COMPANION-002: A Randomized Phase 2/3 Trial of Tovecimig Plus Paclitaxel versus Paclitaxel Alone as a Second-line Therapy in Patients with Advanced Biliary Tract Cancer

Purpose Patients with previously treated biliary tract cancer (BTC) have a short median overall survival (OS), and few treatment options. Tovecimig, a bispecific antibody to delta-like ligand-4 and vascular endothelial growth factor (VEGF)-A, was evaluated in combination with paclitaxel in COMPANION-002, a randomized phase 2/3 study in pretreated patients with advanced BTC. Methods Patients with advanced BTC with one prior systemic therapy were randomized to paclitaxel (80 mg/m 2 ; days 1, 8 and 15) with or without tovecimig (10 mg/kg; days 1 and 15). The primary endpoint was RECIST v1.1-defined objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary endpoints included progression-free survival (PFS) and OS. Crossover from the paclitaxel control arm to tovecimig plus paclitaxel was permitted following BICR-confirmed progression. Results 168 patients were randomized 2:1 to tovecimig+paclitaxel (n=111) or paclitaxel alone (n=57). Tovecimig+paclitaxel significantly improved BICR-assessed ORR (18.0% vs 5.3%; P =.0228) and PFS (4.7 vs 2.6 months; hazard ratio [HR], 0.44; P <.0001). Among 31 patients (54%) who crossed over, post-progression PFS (time from crossover to subsequent second progression) exceeded initial PFS (PFS from randomization to initial progression on paclitaxel; 3.5 vs 1.9 months; HR, 0.40; P =.0035). Overall, 142 patients (85%) received tovecimig; no difference in OS was observed (HR, 1.05; P =.779). The most common treatment-emergent adverse events (TEAEs) with tovecimig+paclitaxel were hypertension (69.4%) and fatigue (66.7%). Grade ≥3 TEAEs occurred in 93.5% and 64.2% of patients treated with tovecimig+paclitaxel and paclitaxel alone, respectively. Conclusion Tovecimig combined with paclitaxel significantly improved ORR and PFS versus paclitaxel alone as second-line therapy for patients with BTC.