Colorectal cancer (CRC) is the third most common type of cancer diagnosed worldwide and in China. The purpose of this study is to assess adverse events disease activity when comparing intravenously (IV) infused telisotuzumab adizutecan to trifluridine and tipiracil (LONSURF) oral tablets plus IV infused bevacizumab in adult participants with c-Met protein above cutoff level refractory metastatic colorectal cancer (mCRC). Telisotuzumab adizutecan is an investigational drug being developed for the treatment of CRC. Participants are put into treatment arms as part of 2 stages. Each treatment arm in stage 1 receives a different dose of telisotuzumab adizutecan. Each treatment arm in stage 2 receives the optimal dose of telisotuzumab adizutecan or LONSURF plus bevacizumab. Up to approximately 460 adult participants with c-Met protein above cutoff level refractory mCRC, will be enrolled in the study in approximately 160 sites in 15-20 countries. In stage 1, participants will receive intravenously (IV) infused telisotuzumab adizutecan dose A or B. In stage 2, participants will receive the optimal dose of IV infused telisotuzumab adizutecan or the standard of care (SOC), LONSURF oral tablets plus IV infused bevacizumab. The total study duration will be approximately 4 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
460
City of Hope National Medical Center /ID# 267875
Duarte, California, United States
RECRUITINGCity of Hope - Orange County Lennar Foundation Cancer Center /ID# 270655
Irvine, California, United States
RECRUITINGUSC Norris Comprehensive Cancer Center /ID# 268131
Los Angeles, California, United States
RECRUITINGLutheran Medical Center- Cancer Centers of Colorado /ID# 268175
Golden, Colorado, United States
Stage 1: Percentage of Participants with Adverse Events (AE)s
An AE is defined as any untoward medical occurrence, inappropriate patient management decision, unintended disease or injury or any untoward clinical signs (including an abnormal laboratory finding) in participants, users or other persons whether or not related to the investigational drug.
Time frame: Up to a Maximum of 4 Years
Stage 1: Percentage of Participants with Clinically Significant Vital Sign Measurements as Assessed by the Investigator
Vital signs are defined as determinations of systolic and diastolic blood pressure, pulse rate, respiratory rate, oxygen saturation (SpO2), and body temperature will be obtained at visits.
Time frame: Up to a Maximum of 4 Years
Stage 1: Percentage of Participants with Clinically Significant Electrocardiograms (ECGs) Findings as Assessed by the Investigator
Percentage of participants with clinically significant ECGs findings as assessed by the investigator.
Time frame: Up to a Maximum of 4 Years
Stage 1: Percentage of Participants with Clinically Significant Laboratory Values (Chemistry, Hematology, Coagulation, and Urinalysis) as Assessed by the Investigator
Percentage of participants with clinically significant laboratory values (hematology, chemistry, coagulation, and urinalysis) as assessed by the investigator.
Time frame: Up to a Maximum of 4 Years
Stage 1 and Stage 2: Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR)
OR is defined as confirmed complete response (CR) or confirmed partial response (PR) as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
Time frame: Up to a Maximum of 4 Years
Stage 2: Overall Survival (OS)
OS is defined as the time from randomization to the event of death from any cause.
Time frame: Up to a Maximum of 4 Years
Stage 1 and Stage 2: Progression Free Survival (PFS) as Assessed by BICR
PFS is defined as the time from randomization to the first occurrence of radiographic progression based on RECIST version 1.1 as determined by BICR or death from any cause, whichever occurs earlier.
Time frame: Up to a Maximum of 4 Years
Stage 1: OS
OS is defined as the time from randomization to the event of death from any cause
Time frame: Up to a Maximum of 4 Years
Stage 1 and Stage 2: Duration of Response (DOR) as Assessed by BICR
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 BICR or death from any cause, whichever occurs first. DOR is defined for participants with confirmed CR/PR.
Time frame: Up to a Maximum of 4 Years
Stage 1 and Stage 2: 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, version 1.1 as determined by BICR.
Time frame: Up to a Maximum of 4 Years
Stage 1 and Stage 2: OR as Assessed by Investigator
OR is defined as confirmed CR or confirmed PR as assessed by investigator per RECIST, version 1.1.
Time frame: Up to a Maximum of 4 Years
Stage 1 and Stage 2: PFS as Assessed by Investigator
PFS is defined as the time from randomization to the first occurrence of radiographic progression based on RECIST version 1.1 as determined by investigator or death from any cause, whichever occurs earlier.
