Advanced or Metastatic Colorectal CancerPhase 1/2OrigAMI-1NCT05379595
A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer
A Phase 1/2 study testing Amivantamab IV, Fluorouracil and Leucovorin in people with Advanced or Metastatic Colorectal Cancer, run by Janssen Research & Development, LLC at 53 sites in 11 countries.
Trial summary
The purpose of this study is to assess the anti-tumor activity of amivantamab as a monotherapy (Cohorts A, B, and C), to assess the recommended phase 2 combination dose (RP2CD) of amivantamab when added to SoC chemotherapy (Ph1b cohorts) and to characterize the safety of amivantamab when added to standard-of care… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Colorectal Cancer
- What is being tested?
- Amivantamab IV, Fluorouracil and Leucovorin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 225 participants
- Where
- 53 sitesin 11 countries
- Study dates
- 29 Jul 2022to 11 May 2031
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
53 sites in 11 countries. Contact the study team or a site near you to ask about taking part.
53 sites in 11 countries
United States14 sites, 7 recruiting
- Recruiting
University of Michigan Health System
Ann Arbor, Michigan, 48103
- Completed
University of Maryland School of Medicine
Baltimore, Maryland, 21201
- Completed
O Neal Comprehensive Cancer Center at UAB
Birmingham, Alabama, 35233
- Completed
Start Midwest
Grand Rapids, Michigan, 49546
- Recruiting
Hattiesburg Clinic
Hattiesburg, Mississippi, 39401
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
- Completed
University of Southern California
Los Angeles, California, 90033
- Recruiting
University of California, Los Angeles UCLA
Los Angeles, California, 90404
- Recruiting
Vanderbilt Ingram Cancer Center
Nashville, Tennessee, 37232
- Recruiting
NYU Langone Long Island Clinical Research Associates
New York, New York, 10016
- Recruiting
Herbert Irving Comprehensive Cancer Center Columbia University Medical Center
New York, New York, 10032
- Completed
Stephenson Cancer Center
Oklahoma City, Oklahoma, 73104
- Completed
H Lee Moffitt Cancer Center
Tampa, Florida, 33612
- Completed
Georgetown University Hospital
Washington D.C., District of Columbia, 20007
Spain7 sites, 7 recruiting
- Recruiting
Hosp Univ Vall D Hebron
Barcelona, 08035
- Recruiting
Hosp. Gral. Univ. Gregorio Maranon
Madrid, 28009
- Recruiting
Hosp. Univ. Ramon Y Cajal
Madrid, 28034
- Recruiting
Hosp Univ Fund Jimenez Diaz
Madrid, 28040
- Recruiting
Hosp Univ Hm Sanchinarro
Madrid, 28050
- Recruiting
Hosp. Univ. Marques de Valdecilla
Santander, 39008
- Recruiting
Hosp. Clinico Univ. de Valencia
Valencia, 46010
Taiwan6 sites, 6 recruiting
- Recruiting
Changhua Christian Hospital
Changhua, 500
- Recruiting
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung City, 83301
- Recruiting
Chi Mei Medical Center Liu Ying
Liou Ying Township, 736
- Recruiting
National Cheng Kung University Hospital
Tainan, 704
- Recruiting
National Taiwan University Hospital
Taipei, 10002
- Recruiting
Linkou Chang Gung Memorial Hospital
Taoyuan, 33305
South Korea5 sites, 5 recruiting
- Recruiting
Seoul National University Hospital
Seoul, 03080
- Recruiting
Severance Hospital Yonsei University Health System
Seoul, 03722
- Recruiting
Asan Medical Center
Seoul, 05505
- Recruiting
Samsung Medical Center
Seoul, 06351
- Recruiting
The Catholic University of Korea Seoul St Mary s Hospital
Seoul, 06591
Belgium4 sites, 4 recruiting
- Recruiting
Institut Jules Bordet
Anderlecht, 1070
- Recruiting
Cliniques Universitaires Saint Luc
Brussels, 1200
- Recruiting
UZ Antwerpen
Edegem, 2650
- Recruiting
Universitair Ziekenhuis Gasthuisberg
Leuven, 3000
China4 sites, 3 recruiting
- Completed
The Second Hospital To Dalian Medical University
Dalian, 116023
- Recruiting
Sun Yat-sen University - The Sixth Affiliated Hospital Guangdong Gastrointestinal Hospital
Guangzhou, 510655
- Recruiting
The Second Affiliated Hospital of Zhejiang University College of Medicine
Hangzhou, 310003
- Recruiting
Hubei province tumor hospital
Wuhan, 430079
Canada3 sites, 2 recruiting
- Recruiting
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6
- Recruiting
Princess Margaret Cancer Centre University Health Network
Toronto, Ontario, M5G 1X6
- Completed
BC Cancer Agency - Vancouver BC
Vancouver, British Columbia, V5Z 4E6
Italy3 sites, 3 recruiting
- Recruiting
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133
- Recruiting
A O Ospedale Niguarda Ca Granda
Milan, 20162
- Recruiting
Azienda Ospedaliero Universitaria Pisana
