Multicenter randomized phase 2-3 trial of addition of tovecimig to paclitaxel as second-line therapy for advanced biliary tract cancer

Patients with previously treated biliary tract cancer (BTC) have short median overall survival (OS) and few treatment options. The multicenter randomized phase 2-3 COMPANION-002 trial evaluated addition of tovecimig (bispecific antibody targeting DLL-4 and VEGF-A) to paclitaxel for patients who received one previous line of systemic therapy for advanced BTC. Crossover from paclitaxel to tovecimig plus paclitaxel was permitted following progression. Primary endpoint was objective response rate (ORR) as assessed by blinded independent central review. A total of 168 patients were randomized 2:1 to tovecimig plus paclitaxel (n=111) or paclitaxel alone (n=57). The ORR was 18.0% with tovecimig plus paclitaxel versus 5.3% with paclitaxel (p=0.0228) and the median progression-free survival (PFS) was 4.7 versus 2.6 months (HR 0.44; p<0.0001). Among 31 patients (54%) who crossed over, post-progression PFS exceeded initial PFS (median 3.5 versus 1.9 months; HR 0.40; p=0.0035). The most common treatment-emergent adverse events with the combination were hypertension and fatigue. Grade ≥ 3 TEAEs occurred in 93.5% of patients with tovecimig plus paclitaxel and 66.7% of patients with paclitaxel alone. The authors conclude that addition of tovecimig to second-line paclitaxel significantly improved ORR and PFS among advanced BTC patients.