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).

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

Advanced or Metastatic Colorectal Cancer

Metastatic Colorectal Cancer

Gastrointestinal Cancer

Advanced Solid Tumors

Cancer

Advanced Solid Malignancies

Advanced Solid Tumor

Solid Tumor, Adult

Neoplasms

Adenocarcinoma

Advanced Stage Solid Tumors

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.

Amivantamab

Fluorouracil

Leucovorin

Oxaliplatin

Irinotecan

Amivantamab IV

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

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.

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.

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.

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.

Number of participants with laboratory values abnormalities, which includes serum chemistry, hematology, coagulation, and urinalysis, will be reported.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

Participant who are treatment-naïve for right-sided unresectable or metastatic CRC. Participants will receive Amivantamab along with mFOLFOX6 SoC chemotherapy.

The purpose of this study is to assess the anti-tumor activity of amivantamab as a
      monotherapy (Cohorts A, B, and C), to characterize the safety of amivantamab when added to
      standard-of care (SoC) chemotherapy in participants with metastatic colorectal cancer (mCRC)
      (Ph2 cohorts), and to assess the recommended phase 2 combination dose (RP2CD) of amivantamab
      when added to SoC chemotherapy (Ph1b cohorts).

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.

O'Neal Comprehensive Cancer Center at UAB

University of Southern California

University of California, Los Angeles UCLA

Georgetown University Hospital

H. Lee Moffitt Cancer Center

University of Maryland School of Medicine

University of Michigan Health System

Start Midwest

Hattiesburg Clinic

NYU Langone Long Island Clinical Research Associates

Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center

Stephenson Cancer Center

Vanderbilt - Ingram Cancer Center

MD Anderson Cancer Center

Institut Jules Bordet

Cliniques Universitaires Saint-Luc

UZ Antwerpen

Universitair Ziekenhuis Gasthuisberg

BC Cancer Agency - Vancouver BC

The Ottawa Hospital Cancer Centre

Princess Margaret Cancer Centre University Health Network

The Second Hospital To Dalian Medical University

Sun Yat-sen University - The Sixth Affiliated Hospital Guangdong Gastrointestinal Hospital

The Second Affiliated Hospital of Zhejiang University College of Medicine

Hubei province tumor hospital

Asklepios Klinik Altona

Ludwig-Maximilians-Universitaet Muenchen

Fondazione IRCCS Istituto Nazionale dei Tumori

A.O. Ospedale Niguarda Ca' Granda

Azienda Ospedaliero Universitaria Pisana

Seoul National University Hospital

Severance Hospital, Yonsei University Health System

Asan Medical Center

Samsung Medical Center

The Catholic University of Korea, Seoul St. Mary's Hospital

University Malaya Medical Centre

Hospital Umum Sarawak

Beacon Hospital Sdn. Bhd.

Ad-Vance Medical Research

Pan American Center for Oncology Trials LLC

Hosp. Univ. Vall D Hebron

Hosp. Gral. Univ. Gregorio Maranon

Hosp. Univ. Ramon Y Cajal

Hosp. Univ. Fund. Jimenez Diaz

Hosp. Univ. Hm Sanchinarro

Hosp. Univ. Marques de Valdecilla

Hosp. Clinico Univ. de Valencia

Changhua Christian Hospital

Kaohsiung Chang Gung Memorial Hospital

Chi Mei Medical Center - Liu Ying

National Cheng Kung University Hospital

National Taiwan University Hospital

Linkou Chang Gung Memorial Hospital

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.

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

Trials at a glance

Trials at a glance

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

Outcome measures

Primary outcome measures

Secondary outcome measures