Pisa, 56126
Malaysia3 sites, 3 recruiting
- Recruiting
University Malaya Medical Centre
Kuala Lumpur, 59100
- Recruiting
Hospital Umum Sarawak
Kuching, 93586
- Recruiting
Beacon Hospital Sdn Bhd
Petaling Jaya, 46050
Germany2 sites, 2 recruiting
- Recruiting
Asklepios Klinik Altona
Hamburg, 22763
- Recruiting
Ludwig-Maximilians-Universitaet Muenchen
Munich, 81377
Puerto Rico2 sites, 2 recruiting
- Recruiting
Ad Vance Medical Research
Ponce, 00717
- Recruiting
Pan American Center for Oncology Trials LLC
Rio Piedras, 00935
About this study
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
The purpose of this study is to assess the anti-tumor activity of amivantamab as a monotherapy (Cohorts A, B, and C), to assess the recommended phase 2 combination dose (RP2CD) of amivantamab when added to SoC chemotherapy (Ph1b cohorts) and to characterize the safety of amivantamab when added to standard-of care (SoC) chemotherapy in participants with metastatic colorectal cancer (mCRC) (Ph2 cohorts).
Read the detailed description
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.
- Conditions
- Advanced or Metastatic Colorectal Cancer
- Being tested
- Amivantamab IV, Fluorouracil, Leucovorin, Oxaliplatin, Irinotecan
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Amivantamab IVBiological
Also called RYBREVANT, JNJ-61186372
Amivantamab will be administered as intravenous infusion.
FluorouracilBiological
Fluorouracil will be administered as intravenous infusion.
LeucovorinBiological
Leucovorin will be administered as intravenous infusion.
OxaliplatinBiological
Oxaliplatin will be administered as intravenous infusion.
IrinotecanBiological
Irinotecan will be administered as intravenous infusion.
AmivantamabBiological
Also called JNJ-61186372, RYBREVANT
Amivantamab will be administered.
| Study group | Role | What they receive |
|---|---|---|
| Cohorts A, B, and C: Amivantamab Monotherapy | Experimental | Participants with left-sided colorectal cancer (CRC) in Cohort A (no prior anti-epidermal growth factor receptor [EGFR] therapy) and in Cohort B (post anti-EGFR therapy), and right-sided CRC in Cohort C (with or without anti-EGFR therapy), will be administered intravenous (IV) infusion of amivantamab 1050 milligrams (mg) if body weight (BW) is less than (<) 80 kilograms (kg) or 1400 mg if BW is greater than or equal to (>=) 80 kg, as monotherapy on Days 1 and 15 of Cycle 2 (28-days cycle). Receives: Biological: Amivantamab IV |
| Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) | Active comparator | Participants who are anti-EGFR treatment naïve, have not received oxaliplatin-based chemotherapy in the metastatic setting, will be administered IV infusion of amivantamab 1050 or 700 mg (dose level 0 [DL0]) if BW is <80 kg, or 1400 or 1050 mg (dose de-escalation [DL-1]) if BW is >= 80 kg, on Days -1, -2, 8 and 22 of Cycle 1 and along with mFOLFOX6 SOC chemotherapy on Days 1 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 (each cycle of 28 days) in Phase 1b dose confirmation Cohort (Cohort Ph1b-D). Participant in Phase 2 Cohort (Cohort D) will receive recommended Phase 2 combination dose (RP2CD) of amivantamab along with mFOLFOX6 SOC chemotherapy determined in Cohort Ph1b-D. Receives: Biological: Amivantamab IV; Biological: Fluorouracil; Biological: Leucovorin; Biological: Oxaliplatin |
| Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) | Active comparator | Participants who are anti-EGFR treatment naïve, have not received irinotecan-based chemotherapy in the metastatic setting, will be administered IV infusion of Amivantamab along with FOLFIRI SOC chemotherapy on Days -1, -2, and 8 of Cycle 1 and Days 1 and 15 of Cycle 2 in Ph1b-E. For Cohort E, RP2CD determined in Ph1b-E will be administered. Receives: Biological: Amivantamab IV; Biological: Fluorouracil; Biological: Leucovorin; Biological: Irinotecan |
| Cohort F: Amivantamab + mFOLFOX6 | Active comparator | Participant who are treatment-naïve for right-sided unresectable or metastatic CRC. Participants will receive Amivantamab along with mFOLFOX6 SoC chemotherapy. Receives: Biological: Fluorouracil; Biological: Leucovorin; Biological: Oxaliplatin; Biological: Amivantamab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cohorts A, B, and C: Objective Response Rate (ORR)
ORR is defined as the percentage of participants who achieve either a partial response (PR) or complete response (CR), as defined by investigator assessment using Response Criteria in Solid Tumors (RECIST) version 1.1.
