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A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer

NCT05379595 · Janssen Research & Development, LLC
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Official title
A Phase 1b/2, Open-Label Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer
About this study
Colorectal cancer (CRC) is a major global health concern and the third most common cancer worldwide. Amivantamab (also known as RYBREVANT or JNJ-61186372) is a fully human immunoglobulin (Ig) G1-based bispecific antibody (Ab) directed against the epidermal growth factor (EGF) and mesenchymal epithelial transition (MET) receptors, with evidence of preclinical activity against non-small cell lung cancer (NSCLC) tumors with activating EGF receptor (EGFR) mutations, the T790M and C797S second-site resistance EGFR mutations, overexpressed wild-type EGFR, as well as with activation of the MET pathway. Amivantamab has demonstrated activity in both EGFR- and MET-driven NSCLC, with preclinical evidence demonstrating its ability to recruit immune effector cells. While two anti-EGFR antibodies are incorporated as part of the SoC for CRC patients, MET is highly expressed or amplified in subsets of CRC and additionally plays a role in mediating resistance to anti-EGFR treatments. The study consists of up to 28 days screening period, treatment period will begin on Cycle 1 Day 1 (C1D1) (for Cohorts A, B, and C) or C1D -2 (for Ph1b-D, Ph1b-E, Cohorts D, E and F) with the administration of the study treatment and continue as 28-day cycles until the end of treatment visit, up to 30 days after discontinuation of study treatment. The safety of amivantamab as a monotherapy or in addition to SoC chemotherapy will be assessed by physical examinations, Eastern Cooperative Oncology Group (ECOG) criteria for performance status (PS), laboratory tests, vital signs, monitoring of adverse events, and concomitant medication usage.
Eligibility criteria
Inclusion Criteria: * Participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum * Participant must have tumor previously characterized as having wild-type Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), and without evidence of Erb-b2 receptor tyrosine kinase 2/human epidermal growth factor receptor 2 (ERBB2/HER2) amplification. Additional cohort-specific requirements: * Phase (Ph) 2 (Cohorts A, B, and C) Amivantamab monotherapy: Participant must have received at least 2 but not more than 3 prior lines of systemic therapy in the metastatic setting. Participant must have been diagnosed with left-sided colorectal cancer (CRC) (Cohort A and B) and right-sided (Cohort C)and have received or been intolerant to standard of care (SoC) fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy and an anti-vascular endothelial growth factor (VEGF) treatment. Participant must be anti-EGFR treatment naive in Cohort A, an anti-epidermal growth factor receptor (EGFR) treatment Cohort B, with or without an anti-EGFR treatment in Cohort C * Ph 1b Dose Confirmation Cohorts (Ph1b-D and Ph1b-E), Ph2 (Cohorts D and E) Amivantamab+mFOLFOX6/FOLFIRI: Participant must been diagnosed with CRC and have received no more than 1 prior line of systemic therapy in the metastatic setting. Cohort Ph1b-D/Cohort D: Participant must be anti-EGFR treatment naïve, have not received oxaliplatin-based chemotherapy in the metastatic setting, and be eligible for treatment with mFOLFOX6 according to local regulatory approvals and SoC guidelines. Cohort Ph1b-E/Cohort E: Participant must be anti-EGFR treatment naïve, have not received irinotecan-based chemotherapy in the metastatic setting, and be eligible for treatment with FOLFIRI according to local regulatory approvals and SoC guidelines * Ph2 Cohorts F Amivantamab subcutaneous (SC) + mFOLFOX6: Participants must be treatment-naive for right-sided unresectable or metastatic CRC and be eligible for treatment with mFOLFOX6 according to local regulatory approvals and SoC guidelines * For Phase 1 dose confirmation cohorts (Cohorts Ph1b-D and Ph1b-E): Participant must have evaluable disease. For Phase 2: Participant must have measurable disease according to Response Criteria in Solid Tumors (RECIST) Version 1.1. If only one measurable lesion exists, it may be used for the screening biopsy as long as baseline tumor assessment scans are performed greater than or equal to (\>=) 7 days after the biopsy * Participant must have Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1 * Participant must have a tumor lesion amenable for biopsy and agree to mandatory protocol-defined screening biopsy. Biopsies are required if clinically feasible for participants in Ph1b-D, Ph1b-E, and Cohort F. For Cohort F, archival tissue is required if a fresh biopsy is not feasible * A female participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study. Note: Participant must not be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study Exclusion Criteria: * Cohorts A, B, C, Ph1b-D, D, Ph1b-E, and E: Participant with identified mutation in Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), v-raf murine sarcoma viral oncogene homolog B (BRAF), or epidermal growth factor receptor (EGFR) ectodomain, or ERBB2/HER2 amplification by central circulating tumor deoxyribonucleic acid (ctDNA) testing at screening; Cohort F: Participant with identified mutation in KRAS, NRAS, BRAF V600, or PTEN, identified fusions in ALK, ROS-1, RET, and NTRK 1, ERBB2/HER2 amplification, or identified to have MSI-H status by central ctDNA testing at screening * Participant with symptomatic or untreated brain metastasis * History or known presence of leptomeningeal disease * Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (for example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
