Metastatic Colorectal Cancer
Conditions
Keywords
Metastatic Colorectal Cancer, Telisotuzumab Adizutecan, ABBV-400, Trifluridine, Tipiracil, LONSURF, Bevacizumab, AndroMETa-CRC-064
Brief summary
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.
Interventions
Intravenous (IV) Infusion
DRUGTrifluridine/Tipiracil
Oral Tablet
DRUGBevacizumab
IV Infusion
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Life expectancy \>= 12 weeks per investigator assessment. * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 during the screening period prior to the first dose of the study drug. * Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
Exclusion criteria
* Prior systemic regimen containing c-MET targeting antibody/bispecific or Antibody Drug Conjugate (c-Met targeting Antibody Drug Conjugate \[ADC\]). * History of allergic reactions or hypersensitivity to bevacizumab or any of its excipients, or to compounds similar to trifluridine/tipiracil. * Active infection as noted in the protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1: Percentage of Participants with Adverse Events (AE)s | Up to a Maximum of 4 Years | 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. |
| Stage 1: Percentage of Participants with Clinically Significant Vital Sign Measurements as Assessed by the Investigator | Up to a Maximum of 4 Years | 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. |
| Stage 1: Percentage of Participants with Clinically Significant Electrocardiograms (ECGs) Findings as Assessed by the Investigator | Up to a Maximum of 4 Years | Percentage of participants with clinically significant ECGs findings as assessed by the investigator. |
| Stage 1: Percentage of Participants with Clinically Significant Laboratory Values (Chemistry, Hematology, Coagulation, and Urinalysis) as Assessed by the Investigator | Up to a Maximum of 4 Years | Percentage of participants with clinically significant laboratory values (hematology, chemistry, coagulation, and urinalysis) as assessed by the investigator. |
| Stage 1 and Stage 2: Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR) | Up to a Maximum of 4 Years | 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. |
| Stage 2: Overall Survival (OS) | Up to a Maximum of 4 Years | OS is defined as the time from randomization to the event of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stage 1 and Stage 2: DOR as Assessed by Investigator | Up to a Maximum of 4 Years | 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. |
| Stage 1: Maximum Observed Serum (or Plasma, for Payload) Concentration (Cmax) for Telisotuzumab Adizutecan | Up to a Maximum of 4 Years | Maximum observed serum (or plasma, for payload) concentration for telisotuzumab adizutecan. |
| Stage 1: Time to Cmax (Tmax) for Telisotuzumab Adizutecan | Up to a Maximum of 4 Years | Time to Cmax for telisotuzumab adizutecan. |
| Stage 1: Terminal Elimination Half-Life (t1/2) for Telisotuzumab Adizutecan | Up to a Maximum of 4 Years | Terminal elimination half-life for telisotuzumab adizutecan. |
| Stage 1: Area Under the Serum (or Plasma, for Payload) Concentration Versus Time Curve (AUC) for Telisotuzumab Adizutecan | Up to a Maximum of 4 Years | Area under the serum (or plasma, for payload) concentration versus time curve will be determined using noncompartmental methods for total antibody for telisotuzumab adizutecan. |
| Stage 1: Antibody Drug Conjugate (ADC) for Telisotuzumab Adizutecan | Up to a Maximum of 4 Years | Antibody drug conjugate for telisotuzumab adizutecan. |
| Stage 1: Unconjugated Topoisomerase 1 (Top1) Inhibitor Payload for Telisotuzumab Adizutecan | Up to a Maximum of 4 Years | Unconjugated Top1 inhibitor payload for telisotuzumab adizutecan. |
| Stage 1 and Stage 2: Progression Free Survival (PFS) as Assessed by BICR | Up to a Maximum of 4 Years | 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. |
| Stage 1: Neutralizing Anti-Drug Antibodies (nADAs) for Telisotuzumab Adizutecan | Up to a Maximum of 4 Years | Neutralizing anti-drug antibodies for telisotuzumab adizutecan. |
| 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) | Up to a Maximum of 4 Years | 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). |
| 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 | Up to a Maximum of 4 Years | 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). |
| Stage 2: Change from Baseline at C5D1 in in Diarrhea as Measured by the Physical Functioning Domain of the EORTC QLQ-C30 | Up to a Maximum of 4 Years | 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). |
| Stage 2: Change from Baseline at C7D1 (SOC Arm) in Diarrhea as Measured by the Physical Functioning Domain of the EORTC QLQ-C30 | Up to a Maximum of 4 Years | 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). |
| 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 | Up to a Maximum of 4 Years | 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). |
| Stage 2: Change from Baseline at C7D1 (SOC Arm) in GHS/QoL as Measured by the Physical Functioning Domain of the EORTC QLQ-C30 | Up to a Maximum of 4 Years | 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). |
| Stage 1: Incidence of Anti-Drug Antibodies (ADAs) for Telisotuzumab Adizutecan | Up to a Maximum of 4 Years | Incidence of anti-drug antibodies for telisotuzumab adizutecan. |
| Stage 1: OS | Up to a Maximum of 4 Years | OS is defined as the time from randomization to the event of death from any cause |
| Stage 1 and Stage 2: Duration of Response (DOR) as Assessed by BICR | Up to a Maximum of 4 Years | 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. |
| Stage 1 and Stage 2: Disease Control (DC) as Assessed by BICR | Up to a Maximum of 4 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 BICR. |
| Stage 1 and Stage 2: OR as Assessed by Investigator | Up to a Maximum of 4 Years | OR is defined as confirmed CR or confirmed PR as assessed by investigator per RECIST, version 1.1. |
| Stage 1 and Stage 2: PFS as Assessed by Investigator | Up to a Maximum of 4 Years | 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. |
Countries
Australia, Israel, Japan, Puerto Rico, South Korea, Taiwan, United States
Contacts
Primary ContactABBVIE CALL CENTER
Outcome results
None listed