Measured: Up to 4 years 3 months
Cohorts Ph1b-D and Ph1b-E: Number of Participants with Dose-limiting Toxicity (DLT)
Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Measured: Up to 4 years 3 months
Cohorts Ph1b-D and Ph1b-E: Number of Participants with DLT by Severity
Number of participants with DLT by severity will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. Toxicities will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, graded as Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death related to adverse event.
Measured: Up to 4 years 3 months
Cohorts D and E: Number of Participants with Adverse Events (AE)
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the NCI CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening and Grade 5: death related to adverse event.
Measured: Up to 4 years 3 months
Cohorts D and E: Number of Participants with Laboratory Values Abnormalities
Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.
Measured: Up to 4 years 3 months
Cohorts D and E: Number of Participants with Vital Signs Abnormalities
Number of participants with vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and diastolic) and oxygen saturation, abnormalities will be reported.
Measured: Up to 4 years 3 months
Cohorts F: Number of Participants with Adverse Events (AE)
An AE is any untoward medical occurrence in a participant taking part in a in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening and Grade 5: death related to adverse event.
Measured: Up to 4 years 3 months
Cohorts F: Number of Participants with Laboratory Values Abnormalities
Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.
Measured: Up to 4 years 3 months
Cohorts F: Number of Participants with Vital Signs Abnormalities
Number of participants with vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and diastolic) and oxygen saturation, abnormalities will be reported.
Measured: Up to 4 years 3 months
Secondary outcomes (8)
Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with AEs
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the NCI CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening and Grade 5: death related to adverse event.
Measured: Up to 4 years 3 months
Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Laboratory Values Abnormalities
Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.
Measured: Up to 4 years 3 months
Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Vital Signs Abnormalities
Number of participants with vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and diastolic) and oxygen saturation, abnormalities will be reported.
Measured: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: ORR
ORR is defined as the percentage of participants who achieve either a PR or CR, as defined by investigator assessment using RECIST version 1.1.
Measured: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: Duration of Response (DoR)
DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR, as defined by investigator assessment using RECIST version 1.1.
Measured: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: Disease Control Rate (DCR)
DCR is defined as the percentage of participants achieving a best overall response (BOR) of CR, PR or stable disease (with minimum duration of 7 weeks) as defined by RECIST v1.1.
Measured: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants achieving complete or partial response, as well as durable stable disease (defined as a duration of at least 11 weeks) as defined by RECIST version 1.1.
Measured: Up to 4 years 3 months
Cohorts D, E and F: Progression Free Survival (PFS)
PFS is defined as the time from the first administration of study treatment until the date of objective disease progression or death, whichever comes first, based on investigator assessment using RECIST version 1.1.
Measured: Up to 4 years 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2022
- Study start29 Jul 2022
- Primary completion27 Apr 2027 (estimated)
- Study completion11 May 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced or Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 225 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05379595
- Sponsor's protocol ID
- CR109215
- Other IDs
- 61186372GIC2002, 2021-006629-23, 2023-506517-22-00, 2023
- Acronym
- OrigAMI-1
- Status last verified
- Nov 2026
- First submitted
- 17 May 2022
- Last updated
- 3 Nov 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data sharing policy of Johnson \& Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
Publications
Oberstein PE, Hecht JR, Raghav K, Pietrantonio F, Arnold D, Moreno V, Van Cutsem E, Malik RA, Hong YS, Lee MA, Yu-Li Su H, Lee J, Chandana S, Cruz-Correa M, Yuan Y, Ahmad A, Lai KM, Hsu HC, Chen EX, Elez E, Lin CC, Lopez C, Prenen H, Rosello-Keranen S, Velez H, Yeh YM, Heinemann V, Eng C, Beom SH, Tejpar S, Chowdhury S, Lyu X, Kamat M, Curtin JC, Patel B, Xie J, Bhattacharya R, Schnepp RW, Yilmaz E, Iwasawa R, Daksh M, Lorenzini P, Thayu M, Baig M, Kim HS, Han SW. Amivantamab Monotherapy in Chemorefractory RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study. J Clin Oncol. 2026 Jun 10;44(17):1624-1634. doi: 10.1200/JCO-25-02187. Epub 2026 Apr 21.
