A Randomized Trial Assessing Adverse Events and Disease Activity When Comparing Intravenously (IV) Infused ABBV-400 to Trifluridine and Tipiracil (LONSURF) Oral Tablets Plus IV Infused Bevacizumab in Adult Participants With c-Met Over-Expressed Refractory Metastatic Colorectal Cancer
- Conditions
- Metastatic Colorectal Cancer
- Interventions
- Registration Number
- NCT06614192
- Lead Sponsor
- AbbVie
- 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 ABBV-400 to trifluridine and tipiracil (LONSURF) oral tablets plus IV infused bevacizumab in adult participants with c-Met over-expressed refractory metastatic colorectal cancer (mCRC).
ABBV-400 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 ABBV-400. Each treatment arm in stage 2 receives the optimal dose of ABBV-400 or LONSURF plus bevacizumab. Up to approximately 460 adult participants with c-Met over-expressed (OE) 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 ABBV-400 dose A or B. In stage 2, participants will receive the optimal dose of IV infused ABBV-400 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 460
- 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.
- Prior systemic regimen containing c-MET targeting antibody or 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Stage 1: ABBV-400 Dose A ABBV-400 Participants will receive ABBV-400 dose A, as part of the approximately 4 year study duration. Stage 1: ABBV-400 Dose B ABBV-400 Participants will receive ABBV-400 dose B, as part of the approximately 4 year study duration. Stage 2: ABBV-400 Optimal Dose ABBV-400 Participants will receive the optimal dose of ABBV-400, as part of the approximately 4 year study duration. Stage 2: Standard of Care (SOC) Trifluridine/Tipiracil Participants will receive the SOC, as part of the approximately 4 year study duration. Stage 2: Standard of Care (SOC) Bevacizumab Participants will receive the SOC, as part of the approximately 4 year study duration.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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: 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.
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 ABBV-400 Up to a Maximum of 4 Years Maximum observed serum (or plasma, for payload) concentration for ABBV-400.
Stage 1: Time to Cmax (Tmax) for ABBV-400 Up to a Maximum of 4 Years Time to Cmax for ABBV-400.
Stage 1: Terminal Elimination Half-Life (t1/2) for ABBV-400 Up to a Maximum of 4 Years Terminal elimination half-life for ABBV-400.
Stage 1: Area Under the Serum (or Plasma, for Payload) Concentration Versus Time Curve (AUC) for ABBV-400 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 ABBV-400.
Stage 1: Antibody Drug Conjugate (ADC) for ABBV-400 Up to a Maximum of 4 Years Antibody drug conjugate for ABBV-400.
Stage 1: Unconjugated Topoisomerase 1 (Top1) Inhibitor Payload for ABBV-400 Up to a Maximum of 4 Years Unconjugated Top1 inhibitor payload for ABBV-400.
Stage 1: Incidence of Anti-Drug Antibodies (ADAs) for ABBV-400 Up to a Maximum of 4 Years Incidence of anti-drug antibodies for ABBV-400.
Stage 1: Neutralizing Anti-Drug Antibodies (nADAs) for ABBV-400 Up to a Maximum of 4 Years Neutralizing anti-drug antibodies for ABBV-400.
Stage 2: Change from Baseline at C5D1 (ABBV-400 Arm) 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 (ABBV-400 Arm) 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 (ABBV-400 Arm) 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).
