents such as durvalumab plus chemotherapy now defining a shifting baseline for second-line expectations.

Tovecimig is a DLL4 x VEGF-A bispecific antibody designed to block two angiogenic pathways simultaneously. The FDA has granted both Fast Track and Orphan Drug Designation to the candidate. Compass said it will continue working with the FDA toward a regulatory pathway, though neither a filing timeline nor a potential approval date was disclosed. Additional analyses from COMPANION-002, including patient-reported quality of life data and translational research, are described as ongoing. Investors and clinicians will want to see whether those datasets, along with any confirmatory OS evidence, can support a robust regulatory package for a disease where second-line options remain severely limited.