PubMed 42013403
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05379595
- Acronym / sponsor ID
- OrigAMI-1 / CR109215
- Conditions
- Advanced or Metastatic Colorectal Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 225 participants (estimated)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 29 Jul 2022 (actual)
- Primary completion
- 27 Apr 2027 (estimated)
- Study completion
- 11 May 2031 (estimated)
- First posted
- 18 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to assess the anti-tumor activity of amivantamab as a monotherapy (Cohorts A, B, and C), to assess the recommended phase 2 combination dose (RP2CD) of amivantamab when added to SoC chemotherapy (Ph1b cohorts) and to characterize the safety of amivantamab when added to standard-of care (SoC) chemotherapy in participants with metastatic colorectal cancer (mCRC) (Ph2 cohorts).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohorts A, B, and C: Amivantamab Monotherapy | Experimental | Biological: Amivantamab IVParticipants with left-sided colorectal cancer (CRC) in Cohort A (no prior anti-epidermal growth factor receptor [EGFR] therapy) and in Cohort B (post anti-EGFR therapy), and right-sided CRC in Cohort C (with or without anti-EGFR therapy), will be administered intravenous (IV) infusion of amivantamab 1050 milligrams (mg) if body weight (BW) is less than (<) 80 kilograms (kg) or 1400 mg if BW is greater than or equal to (>=) 80 kg, as monotherapy on Days 1 and 15 of Cycle 2 (28-days cycle). |
| Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) | Active comparator | Biological: Amivantamab IV, Biological: Fluorouracil, Biological: Leucovorin, Biological: OxaliplatinParticipants who are anti-EGFR treatment naïve, have not received oxaliplatin-based chemotherapy in the metastatic setting, will be administered IV infusion of amivantamab 1050 or 700 mg (dose level 0 [DL0]) if BW is <80 kg, or 1400 or 1050 mg (dose de-escalation [DL-1]) if BW is >= 80 kg, on Days -1, -2, 8 and 22 of Cycle 1 and along with mFOLFOX6 SOC chemotherapy on Days 1 and 15 of Cycle 1 and Days 1 and 15 of Cycle 2 (each cycle of 28 days) in Phase 1b dose confirmation Cohort (Cohort Ph1b-D). Participant in Phase 2 Cohort (Cohort D) will receive recommended Phase 2 combination dose (RP2CD) of amivantamab along with mFOLFOX6 SOC chemotherapy determined in Cohort Ph1b-D. |
| Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) | Active comparator | Biological: Amivantamab IV, Biological: Fluorouracil, Biological: Leucovorin, Biological: IrinotecanParticipants who are anti-EGFR treatment naïve, have not received irinotecan-based chemotherapy in the metastatic setting, will be administered IV infusion of Amivantamab along with FOLFIRI SOC chemotherapy on Days -1, -2, and 8 of Cycle 1 and Days 1 and 15 of Cycle 2 in Ph1b-E. For Cohort E, RP2CD determined in Ph1b-E will be administered. |
| Cohort F: Amivantamab + mFOLFOX6 | Active comparator | Biological: Fluorouracil, Biological: Leucovorin, Biological: Oxaliplatin, Biological: AmivantamabParticipant who are treatment-naïve for right-sided unresectable or metastatic CRC. Participants will receive Amivantamab along with mFOLFOX6 SoC chemotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Amivantamab IVAlso: RYBREVANT, JNJ-61186372Amivantamab will be administered as intravenous infusion. | Biological | Cohorts A, B, and C: Amivantamab Monotherapy, Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6), Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) |
| FluorouracilFluorouracil will be administered as intravenous infusion. | Biological | Cohort F: Amivantamab + mFOLFOX6, Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6), Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) |
| LeucovorinLeucovorin will be administered as intravenous infusion. | Biological | Cohort F: Amivantamab + mFOLFOX6, Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6), Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) |
| OxaliplatinOxaliplatin will be administered as intravenous infusion. | Biological | Cohort F: Amivantamab + mFOLFOX6, Cohorts Ph1b-D and D: Amivantamab+5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) |
| IrinotecanIrinotecan will be administered as intravenous infusion. | Biological | Cohorts Ph1b-E and E: Amivantamab+5-Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) |
| AmivantamabAlso: JNJ-61186372, RYBREVANTAmivantamab will be administered. | Biological | Cohort F: Amivantamab + mFOLFOX6 |
Primary outcome
Cohorts A, B, and C: Objective Response Rate (ORR)
Time frame: Up to 4 years 3 months
ORR is defined as the percentage of participants who achieve either a partial response (PR) or complete response (CR), as defined by investigator assessment using Response Criteria in Solid Tumors (RECIST) version 1.1.
