CRC is the third most common type of cancer diagnosed worldwide with developed countries at highest risk. The purpose of this study is to assess adverse events and change in disease activity when telisotuzumab adizutecan is given in combination with oxaliplatin, fluorouracil (5FU), leucovorin (LV) (FOLFOX), and bevacizumab or panitumumab.
Telisotuzumab adizutecan is an investigational drug being developed for the treatment of mCRC. Fluorouracil and leucovorin are drugs approved for the treatment of mCRC. This study will be divided into two stages, with the first stage treating participants with increasing doses of telisotuzumab adizutecan with FOLFOX and bevacizumab or 5FU/LV and panitumumab until the dose reached is tolerable and expected to be efficacious. Participants will then be randomized into 3 groups called treatment arms where one group will receive one of two optimized doses of telisotuzumab adizutecan from the dose escalation phase with FOLFOX and bevacizumab or 5FU/LV and panitumumab, or a comparator of FOLFOX and bevacizumab or panitumumab. Approximately 390 adult participants with mCRC will be enrolled in the study in 100 sites worldwide.
In the dose escalation stage participants will be treated with increasing intravenous (IV) doses of telisotuzumab adizutecan with FOLFOX and bevacizumab or 5FU/LV and panitumumab until the dose reached is tolerable and expected to be efficacious. In the dose optimization stage participants will be receive FOLFOX or receive 5FU/LV, but with one of two optimized doses of telisotuzumab adizutecan, or a comparator of FOLFOX and bevacizumab/pantitumumab. The study will run for a duration of approximately 6 years.
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.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Laboratory values meeting the criteria within the protocol.
Has measurable disease per response evaluation criteria in solid tumors (RECIST) v1.1.
Prior systemic regimen containing c-Met targeting agent(s) (e.g., antibody, antibody drug conjugate, bispecific) and/or any topoisomerase inhibitor(s) (e.g., irinotecan).
History of other malignancies within 5 years prior to screening, except for malignancies with a negligible risk of metastasis or death.
Parallel
Telisotuzumab Adizutecan
DrugIntravenous (IV) Infusion
Fluorouracil
DrugIV Infusion; IV Injection
Oxaliplatin
DrugIV Infusion
Leucovorin
DrugIV Infusion; IV Injection
Bevacizumab
DrugIV Infusion
Panitumumab
DrugIV Infusion
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Treatment groupsSee each treatment group below.
Objective Response (OR) as Assessed by the Investigator confirmed complete response (CR) or partial response (PR) as assessed by the investigator per response evaluation criteria in solid tumors (RECIST), version 1.1.
OR is defined as confirmed CR or PR as assessed by the investigator per RECIST, version 1.1.
Number of Participants with Adverse Events (AE)s
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Progression-Free Survival (PFS) as Assessed by the Investigator
PFS is defined as the time from the first dose of study treatment to the first occurrence of radiographic progression based on RECIST version 1.1 as determined by the investigator or death from any cause, whichever occurs earlier.
Duration of Response (DOR) as Assessed by the investigator
DOR is defined as the time from the first documented CR or PR to the first occurrence of radiographic progression per RECIST v1.1 as determined by the investigator or death from any cause, whichever occurs first.
Overall Survival (OS)
OS is defined as the time from first dose of study treatment to the event of death from any cause.
Disease Control (DC) as Assessed by the Investigator
DC is defined as best overall response of confirmed CR or confirmed PR, or stable disease (SD) based on RECIST, version 1.1 as determined by the investigator.