Tovecimig Plus Paclitaxel Improves ORR in Advanced Biliary Tract Cancer
The primary end point of overall response rate has been met in the COMPANION-002 trial of tovecimig and paclitaxel in advanced biliary tract cancer.
Gastric/GEJ tumor: ©LASZLO - stock.adobe.com
In patients with advanced biliary tract cancer who progressed following first-line gemcitabine and platinum-based chemotherapy, the addition of the DLL4 x VEGF-A bispecific antibody tovecimig (CTX-009) to paclitaxel demonstrated a statistically significant improvement in overall response rate (ORR) compared with paclitaxel alone, according to findings from the phase 2/3 COMPANION-002 trial (NCT05506943).1
An ORR of 17.1% was seen in the tovecimig plus paclitaxel arm (n = 111) vs 5.3% in the paclitaxel-alone arm (n = 57), representing a relative improvement of 11.8% (P =.031) and meeting the primary end point of the study.
"We are thrilled to share these positive primary end point data from the COMPANION-002 study of tovecimig in patients with advanced biliary tract cancer," said Thomas Schuetz, MD, PhD, chief executive officer of Compass Therapeutics and vice chairman of the Board of Directors, in a press release. “We would like to thank all of the patients and their caregivers who have participated and continue to participate in this study. We believe these findings highlight the potential of tovecimig to provide a much-needed treatment option for the majority of patients with biliary tract cancer who have limited alternatives after first-line therapy. We look forward to discussing these data with regulatory authorities."
Tovecimig is an investigational bispecific antibody designed to simultaneously block DLL4 and VEGF-A signaling pathways.1 Preclinical and early clinical data indicate tovecimig demonstrates antitumor activity in multiple solid tumors, including responses in VEGF-resistant, heavily pretreated patients.
The COMPANION-002 trial was an open-label, multicenter, randomized study designed to evaluate the efficacy and safety of tovecimig in patients aged 18 years and older with unresectable advanced, metastatic, or recurrent biliary tract cancers, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma.2
Eligible patients had progressed after a first-line gemcitabine and platinum-based regimen, with specific inclusion criteria including measurable disease per RECIST 1.1, an ECOG performance status of 0 or 1, and adequate organ function.
Patients were randomly assigned in a 2:1 fashion to receive tovecimig at a dose of 10 mg/kg on days 1 and 15 plus paclitaxel at a dose of 80 mg/m2 on days 1, 8, and 15, or paclitaxel alone, administered in 28-day cycles. Crossover to the experimental arm was permitted upon disease progression for patients in the control arm.
The primary end point of the study was ORR per independent central radiology review assessment, and secondary endpoints were duration of response, progression-free survival, and overall survival.
In the tovecimig arm, 0.9% of patients achieved a complete response (CR), and 16.2% had partial responses (PR), with stable disease (SD) seen in 44.1%. In the control arm, no CRs were reported, and PRs were seen in 5.3% of patients.1
Safety data for tovecimig were consistent with its known toxicity profile, and an independent data monitoring committee recommended continuing the study without modifications after multiple reviews.
Further efficacy data for the study’s secondary end points are expected in the fourth quarter of 2025, as these data were immature at the time of the topline analysis. Additionally, full safety results will be reported later in 2025.
“As a treating clinician for over 20 years, I have seen firsthand how challenging a disease biliary tract cancer is,” said Juan Valle, MD, chief medical officer of the Cholangiocarcinoma Foundation, in the press release.1 “Each investigative trial helps in this fight to advance new treatment options, and I look forward to following tovecimig’s continued progress.”
References
Tovecimig (CTX-009) meets primary endpoint in the ongoing randomized phase 2/3 study in patients with biliary tract cancer. News release. Compass Therapeutics. April 1, 2025. Accessed April 1, 2025. https://tinyurl.com/yck9b733
A study of CTX-009 in combination with paclitaxel in adult patients with unresectable advanced, metastatic or recurrent biliary tract cancers (COMPANION-002). ClinicalTrials.gov. Updated August 14, 2024. Accessed April 1, 2025. https://clinicaltrials.gov/study/NCT05506943