Cohorts Ph1b-D and Ph1b-E: Number of Participants with Dose-limiting Toxicity (DLT)
Time frame: Up to 4 years 3 months
Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.
Cohorts Ph1b-D and Ph1b-E: Number of Participants with DLT by Severity
Time frame: Up to 4 years 3 months
Number of participants with DLT by severity will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity. Toxicities will be graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, graded as Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death related to adverse event.
Cohorts D and E: Number of Participants with Adverse Events (AE)
Time frame: Up to 4 years 3 months
An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the NCI CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening and Grade 5: death related to adverse event.
Cohorts D and E: Number of Participants with Laboratory Values Abnormalities
Time frame: Up to 4 years 3 months
Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.
Cohorts D and E: Number of Participants with Vital Signs Abnormalities
Time frame: Up to 4 years 3 months
Number of participants with vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and diastolic) and oxygen saturation, abnormalities will be reported.
Cohorts F: Number of Participants with Adverse Events (AE)
Time frame: Up to 4 years 3 months
An AE is any untoward medical occurrence in a participant taking part in a in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1: mild, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening and Grade 5: death related to adverse event.
Cohorts F: Number of Participants with Laboratory Values Abnormalities
Time frame: Up to 4 years 3 months
Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.
Cohorts F: Number of Participants with Vital Signs Abnormalities
Time frame: Up to 4 years 3 months
Number of participants with vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and diastolic) and oxygen saturation, abnormalities will be reported.
8 secondary outcomes
Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with AEs
Time frame: Up to 4 years 3 months
Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Laboratory Values Abnormalities
Time frame: Up to 4 years 3 months
Cohorts A, B, C, Ph1b-D, and Ph1b-E: Number of Participants with Vital Signs Abnormalities
Time frame: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: ORR
Time frame: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: Duration of Response (DoR)
Time frame: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: Disease Control Rate (DCR)
Time frame: Up to 4 years 3 months
Cohorts Ph1b-D, Ph1b-E, D, E and F: Clinical Benefit Rate (CBR)
Time frame: Up to 4 years 3 months
Cohorts D, E and F: Progression Free Survival (PFS)
Time frame: Up to 4 years 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- Derived from this study: PubMed 42013403Oberstein PE, Hecht JR, Raghav K, Pietrantonio F, Arnold D, Moreno V, Van Cutsem E, Malik RA, Hong YS, Lee MA, Yu-Li Su H, Lee J, Chandana S, Cruz-Correa M, Yuan Y, Ahmad A, Lai KM, Hsu HC, Chen EX, Elez E, Lin CC, Lopez C, Prenen H, Rosello-Keranen S, Velez H, Yeh YM, Heinemann V, Eng C, Beom SH, Tejpar S, Chowdhury S, Lyu X, Kamat M, Curtin JC, Patel B, Xie J, Bhattacharya R, Schnepp RW, Yilmaz E, Iwasawa R, Daksh M, Lorenzini P, Thayu M, Baig M, Kim HS, Han SW. Amivantamab Monotherapy in Chemorefractory RAS/BRAF Wild-Type Metastatic Colorectal Cancer: Results From OrigAMI-1, an Open-Label, Phase Ib/II Study. J Clin Oncol. 2026 Jun 10;44(17):1624-1634. doi: 10.1200/JCO-25-02187. Epub 2026 Apr 21.
- Individual participant dataSharing planned: Yes. The data sharing policy of Johnson \& Johnson Innovative Medicine is available at innovativemedicine.jnj.com/our-innovation/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
53 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Amivantamab IV, Fluorouracil and Leucovorin in people with Advanced or Metastatic Colorectal Cancer, run by Janssen Research & Development, LLC at 53 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 53 sites in United States, Spain, Taiwan, South Korea, Belgium and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Contact (844-434-4210, Participate-In-This-Study1@its.jnj.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cohorts A, B, and C: Objective Response Rate (ORR) (time frame: Up to 4 years 3 months). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05379595, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Nov 2026.