A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer (OrigAMI-1)
Last Updated   April 24, 2024 - 21:00
OVERVIEW
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Gender
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Age
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Phase
phase 1Researchers test a new drug or treatment in a small group of people for the first time to gather information on its safety, dosing, and side effects. -
Sites
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Status
Recruiting
SUMMARY
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 and E) 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. The total duration of this study will be up to 4 years 3 months.
CONDITIONS
- Advanced or Metastatic Colorectal Cancer
ELIGIBILITY
Inclusion Criteria:
* Participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum
* For Phase 1 dose confirmation cohorts (Cohorts Ph1b-D and Ph1b-E): Participant must have evaluable disease. For Phase 2 dose expansion cohorts (Cohorts D and E): 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
* 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:
* 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
* 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
DETAILS
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 and E) 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. The total duration of this study will be up to 4 years 3 months.
LOCATIONS
Country (11) | City or Province (53) | Status |
United States | Ann Arbor, MI University of Michigan Health System |
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United States | Baltimore, MD University of Maryland School of Medicine |
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United States | Birmingham, AL O Neal Comprehensive Cancer Center at UAB |
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United States | Grand Rapids, MI Start Midwest |
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United States | Hattiesburg, MS Hattiesburg Clinic |
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United States | Houston, TX MD Anderson Cancer Center |
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United States | Los Angeles, CA University of California, Los Angeles UCLA |
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United States | Los Angeles, CA University of Southern California |
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United States | Nashville, TN Vanderbilt - Ingram Cancer Center |
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United States | New York, NY Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center |
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United States | New York, NY NYU Langone Long Island Clinical Research Associates |
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United States | Oklahoma City, OK Stephenson Cancer Center |
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United States | Tampa, FL H. Lee Moffitt Cancer Center |
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United States | Washington, DC Georgetown University Hospital |
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Taiwan | Changhua Changhua Christian Hospital |
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Taiwan | Kaohsiung Kaohsiung Chang Gung Memorial Hospital |
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Taiwan | Liou Ying Township Chi Mei Medical Center - Liu Ying |
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Taiwan | Tainan National Cheng Kung University Hospital |
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Taiwan | Taipei National Taiwan University Hospital |
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Taiwan | Taoyuan Linkou Chang Gung Memorial Hospital |
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Spain | Barcelona, BA Hosp. Univ. Vall D Hebron |
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Spain | Madrid, MD Hosp. Gral. Univ. Gregorio Maranon |
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Spain | Madrid, MD Hosp. Univ. Fund. Jimenez Diaz |
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Spain | Madrid, MD Hosp. Univ. Hm Sanchinarro |
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Spain | Madrid, MD Hosp. Univ. Ramon Y Cajal |
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Spain | Santander, CT Hosp. Univ. Marques de Valdecilla |
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Spain | Valencia, VC Hosp. Clinico Univ. de Valencia |
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South Korea | Seoul Asan Medical Center |
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South Korea | Seoul Samsung Medical Center |
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South Korea | Seoul Seoul National University Hospital |
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South Korea | Seoul Severance Hospital Yonsei University Health System |
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South Korea | Seoul The Catholic University of Korea Seoul St. Mary's Hospital |
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Puerto Rico | Ponce Ad-Vance Medical Research |
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Puerto Rico | Rio Piedras Pan American Center for Oncology Trials LLC |
RECRUITING
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Malaysia | Kuala Lumpur University Malaya Medical Centre |
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Malaysia | Kuching, SR Hospital Umum Sarawak |
RECRUITING
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Malaysia | Petaling Jaya, SL Beacon Hospital Sdn Bhd |
RECRUITING
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Italy | Milano A O Ospedale Niguarda Ca Granda |
RECRUITING
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Italy | Milano Fondazione IRCCS Istituto Nazionale dei Tumori |
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Italy | Pisa Azienda Ospedaliero Universitaria Pisana |
RECRUITING
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Germany | Hamburg, HH Asklepios Klinik Altona |
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Germany | Munich Ludwig-Maximilians-Universitaet Muenchen |
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China | Da Lian Shi The Second Hospital To Dalian Medical University |
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China | Guangzhou Sun Yat-sen University - The Sixth Affiliated Hospital Guangdong Gastrointestinal Hospital |
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China | Hangzhou The Second Affiliated Hospital of Zhejiang University College of Medicine |
RECRUITING
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China | Wu Han Shi Hubei province tumor hospital |
RECRUITING
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Canada | Ottawa, ON The Ottawa Hospital Cancer Centre |
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Canada | Toronto, ON Princess Margaret Cancer Centre University Health Network |
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Canada | Vancouver, BC BC Cancer Agency - Vancouver BC |
RECRUITING
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Belgium | Anderlecht, BRU Institut Jules Bordet |
RECRUITING
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Belgium | Bruxelles, BRU Cliniques Universitaires Saint Luc |
RECRUITING
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Belgium | Edegem UZ Antwerpen |
RECRUITING
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Belgium | Leuven Universitair Ziekenhuis Gasthuisberg |
RECRUITING
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