Announcement • Apr 29
Compass Therapeutics Announces Statistically Significant Benefit of Tovecimig in Companion-002 Study
Compass Therapeutics, Inc. announced that it met the key secondary endpoint of PFS and showed additional compelling results in the randomized COMPANION-002 study, which evaluated tovecimig plus paclitaxel versus paclitaxel alone in patients with unresectable advanced, metastatic or recurrent biliary tract cancer (BTC) treated in the second-line setting. Tovecimig (a DLL4 x VEGF-A bispecific antibody) in combination with paclitaxel demonstrated a highly statistically significant improvement versus paclitaxel alone in the key secondary endpoint of median progression-free survival (PFS) of 4.7 months versus 2.6 months, providing a 56% reduction in the risk of progression (hazard ratio=0.44, p). Secondary endpoint analyses of overall survival (OS) were confounded by both high crossover (54%) and notably prolonged survival in crossover patients randomized to the control arm then treated with tovecimig and, therefore, did not meet statistical significance. In a subset analysis of the patients in the control arm, the median OS of the crossover patients was 12.8 months vs. 6.1 months in patients who did not crossover (hazard ratio=0.54, p=0.04). 85% of patients in the study received tovecimig with a pooled median OS of 8.9 months. Tovecimig in combination with paclitaxel met the primary endpoint of overall response rate (ORR) in the study with an ORR of 17.1% vs. 5.3% in the paclitaxel control arm (p=0.031). The complete dataset, including Duration of Response (DoR), will be presented at a medical conference later this year. Primary Endpoint (previously announced in April 2025): Overall Response Rate: 17.1% ORR for tovecimig in combination with paclitaxel (19 of 111 patients) including one complete response, compared to 5.3% for paclitaxel alone (3 of 57 patients), in patients with BTC in the second line setting. This 11.8% improvement in ORR for those receiving tovecimig was statistically significant (p=0.031). All responses were assessed by blinded independent central review (BICR). Key Secondary Endpoints: Progression-Free Survival (PFS): Tovecimig in combination with paclitaxel demonstrated a statistically significant improvement in median PFS of 4.7 months compared to 2.6 months for paclitaxel alone (HR=0.44, p). In the ITT OS analysis, tovecimig in combination with paclitaxel had a median OS of 8.9 months compared to 9.4 months for the control arm, which included 26 patients (46%) who received paclitaxel alone and 31 patients (54%) who crossed over to receive tovecimig in combination with paclitaxel (HR=1.05, p=0.78). In the rank-preserving structural failure time (RPSFT) OS analysis, the combination also had a median OS of 8.9 months compared to 9.4 months for paclitaxel alone (HR=1.13, p=0.65). Though the RPSFT analysis is intended to adjust for crossover, its validity depends on certain assumptions that were not met in this study and thus its results here are largely uninterpretable. Progression-Free Survival of Crossover Patients (PFS2): An additional, pre-specified secondary endpoint analyzed PFS in the patients in the paclitaxel arm who crossed over to receive tovecimig plus paclitaxel. In this analysis, the pre-crossover PFS (PFS1) on paclitaxel alone was compared to PFS with tovecimig post-crossover (PFS2) in the same crossover patients (n=31). In this subset, tovecimig demonstrated a statistically significant improvement with median PFS2 of 3.5 months after treatment with tovecimig compared to median PFS1 of 1.9 months for paclitaxel (HR=0.36, p=0.0016). Post Hoc Subset Analyses: OS of Paclitaxel Control Arm (Crossover vs. Non-Crossover): In an analysis of OS in all patients randomized to the paclitaxel control arm (n=57), crossover patients who subsequently received tovecimig demonstrated a statistically significant improvement in median OS of 12.8 months compared to 6.1 months for non-crossover patients who received only paclitaxel (HR=0.54, p=0.04). PFS of Paclitaxel Control Arm (Crossover vs. Non-Crossover): Another analysis of these same patients randomized to the paclitaxel control arm (n=57) demonstrated that the crossover patients initially progressed faster on paclitaxel monotherapy compared to the non-crossover patients, with a median PFS of 1.9 months versus 3.6 months (HR=2.31, p=0.007). Thus, notably, despite progressing more quickly on initial paclitaxel monotherapy, crossover patients still demonstrated a statistically significant median 12.8 months OS after being treated with tovecimig. Safety: Tovecimig was generally well tolerated and the safety profile was consistent with previously reported data from prior studies, with no new safety signals. The most commonly reported treatment emergent adverse events in the tovecimig combination arm were hypertension (69%) and fatigue (67%). The most common related treatment-emergent adverse events of Grade 3 or higher included hypertension (44%) and neutropenia (36%). COMPANION-002 is a Phase 2/3 randomized, controlled study of tovecimig in patients with unresectable advanced, metastatic or recurrent biliary tract cancers who have received one prior systemic chemotherapy regimen (clinical trial information: NCT05506943). The study enrolled 168 adult patients, randomized in a 2:1 ratio to receive tovecimig plus paclitaxel (n=111) or paclitaxel alone (n=57). All patients were dosed with 80 mg/m2 of paclitaxel on days 1, 8 and 15 of every 28-day cycle. Patients in the tovecimig arm were also dosed with 10 mg/kg of tovecimig on days 1 and 15 of each 28-day cycle. The primary endpoint of the trial is ORR as confirmed by blinded independent central radiology review and secondary endpoints include PFS, OS, and DoR, among others. Patients in the paclitaxel-only arm who progressed could cross over to the tovecimig plus paclitaxel arm after centrally confirmed progression if they also still met the enrollment criteria for the study.
