Clinical trial NCT06614192: 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
Official title: AndroMETa-CRC-064: An Open Label, Randomized, Controlled, Global Phase 3 Study Comparing ABBV-400 Monotherapy to LONSURF (Trifluridine and Tipiracil) Plus Bevacizumab in Subjects With c-Met Over-Expressed Refractory Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Metastatic Colorectal Cancer
ABBV-400
Trifluridine
Tipiracil
LONSURF
Bevacizumab
AndroMETa-CRC-064
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2024-09-26
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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.

Primary outcomes:
measure: Stage 1: Percentage of Participants with Adverse Events (AE)s
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: Percentage of Participants with Clinically Significant Vital Sign Measurements as Assessed by the Investigator
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: Percentage of Participants with Clinically Significant Electrocardiograms (ECGs) Findings as Assessed by the Investigator
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: Percentage of Participants with Clinically Significant Laboratory Values (Chemistry, Hematology, Coagulation, and Urinalysis) as Assessed by the Investigator
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1 and Stage 2: Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: Up to a Maximum of 4 Years
measure: Stage 2: Overall Survival (OS)
timeFrame: Up to a Maximum of 4 Years
Secondary outcomes:
measure: Stage 1 and Stage 2: Progression Free Survival (PFS) as Assessed by BICR
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: OS
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1 and Stage 2: Duration of Response (DOR) as Assessed by BICR
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1 and Stage 2: Disease Control (DC) as Assessed by BICR
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1 and Stage 2: OR as Assessed by Investigator
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1 and Stage 2: PFS as Assessed by Investigator
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1 and Stage 2: DOR as Assessed by Investigator
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: Maximum Observed Serum (or Plasma, for Payload) Concentration (Cmax) for ABBV-400
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: Time to Cmax (Tmax) for ABBV-400
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: Terminal Elimination Half-Life (t1/2) for ABBV-400
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: Area Under the Serum (or Plasma, for Payload) Concentration Versus Time Curve (AUC) for ABBV-400
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: Antibody Drug Conjugate (ADC) for ABBV-400
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: Unconjugated Topoisomerase 1 (Top1) Inhibitor Payload for ABBV-400
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: Incidence of Anti-Drug Antibodies (ADAs) for ABBV-400
timeFrame: Up to a Maximum of 4 Years
measure: Stage 1: Neutralizing Anti-Drug Antibodies (nADAs) for ABBV-400
timeFrame: Up to a Maximum of 4 Years
measure: 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)
timeFrame: Up to a Maximum of 4 Years
measure: 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
timeFrame: Up to a Maximum of 4 Years
measure: 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
timeFrame: Up to a Maximum of 4 Years
measure: Stage 2: Change from Baseline at C7D1 (SOC Arm) in Diarrhea as Measured by the Physical Functioning Domain of the EORTC QLQ-C30
timeFrame: Up to a Maximum of 4 Years
measure: 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
timeFrame: Up to a Maximum of 4 Years
measure: Stage 2: Change from Baseline at C7D1 (SOC Arm) in GHS/QoL as Measured by the Physical Functioning Domain of the EORTC QLQ-C30
timeFrame: Up to a Maximum of 4 Years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center /ID# 267875
state: California
city: Irvine
country: United States
facility: City of Hope Orange County Lennar Foundation Cancer Center /ID# 270655
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center /ID# 268131
state: California
city: Golden
country: United States
facility: Lutheran Medical Center- Cancer Centers of Colorado /ID# 268175
state: Colorado
city: New Haven
country: United States
facility: Yale New Haven Hospital /ID# 269125
state: Connecticut
city: Orlando
country: United States
facility: AdventHealth Orlando /ID# 267970
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University /ID# 266884
state: Georgia
city: Boise
country: United States
facility: St. Luke's Cancer Institute: Boise /ID# 268095
state: Idaho
city: Chicago
country: United States
facility: Northwestern University Robert H. Lurie Comprehensive Cancer Center /ID# 268610
state: Illinois
city: Hinsdale
country: United States
facility: Hope And Healing Cancer Services /ID# 268541
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic /ID# 268666
state: Illinois
city: Indianapolis
country: United States
facility: Community Cancer Center North /ID# 267965
state: Indiana
city: Hattiesburg
country: United States
facility: Hattiesburg Clinic /ID# 267860
state: Mississippi
city: Saint Louis
country: United States
facility: Washington University /ID# 267872
state: Missouri
city: Billings
country: United States
facility: Intermountain Health St. Vincent Regional Hospital - Cancer Centers of Montana /ID# 268185
state: Montana
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey /ID# 268056
state: New Jersey
city: Chapel Hill
country: United States
facility: University of North Carolina Medical Center /ID# 266879
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center /ID# 267966
state: North Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute - Sioux Falls /ID# 268074
state: South Dakota
city: Germantown
country: United States
facility: West Cancer Center and Research Institute - Germantown /ID# 268619
state: Tennessee
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center /ID# 268098
state: Texas
city: Houston
country: United States
facility: Millennium Research & Clinical Development /ID# 268400
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia /ID# 268108
state: Virginia
city: South Brisbane
country: Australia
facility: Mater Hospital Brisbane /ID# 268360
state: Queensland
city: Haifa
country: Israel
facility: Rambam Health Care Campus /ID# 267739
state: H_efa
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center /ID# 267741
state: Tel-Aviv
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center /ID# 267578
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center-Hebrew University /ID# 267579
city: Petah Tikva
country: Israel
facility: Rabin Medical Center /ID# 267740
city: Tel Aviv
country: Israel
facility: Assuta Medical Center /ID# 267745
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center /ID# 268237
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 268236
state: Chiba
city: Suita-shi
country: Japan
facility: The University of Osaka Hospital /ID# 268743
state: Osaka
city: Kitaadachi-gun
country: Japan
facility: Saitama Cancer Center /ID# 268706
state: Saitama
city: Chuo-Ku
country: Japan
facility: National Cancer Center Hospital /ID# 268713
state: Tokyo
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital /ID# 268592
state: Gyeonggido
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital /ID# 268719
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System Severance Hospital /ID# 268718
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 268717
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center /ID# 268720
state: Seoul Teugbyeolsi
city: Rio Piedras
country: Puerto Rico
facility: Pan American Center for Oncology Trials /ID# 267888
city: Kaohsiung City
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital /ID# 267638
state: Kaohsiung
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital /ID# 267627
state: Taipei
city: Changhua City, Changhua County
country: Taiwan
facility: Changhua Christian Hospital /ID# 270464
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 267635
city: Taichung
country: Taiwan
facility: China Medical University Hospital /ID# 267631
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital /ID# 270467
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital /ID# 270468
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital /ID# 267628
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital /ID# 267637
Study officials:
affiliation: AbbVie
name: ABBVIE INC.
role: STUDY_DIRECTOR
References: