Colorectal cancer (CRC) is the third most common type of cancer diagnosed worldwide. The purpose of this study is to assess the adverse events and change in disease activity of telisotuzumab adizutecan plus bevacizumab compared to standard of care (SOC) of LONSURF (trifluridine and tipiracil) plus bevacizumab in adult participants with c-Met over-expressed refractory metastatic colorectal cancer (mCRC).
Telisotuzumab adizutecan is an investigational drug being developed for the treatment of CRC. Participants will then be randomized into 2 groups called treatment arms. One group will receive telisotuzumab adizutecan with bevacizumab in different doses. Another group will receive standard of care (SOC), trifluridine and tipiracil (LONSURF), with Bevacizumab. Up to approximately 700 adult participants with refractory mCRC, will be enrolled in the study in approximately 125 sites globally.
In this Phase 3, one of two groups will receive doses of Intravenous (IV) telisotuzumab adizutecan + bevacizumab and other group will receive oral SOC of trifluridine/tipiracil (LONSURF)+ Intravenous (IV) bevacizumab. The study will run for a duration of approximately of 36 months.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
Must voluntarily sign and date an informed consent, approved by an Ethics Committee (IEC)/ Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures. Participants must have the capacity to consent in the opinion of the investigator.
Life expectancy >= 12 weeks per investigator assessment
Prior systemic regimen containing c-Met targeting agent (e.g., antibody, antibody drug conjugate, bispecific) or any other unapproved investigational agent.
History of allergic reactions or hypersensitivity to bevacizumab or any of its excipients, or to compounds similar to trifluridine/tipiracil.
History of hypersensitivity to Chinese Hamster Ovary cell products or other recombinant human or humanized antibodies.
History of clinically significant (per investigator's judgment) drug or alcohol abuse within the last 6 months.
Parallel
Telisotuzumab adizutecan
DrugIntravenous (IV)
Bevacizumab
DrugIntravenous (IV)
Trifluridine/Tipiracil
DrugOral
Phase 3: Objective Response (OR) as assessed by Blinded Independent Central Review (BICR)
Confirmed complete response (CR) or confirmed partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Phase 3: Overall Survival (OS)
OS is defined as the time from randomization to the event of death from any cause.
Phase 3: Progression-Free Survival (PFS) Assessed by Blinded Independent Central Review (BICR)
PFS is defined as the time from randomization to the first occurrence of radiographic progression based on RECIST v1.1 or death from any cause, whichever occurs earlier.
Phase 3: Duration Of Response (DoR) as assessed by BICR
DoR defined as time from the first documented CR or PR to the first occurrence of radiographic progression per RECIST v1.1 or death from any cause, whichever occurs first. DoR is defined for subjects with confirmed CR/PR.
Phase 3: Disease Control (DC) as assessed by BICR:
DC is defined as best overall response of confirmed CR or confirmed PR, or stable disease (SD) based on RECIST, v1.1
Phase 3: Change from baseline in the EORCT QLQ-C30 physical functioning domain at Week 13
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales, 3 symptom scales, a global health status/QoL scale, and 6 single items. Participants rate items on a 4-point scale ranging from 1 (not at all) to 4 (very much).
