Randomized Phase 3 Trial of Telisotuzumab adizutecan plus bevacizumab versus trifluridine/tipiracil plus bevacizumab in refractory metastatic colorectal cancer

The primary objective is to demonstrate the superiority of telisotuzumab adizutecan plus bevacizumab over trifluridine and tipiracil plus bevacizumab in patients with refractory metastatic colorectal cancer with respect to Objective Response and Overall Survival, endpoints that directly reflect tumor shrinkage and length of life.

Secondary objectives include:

• Evaluation of Progression-Free Survival for the experimental regimen.
• Assessment of patient-reported outcomes focusing on physical functioning and overall quality of life.
• Characterization of the safety profile of telisotuzumab adizutecan plus bevacizumab.
• Determination of clinical outcomes such as duration of response and disease control.

The trial enrolled a total of 455 participants diagnosed with colorectal cancer. Both male and female adults were included, covering the age categories defined by the protocol as codes 3 and 4, which correspond to adult age groups. Eligible individuals were required to provide voluntary, signed informed consent, demonstrate capacity to consent, and have an investigator‑assessed life expectancy of at least 12 weeks. The study population comprised patients meeting these criteria, with no specific restrictions on diet, physical activity, or other lifestyle factors reported. Vulnerable subjects were not excluded, reflecting the inclusive nature of the enrollment strategy.

AndroMETa-CRC-560 is a Phase III, open-label, randomized, controlled trial comparing intravenous telisotuzumab adizutecan plus bevacizumab with oral trifluridine/tipiracil plus bevacizumab in adults with refractory metastatic colorectal cancer. Participants are screened during a baseline visit, after which eligible individuals are assigned in a 1:1 ratio to one of the two treatment arms. Study visits occur at week 0 (screening), week 1 (first infusion), then every 8 weeks for efficacy assessments, safety monitoring, and drug administration; a final end‑of‑study visit is scheduled at disease progression, withdrawal, or study completion. The primary endpoints are Objective Response assessed by blinded independent central review and overall survival; secondary endpoints include progression‑free survival, duration of response, disease control, and quality‑of‑life measures. Participant involvement extends from the screening visit through the end‑of‑study visit, with an estimated total duration of up to 24 months per subject. Early termination may occur if a participant experiences unacceptable toxicity, withdraws consent, is lost to follow‑up, or if the investigator determines that continuation is not in the participant’s best interest. The overall study recruitment period is planned from 7 May 2026 to 16 May 2029.

The experimental arm utilizes telisotuzumab adizutecan, supplied as a solution for infusion for intravenous administration. The protocol specifies a dose of 0 mg per infusion; the infusion is performed according to the study schedule and may be repeated at defined intervals. This agent is co‑administered with intravenous bevacizumab at a dose of 7.5 mg/kg.

The comparator arm comprises oral trifluridine and tipiracil in the pharmaceutical form identified as PHF00082MIG, administered at 70 mg/m². In addition, participants receive intravenous bevacizumab at 7.5 mg/kg. Both agents are given according to the designated dosing schedule for each treatment cycle.

All study medications are delivered in accordance with the trial’s dosing timetable. Intravenous infusions are prepared under aseptic conditions, with infusion rates and monitoring parameters defined in the protocol. Oral capsules are taken as instructed, and adherence is assessed by pill count and patient diary review at each study visit. Compliance with the dosing schedule is documented in the case report form, and any deviations are recorded and reported per regulatory requirements.

The primary efficacy assessments comprise Objective Response determined by Blinded Independent Central Review (BICR) of imaging studies and Overall Survival measured from the date of randomization until death from any cause. Imaging data will be submitted to the BICR for independent evaluation according to RECIST criteria, and survival status will be captured throughout the study period.

Key secondary efficacy parameters include Progression‑Free Survival, Duration of Response, and Disease Control, each assessed by BICR using the same imaging schedule applied for the primary response evaluation. Health‑related quality of life will be evaluated with the EORTC QLQ‑C30 questionnaire; changes from baseline in the physical functioning domain will be recorded at Week 13, and changes in the remaining domains will be assessed at the same time point. All patient‑reported outcomes will be collected using the validated EORTC instrument and analyzed according to prespecified statistical methods.