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).
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
225
Amivantamab will be administered as intravenous infusion.
Fluorouracil will be administered as intravenous infusion.
Leucovorin will be administered as intravenous infusion.
Oxaliplatin will be administered as intravenous infusion.
Irinotecan will be administered as intravenous infusion.
Amivantamab will be administered.
O Neal Comprehensive Cancer Center at UAB
Birmingham, Alabama, United States
COMPLETEDUniversity of Southern California
Los Angeles, California, United States
COMPLETEDUniversity of California, Los Angeles UCLA
Los Angeles, California, United States
RECRUITINGGeorgetown University Hospital
Washington D.C., District of Columbia, United States
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 4 years 3 months
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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H Lee Moffitt Cancer Center
Tampa, Florida, United States
COMPLETEDUniversity of Maryland School of Medicine
Baltimore, Maryland, United States
COMPLETEDUniversity of Michigan Health System
Ann Arbor, Michigan, United States
RECRUITINGStart Midwest
Grand Rapids, Michigan, United States
COMPLETEDHattiesburg Clinic
Hattiesburg, Mississippi, United States
RECRUITINGNYU Langone Long Island Clinical Research Associates
New York, New York, United States
RECRUITING...and 43 more locations
Time frame: 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.
Time frame: 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.
Time frame: Up to 4 years 3 months