A Study to Evaluate the Adverse Events, and Efficacy of Intravenous (IV) of Telisotuzumab Adizutecan in Combination With IV Oxaliplatin, Fluorouracil, Folinic Acid/Leucovorin, Bevacizumab, Panitumumab in Adult Participants With Metastatic Colorectal Cancer
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT06820463
- Lead Sponsor
- AbbVie
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 390
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Substudy 1: Dose Escalation Telisotuzumab Adizutecan Fluorouracil Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Escalation Telisotuzumab Adizutecan Oxaliplatin Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Escalation Telisotuzumab Adizutecan Leucovorin Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Escalation Telisotuzumab Adizutecan Bevacizumab Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Telisotuzumab Adizutecan High Dose Telisotuzumab Adizutecan Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Telisotuzumab Adizutecan High Dose Fluorouracil Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Telisotuzumab Adizutecan High Dose Oxaliplatin Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Telisotuzumab Adizutecan High Dose Leucovorin Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Telisotuzumab Adizutecan High Dose Bevacizumab Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Compatator Leucovorin Participants will receive a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Telisotuzumab Adizutecan Low Dose Fluorouracil Participants will receive the low dose of telisotuzumab adizutecandetermined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Telisotuzumab Adizutecan Low Dose Oxaliplatin Participants will receive the low dose of telisotuzumab adizutecandetermined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Telisotuzumab Adizutecan Low Dose Leucovorin Participants will receive the low dose of telisotuzumab adizutecandetermined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Telisotuzumab Adizutecan Low Dose Bevacizumab Participants will receive the low dose of telisotuzumab adizutecandetermined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Compatator Fluorouracil Participants will receive a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Compatator Bevacizumab Participants will receive a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 2: Dose Escalation Telisotuzumab Adizutecan Fluorouracil Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil (5-FU) and leucovorin (LV) and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Escalation Telisotuzumab Adizutecan Leucovorin Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil (5-FU) and leucovorin (LV) and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Escalation Telisotuzumab Adizutecan Panitumumab Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil (5-FU) and leucovorin (LV) and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Telisotuzumab Adizutecan High Dose Telisotuzumab Adizutecan Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Telisotuzumab Adizutecan High Dose Fluorouracil Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Telisotuzumab Adizutecan High Dose Leucovorin Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Telisotuzumab Adizutecan High Dose Panitumumab Participants will receive the high dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Telisotuzumab Adizutecan Low Dose Fluorouracil Participants will receive the low dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Telisotuzumab Adizutecan Low Dose Leucovorin Participants will receive the low dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Telisotuzumab Adizutecan Low Dose Panitumumab Participants will receive the low dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Compatator Fluorouracil Participants will receive a fixed dose of FOLFOX and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Compatator Oxaliplatin Participants will receive a fixed dose of FOLFOX and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Compatator Leucovorin Participants will receive a fixed dose of FOLFOX and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Compatator Panitumumab Participants will receive a fixed dose of FOLFOX and panitumumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Compatator Oxaliplatin Participants will receive a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Escalation Telisotuzumab Adizutecan Telisotuzumab Adizutecan Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil, leucovorin, and oxaliplatin (FOLFOX) and bevacizumab as part of the approximately 6 year study duration. Substudy 1: Dose Expansion Telisotuzumab Adizutecan Low Dose Telisotuzumab Adizutecan Participants will receive the low dose of telisotuzumab adizutecandetermined in the dose expansion arm in combination with a fixed dose of FOLFOX and bevacizumab as part of the approximately 6 year study duration. Substudy 2: Dose Escalation Telisotuzumab Adizutecan Telisotuzumab Adizutecan Participants will receive various doses of telisotuzumab adizutecan in combination with a fixed dose of fluorouracil (5-FU) and leucovorin (LV) and panitumumab as part of the approximately 6 year study duration. Substudy 2: Dose Expansion Telisotuzumab Adizutecan Low Dose Telisotuzumab Adizutecan Participants will receive the low dose of telisotuzumab adizutecan determined in the dose expansion arm in combination with a fixed dose of 5-FU/LV and panitumumab as part of the approximately 6 year study duration.
- Primary Outcome Measures
Name Time Method 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. Up to 24 Weeks 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 Up to Approximately 6 Years 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.
- Secondary Outcome Measures
Name Time Method Disease Control (DC) as Assessed by the Investigator Up to Approximately 6 Years 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.
Progression-Free Survival (PFS) as Assessed by the Investigator Up to 22 Months 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 Up to 14 Months 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) Up to Approximately 6 Years OS is defined as the time from first dose of study treatment to the event of death from any cause.
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Trial Locations
- Locations (10)
Hadassah Medical Center-Hebrew University /ID# 268007
🇮🇱Jerusalem, Israel
Rabin Medical Center /ID# 268008
🇮🇱Petah Tikva, Israel
Yale New Haven Hospital /ID# 270565
🇺🇸New Haven, Connecticut, United States
Tel Aviv Sourasky Medical Center /ID# 268010
🇮🇱Tel Aviv, Tel-Aviv, Israel
Shaare Zedek Medical Center /ID# 268009
🇮🇱Jerusalem, Israel
Pan American Center for Oncology Trials /ID# 268809
🇵🇷Rio Piedras, Puerto Rico
Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 269724
🇨🇳Kaohsiung, Taiwan
Hope And Healing Cancer Services /ID# 271562
🇺🇸Hinsdale, Illinois, United States
Nebraska Cancer Specialists - Omaha - Wright Street /ID# 271646
🇺🇸Omaha, Nebraska, United States
Rambam Health Care Campus /ID# 268006
🇮🇱Haifa, H_efa, Israel