The U.S. Food and Drug Administration has instructed Compass Therapeutics Inc. to conduct a new survival trial for its investigational drug tovecimig—a DLL4 x VEGF-A bispecific antibody—in patients with previously treated, advanced biliary tract cancer. The agency requires evidence of a survival benefit before the company can submit a Biologics License Application (BLA) for regulatory approval.
Compass, which holds Fast Track and Orphan Drug Designations for tovecimig, has not yet agreed to the additional trial. The company argues that the COMPANION-002 Phase 2/3 study already provides robust data, including a statistically significant improvement in progression-free survival (PFS). In that trial, tovecimig combined with paclitaxel yielded a median PFS of 4.7 months—nearly double the 2.6 months seen with paclitaxel alone—and a 56% reduction in disease progression risk (hazard ratio of 0.44, p<0.0001). The objective response rate also improved from 5.3% with paclitaxel alone to 18.0% with the combination (p=0.0228).
However, overall survival (OS) did not meet statistical significance in the trial, a limitation the FDA has cited as a key concern. Compass attributes this to high crossover rates—where patients in the control arm later received tovecimig—and prolonged survival in some crossover patients, which skewed the analysis. The company maintains that the PFS data, along with its engagement with the FDA, should suffice for BLA submission.
Biliary tract cancer remains a challenging disease with poor survival outcomes, particularly for patients who have received prior treatments. The FDA’s insistence on a survival benefit reflects broader regulatory scrutiny of oncology drug approvals, where efficacy is increasingly measured by overall survival as a primary endpoint. Compass Therapeutics, led by CEO Thomas Schuetz, is now evaluating the FDA’s request while preparing for a potential BLA submission.
Tovecimig’s development has been supported by FDA designations, underscoring its potential to address a critical unmet need in biliary tract cancer treatment.