Time frame: Up to a Maximum of 4 Years
Stage 1 and Stage 2: DOR as Assessed by 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 BICR or death from any cause, whichever occurs first. DOR is defined for participants with confirmed CR/PR.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Yale New Haven Hospital /ID# 269125
New Haven, Connecticut, United States
RECRUITINGAdventHealth Orlando /ID# 267970
Orlando, Florida, United States
RECRUITINGWinship Cancer Institute of Emory University /ID# 266884
Atlanta, Georgia, United States
RECRUITINGSt. Luke's Cancer Institute: Boise /ID# 268095
Boise, Idaho, United States
RECRUITINGNorthwestern Memorial Hospital /ID# 268610
Chicago, Illinois, United States
RECRUITINGHope And Healing Cancer Services /ID# 268541
Hinsdale, Illinois, United States
RECRUITING...and 41 more locations
Time frame: Up to a Maximum of 4 Years
Stage 1: Maximum Observed Serum (or Plasma, for Payload) Concentration (Cmax) for Telisotuzumab Adizutecan
Maximum observed serum (or plasma, for payload) concentration for telisotuzumab adizutecan.
Time frame: Up to a Maximum of 4 Years
Stage 1: Time to Cmax (Tmax) for Telisotuzumab Adizutecan
Time to Cmax for telisotuzumab adizutecan.
Time frame: Up to a Maximum of 4 Years
Stage 1: Terminal Elimination Half-Life (t1/2) for Telisotuzumab Adizutecan
Terminal elimination half-life for telisotuzumab adizutecan.
Time frame: Up to a Maximum of 4 Years
Stage 1: Area Under the Serum (or Plasma, for Payload) Concentration Versus Time Curve (AUC) for Telisotuzumab Adizutecan
Area under the serum (or plasma, for payload) concentration versus time curve will be determined using noncompartmental methods for total antibody for telisotuzumab adizutecan.
Time frame: Up to a Maximum of 4 Years
Stage 1: Antibody Drug Conjugate (ADC) for Telisotuzumab Adizutecan
Antibody drug conjugate for telisotuzumab adizutecan.
Time frame: Up to a Maximum of 4 Years
Stage 1: Unconjugated Topoisomerase 1 (Top1) Inhibitor Payload for Telisotuzumab Adizutecan
Unconjugated Top1 inhibitor payload for telisotuzumab adizutecan.
Time frame: Up to a Maximum of 4 Years
Stage 1: Incidence of Anti-Drug Antibodies (ADAs) for Telisotuzumab Adizutecan
Incidence of anti-drug antibodies for telisotuzumab adizutecan.
Time frame: Up to a Maximum of 4 Years
Stage 1: Neutralizing Anti-Drug Antibodies (nADAs) for Telisotuzumab Adizutecan
Neutralizing anti-drug antibodies for telisotuzumab adizutecan.
Time frame: Up to a Maximum of 4 Years
Stage 2: Change from Baseline at C5D1 in Physical Functioning as Measured by the Physical Functioning Domain of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/Quality of Life (QoL) scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).
Time frame: Up to a Maximum of 4 Years
Stage 2: Change from Baseline at C7D1 (Standard of Care [SOC] Arm) in Physical Functioning as Measured by the Physical Functioning Domain of the EORTC QLQ-C30
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).
Time frame: Up to a Maximum of 4 Years
Stage 2: Change from Baseline at C5D1 in in Diarrhea as Measured by the Physical Functioning Domain of the EORTC QLQ-C30
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/Quality of Life (QoL) scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).
Time frame: Up to a Maximum of 4 Years
Stage 2: Change from Baseline at C7D1 (SOC Arm) in Diarrhea as Measured by the Physical Functioning Domain of the EORTC QLQ-C30
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).
Time frame: Up to a Maximum of 4 Years
Stage 2: Change from Baseline at C5D1 in in Global Health Status (GHS)/QoL as Measured by the Physical Functioning Domain of the EORTC QLQ-C30
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/Quality of Life (QoL) scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).
Time frame: Up to a Maximum of 4 Years
Stage 2: Change from Baseline at C7D1 (SOC Arm) in GHS/QoL as Measured by the Physical Functioning Domain of the EORTC QLQ-C30
The EORTC QLQ-C30 is a 30-item patient-reported questionnaire composed of both multi-item and single scales including 5 functional scales (physical, role, emotional, social, and cognitive), 3 symptom scales (fatigue, nausea and vomiting, and pain), a global health status/QoL scale, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale ranging from 1 to 4 (1 = Not at All, 2 = A Little, 3 = Quite a Bit, and 4 = Very Much).
Time frame: Up to a Maximum of 4 Years