Tovecimig Plus Paclitaxel Meets ORR End Point in Second-Line Biliary Tract Cancer

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The addition of the DLL4 x VEGF-A bispecific antibody tovecimig (CTX-009) to paclitaxel led to an improvement in overall response rate (ORR) compared with paclitaxel alone in patients with advanced biliary tract cancer who had received 1 prior line of therapy, meeting the primary end point of the phase 2/3 COMPANION-002 trial (NCT05506943).1

Topline findings announced by Compass Therapeutics demonstrated that patients treated with tovecimig plus paclitaxel (n = 111) experienced an ORR of 17.1% compared with 5.3% for those given paclitaxel alone (n = 57), translating to a statistically significant relative improvement of 11.8% (P = .031). In the tovecimig arm, 1 patient (0.9%) achieved a complete response (CR), and 16.2% had partial responses (PR). The rates of stable disease (SD), progressive disease (PD), and non-CR/non-PD were 44.1%, 16.2%, and 8.1%, respectively; 14.4% of patients were not evaluable (NE). In the control arm, no patients reached a CR; the PR, SD, PD, and non-CR/non-PD rates were 5.3%, 33.3%, 42.1%, and 3.5%, respectively. Additionally, 15.8% of patients were NE.

"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," Thomas Schuetz, MD, PhD, chief executive officer of Compass Therapeutics and vice chairman of the Board of Directors, stated in a news 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."

The open-label, multicenter, randomized COMPANION-002 trial enrolled patients at least 18 years of age with histologically or cytologically confirmed unresectable advanced, metastatic, or recurrent biliary tract cancers, including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary carcinoma.2 Radiologically documented progression following a first-line regimen containing gemcitabine and platinum-based chemotherapy was required. Notably, patients who received prior perioperative therapy were allowed to enroll at discretion of the trial sponsor’s medical monitor, as were those who had their first-line treatment regimen modified due to toxicity prior to disease progression.

Other key inclusion criteria consisted of at least 1 measurable lesion per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks, and adequate bone marrow, hepatic, and renal function. Patients eligible to receive targeted therapy after first-line chemotherapy were excluded from enrollment.

Patients were randomly assigned 2:1 to receive tovecimig at 10 mg/kg on days 1 and 15 plus paclitaxel at 80 mg/m2 on days 1, 8, and 15 of every 28-day cycle; or the same paclitaxel regimen alone.1 Notably, crossover to the experimental arm was allowed for patients in the control arm upon centrally confirmed disease progression, permitting they still met the study’s enrollment criteria.

ORR per independent central radiology review assessment served as the trial’s primary end point. Secondary end points comprised duration of response, progression-free survival, and overall survival.

Additional efficacy data for key secondary end points are expected to be reported in the fourth quarter of 2025. Data for these end points were immature at the time of the topline analysis.

Regarding safety, results for tovecimig were consistent with the known toxicity profile of the agent. During 4 reviews of safety data during the study, an independent data monitoring committee recommended the continuation of the study without modification after each meeting. Full safety findings will be reported with the additional data later in 2025.

References

1. 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://investors.compasstherapeutics.com/news-releases/news-release-details/tovecimig-ctx-009-meets-primary-endpoint-ongoing-randomized
2. 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