Trial Locations
- Locations (50)
Taipei Veterans General Hospital /ID# 267628
🇨🇳Taipei City, Taiwan
Linkou Chang Gung Memorial Hospital /ID# 267637
🇨🇳Taoyuan City, Taiwan
Winship Cancer Institute of Emory University /ID# 266884
🇺🇸Atlanta, Georgia, United States
Yale New Haven Hospital /ID# 269125
🇺🇸New Haven, Connecticut, United States
AdventHealth Orlando /ID# 267970
🇺🇸Orlando, Florida, United States
City of Hope National Medical Center /ID# 267875
🇺🇸Duarte, California, United States
City of Hope Orange County Lennar Foundation Cancer Center /ID# 270655
🇺🇸Irvine, California, United States
USC Norris Comprehensive Cancer Center /ID# 268131
🇺🇸Los Angeles, California, United States
Lutheran Medical Center- Cancer Centers of Colorado /ID# 268175
🇺🇸Golden, Colorado, United States
St. Luke's Cancer Institute: Boise /ID# 268095
🇺🇸Boise, Idaho, United States
Northwestern University Robert H. Lurie Comprehensive Cancer Center /ID# 268610
🇺🇸Chicago, Illinois, United States
Hope And Healing Cancer Services /ID# 268541
🇺🇸Hinsdale, Illinois, United States
Springfield Clinic /ID# 268666
🇺🇸Springfield, Illinois, United States
Community Cancer Center North /ID# 267965
🇺🇸Indianapolis, Indiana, United States
Hattiesburg Clinic /ID# 267860
🇺🇸Hattiesburg, Mississippi, United States
Washington University /ID# 267872
🇺🇸Saint Louis, Missouri, United States
Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana /ID# 268185
🇺🇸Billings, Montana, United States
Rutgers Cancer Institute of New Jersey /ID# 268056
🇺🇸New Brunswick, New Jersey, United States
University of North Carolina Medical Center /ID# 266879
🇺🇸Chapel Hill, North Carolina, United States
Duke University Medical Center /ID# 267966
🇺🇸Durham, North Carolina, United States
Avera Cancer Institute - Sioux Falls /ID# 268074
🇺🇸Sioux Falls, South Dakota, United States
West Cancer Center and Research Institute - Germantown /ID# 268619
🇺🇸Germantown, Tennessee, United States
The University of Texas MD Anderson Cancer Center /ID# 268098
🇺🇸Houston, Texas, United States
Millennium Research & Clinical Development /ID# 268400
🇺🇸Houston, Texas, United States
University of Virginia /ID# 268108
🇺🇸Charlottesville, Virginia, United States
Mater Hospital Brisbane /ID# 268360
🇦🇺South Brisbane, Queensland, Australia
Rambam Health Care Campus /ID# 267739
🇮🇱Haifa, H_efa, Israel
The Chaim Sheba Medical Center /ID# 267741
🇮🇱Ramat Gan, Tel-Aviv, Israel
Tel Aviv Sourasky Medical Center /ID# 267578
🇮🇱Tel Aviv, Tel-Aviv, Israel
Hadassah Medical Center-Hebrew University /ID# 267579
🇮🇱Jerusalem, Israel
Rabin Medical Center /ID# 267740
🇮🇱Petah Tikva, Israel
Assuta Medical Center /ID# 267745
🇮🇱Tel Aviv, Israel
Aichi Cancer Center /ID# 268237
🇯🇵Nagoya-shi, Aichi, Japan
National Cancer Center Hospital East /ID# 268236
🇯🇵Kashiwa-shi, Chiba, Japan
The University of Osaka Hospital /ID# 268743
🇯🇵Suita-shi, Osaka, Japan
Saitama Cancer Center /ID# 268706
🇯🇵Kitaadachi-gun, Saitama, Japan
National Cancer Center Hospital /ID# 268713
🇯🇵Chuo-Ku, Tokyo, Japan
Seoul National University Bundang Hospital /ID# 268592
🇰🇷Seongnam-si, Gyeonggido, Korea, Republic of
Seoul National University Hospital /ID# 268719
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Yonsei University Health System Severance Hospital /ID# 268718
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center /ID# 268717
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Samsung Medical Center /ID# 268720
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Pan American Center for Oncology Trials /ID# 267888
🇵🇷Rio Piedras, Puerto Rico
Kaohsiung Chang Gung Memorial Hospital /ID# 267638
🇨🇳Kaohsiung City, Kaohsiung, Taiwan
National Taiwan University Hospital /ID# 267627
🇨🇳Taipei City, Taipei, Taiwan
Changhua Christian Hospital /ID# 270464
🇨🇳Changhua City, Changhua County, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 267635
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital /ID# 267631
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital /ID# 270467
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital /ID# 270468
🇨🇳Tainan, Taiwan