Study design
Enrollment target: 225 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2022-07-29
Estimated completion: 2030-10-31
Last updated: 2026-04-13
Interventions
Biological: Amivantamab IVBiological: FluorouracilBiological: LeucovorinBiological: OxaliplatinBiological: IrinotecanBiological: Amivantamab
Primary outcomes
  • Cohorts A, B, and C: Objective Response Rate (ORR) (Up to 4 years 3 months)
  • Cohorts Ph1b-D and Ph1b-E: Number of Participants with Dose-limiting Toxicity (DLT) (Up to 4 years 3 months)
  • Cohorts Ph1b-D and Ph1b-E: Number of Participants with DLT by Severity (Up to 4 years 3 months)
Sponsor
Janssen Research & Development, LLC · industry
Contacts & investigators
ContactStudy Contact · contact · Participate-In-This-Study1@its.jnj.com · 844-434-4210
InvestigatorJanssen Research & Development, LLC Clinical Trial · study_director, Janssen Research & Development, LLC
All locations (53)
O Neal Comprehensive Cancer Center at UABRecruiting
Birmingham, Alabama, United States
University of Southern CaliforniaCompleted
Los Angeles, California, United States
University of California, Los Angeles UCLARecruiting
Los Angeles, California, United States
Georgetown University HospitalRecruiting
Washington D.C., District of Columbia, United States
H Lee Moffitt Cancer CenterCompleted
Tampa, Florida, United States
University of Maryland School of MedicineCompleted
Baltimore, Maryland, United States
University of Michigan Health SystemRecruiting
Ann Arbor, Michigan, United States
Start MidwestRecruiting
Grand Rapids, Michigan, United States
Hattiesburg ClinicRecruiting
Hattiesburg, Mississippi, United States
NYU Langone Long Island Clinical Research AssociatesRecruiting
New York, New York, United States
Herbert Irving Comprehensive Cancer Center Columbia University Medical CenterRecruiting
New York, New York, United States
Stephenson Cancer CenterRecruiting
Oklahoma City, Oklahoma, United States
Vanderbilt Ingram Cancer CenterRecruiting
Nashville, Tennessee, United States
MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
Institut Jules BordetRecruiting
Anderlecht, Belgium
Cliniques Universitaires Saint LucRecruiting
Brussels, Belgium
UZ AntwerpenRecruiting
Edegem, Belgium
Universitair Ziekenhuis GasthuisbergRecruiting
Leuven, Belgium
BC Cancer Agency - Vancouver BCRecruiting
Vancouver, British Columbia, Canada
The Ottawa Hospital Cancer CentreRecruiting
Ottawa, Ontario, Canada
Princess Margaret Cancer Centre University Health NetworkRecruiting
Toronto, Ontario, Canada
The Second Hospital To Dalian Medical UniversityCompleted
Dalian, China
Sun Yat-sen University - The Sixth Affiliated Hospital Guangdong Gastrointestinal HospitalRecruiting
Guangzhou, China
The Second Affiliated Hospital of Zhejiang University College of MedicineRecruiting
Hangzhou, China
Hubei province tumor hospitalRecruiting
Wuhan, China
Asklepios Klinik AltonaRecruiting
Hamburg, Germany
Ludwig-Maximilians-Universitaet MuenchenRecruiting
Munich, Germany
Fondazione IRCCS Istituto Nazionale dei TumoriRecruiting
Milan, Italy
A O Ospedale Niguarda Ca GrandaRecruiting
Milan, Italy
Azienda Ospedaliero Universitaria PisanaRecruiting
Pisa, Italy
University Malaya Medical CentreRecruiting
Kuala Lumpur, Malaysia
Hospital Umum SarawakRecruiting
Kuching, Malaysia
Beacon Hospital Sdn BhdRecruiting
Petaling Jaya, Malaysia
Ad Vance Medical ResearchRecruiting
Ponce, Puerto Rico
Pan American Center for Oncology Trials LLCRecruiting
Rio Piedras, Puerto Rico
Seoul National University HospitalRecruiting
Seoul, South Korea
Severance Hospital Yonsei University Health SystemRecruiting
Seoul, South Korea
Asan Medical CenterRecruiting
Seoul, South Korea
Samsung Medical CenterRecruiting
Seoul, South Korea
The Catholic University of Korea Seoul St Mary s HospitalRecruiting
Seoul, South Korea
Hosp Univ Vall D HebronRecruiting
Barcelona, Spain
Hosp. Gral. Univ. Gregorio MaranonRecruiting
Madrid, Spain
Hosp. Univ. Ramon Y CajalRecruiting
Madrid, Spain
Hosp Univ Fund Jimenez DiazRecruiting
Madrid, Spain
Hosp Univ Hm SanchinarroRecruiting
Madrid, Spain
Hosp. Univ. Marques de ValdecillaRecruiting
Santander, Spain
Hosp. Clinico Univ. de ValenciaRecruiting
Valencia, Spain
Changhua Christian HospitalRecruiting
Changhua, Taiwan
Kaohsiung Chang Gung Memorial HospitalRecruiting
Kaohsiung City, Taiwan
Chi Mei Medical Center Liu YingRecruiting
Liou Ying Township, Taiwan
National Cheng Kung University HospitalRecruiting
Tainan, Taiwan
National Taiwan University HospitalRecruiting
Taipei, Taiwan
Linkou Chang Gung Memorial HospitalRecruiting
Taoyuan District, Taiwan