A Study of Amivantamab and mFOLFOX6 or FOLFIRI Versus Cetuximab and mFOLFOX6 or FOLFIRI as First-line Treatment in Participants With KRAS/NRAS and BRAF Wild-type Unresectable or Metastatic Left-sided Colorectal Cancer

Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)

Timeframe: Up to 4 years and 2 months

PFS is defined as the time from randomization until the date of objective disease progression or death (due to any cause), whichever comes first, as assessed by BICR using response evaluation criteria in solid tumors (RECIST) version (v) 1.1. Participants who have not progressed or have not died at the time of analysis will be censored at their last evaluable RECIST v1.1 assessment date.

Overall Survival (OS)

Timeframe: Up to 7 Years 3 Months

OS is defined as the time from the date of randomization to the date of participant's death due to any cause. Any participant not known to have died at the time of analysis will be censored based on the last recorded date on which the participant was known to be alive.

Objective Response Rate (ORR) as Assessed by BICR

Timeframe: Up to 7 Years 3 Months

ORR is defined as the proportion of randomized participants achieving a best overall response (BOR) of partial response (PR) or complete response (CR), as determined by BICR using RECIST v1.1 criteria. BOR is defined as best response recorded between the date of randomization and the date of first objectively documented progression per RECIST v1.1 or the date of subsequent systemic anti cancer therapy or date of curative-intent procedure, whichever occurs first.

Objective Response Rate (ORR) as Assessed by Investigator

Timeframe: Up to 7 Years 3 Months

ORR is defined as the percentage of randomized participants achieving complete CR or PR, as assessed by the investigator.

Progression Free Survival (PFS) as Assessed by Investigator

Timeframe: Up to 7 Years 3 Months

PFS is defined as the time from randomization until the date of objective disease progression or death (due to any cause), whichever comes first, as assessed by the investigator. Participants who have not progressed or have not died at the time of analysis will be censored at their last evaluable disease assessment date.

Duration of Response (DOR) as Assessed by BICR

Timeframe: Up to 7 Years 3 Months

DOR is defined as time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR, as assessed by BICR using RECIST v1.1 criteria.

Duration of Response (DOR) as Assessed Investigator

Timeframe: Up to 7 Years 3 Months

DOR is defined as time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR, as assessed by the investigator.

Time to Response (TTR) as Assessed by BICR

Timeframe: Up to 7 Years 3 Months

TTR is defined as the time from the date of randomization to the date of first documentation of a response (PR or CR) prior to any disease progression or subsequent systemic anti-cancer therapy or curative-intent procedure, for participants who have PR or CR as BOR, as assessed by BICR.

Time to Response as Assessed by Investigator

Timeframe: Up to 7 Years 3 Months

TTR is defined as the time from the date of randomization to the date of first documentation of a response (PR or CR) prior to any disease progression or subsequent systemic anti-cancer therapy or curative-intent procedure, for participants who have PR or CR as BOR, as assessed by investigator.

Progression-free Survival After Subsequent Therapy (PFS2)

Timeframe: Up to 7 Years 3 Months

PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first.

Disease Control Rate (DCR) as Assessed by BICR

Timeframe: Up to 7 Years 3 Months

DCR is defined as the percentage of randomized participants achieving CR, PR, or stable disease (with minimum duration of 7 weeks) as assessed by BICR using RECIST v1.1 criteria.

Disease Control Rate (DCR) as Assessed by Investigator

Timeframe: Up to 7 Years 3 Months

DCR is defined as the percentage of randomized participants achieving CR, PR, or stable disease (with minimum duration of 7 weeks) as assessed by the investigator.

Time to Treatment Failure

Timeframe: Up to 7 Years 3 Months

Time to treatment failure is defined as time from randomization to discontinuation of therapy for any reason including death, progression, toxicity, or initiation of new anticancer therapy.

Curative Resection (R0) Rate

Timeframe: Up to 7 Years 3 Months

Curative resection (R0) rate is defined as the proportion of participants from the analysis set who underwent curative-intent surgery, where the residual tumor classification was R0.

Number of Participants with Adverse Events (AEs) by Severity

Timeframe: Up to 7 Years 3 Months

An AE can be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. AE severity will be graded according to the national cancer institute common terminology criteria for adverse events (NCI-CTCAE) v5.0. by using the standard grades as follows: Grade 1: Mild; asymptomatic or mild symptoms; Grade 2: Moderate; minimal, local or noninvasive intervention indicated; Grade 3: Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; and Grade 5: Death related to AE.

Number of Participants with Abnormalities in Laboratory Values

Timeframe: Up to 7 Years 3 Months

Participants with abnormalities in laboratory values (such as serum chemistry, hematology) will be reported.

Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Score

Timeframe: From Baseline up to 7 Years 3 Months

The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the health-related quality of life (HRQoL) of participants with cancer. EORTC QLQ-C30 includes 5 functional scales, 3 symptom scales, a global health status / quality of life scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, and more severe symptoms.

Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-C30

Timeframe: Up to 7 Years 3 Months

The EORTC QLQ-C30, is a self-administered, 30-item questionnaire measuring the HRQoL of participants with cancer. EORTC QLQ-C30 includes 5 functional scales, 3 symptom scales, a global health status / quality of life scale, and 6 single items. Responses to items 1-28 are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much." Two global health status items are rated on a 7-point numeric rating scale from 1 "Very Poor" to 7 "Excellent." Higher scores indicate greater functioning, better global health status, and more severe symptom.

Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Colorectal Cancer Module 29 (EORTC-QLQ-C29) Score

Timeframe: From Baseline up to 7 Years 3 Months

The EORTC QLQ-CR29, is a self-administered, 29-item questionnaire measuring the HRQoL of participants with colorectal cancer. The QLQ CR29 includes items that evaluate symptoms (gastrointestinal, urinary, pain, and others) and functional areas (sexual, body image, weight, and anxiety) that are associated with colorectal cancer and its treatments. Responses are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much". All scores are linearly converted into a scale from 0 to 100. Higher scores indicate greater functioning and more severe symptoms.

Time to Worsening in Symptoms and Functioning as Measured by EORTC QLQ-CR29

Timeframe: Up to 7 Years 3 Months

The EORTC QLQ-CR29, is a self-administered, 29-item questionnaire measuring the HRQoL of participants with colorectal cancer. The QLQ CR29 includes items that evaluate symptoms (gastrointestinal, urinary, pain, and others) and functional areas (sexual, body image, weight, and anxiety) that are associated with colorectal cancer and its treatments. Responses are rated on a 4-point Likert response scale ranging from 1 "Not at all" to 4 "Very much". All scores are linearly converted into a scale from 0 to 100. Higher scores indicate greater functioning and more severe symptoms.

Overall Side Effect Burden as Measured by European Organisation for Research and Treatment of Cancer (EORTC) Item 168 Scale Score

Timeframe: Up to 7 Years 3 Months

The EORTC item 168 is a single item used to measure the overall impact of treatment side effects. Responses are rated on a 4-point Likert response scale ranging from 1 "not at all" to 4 "very much." Higher scores indicate severe side effects.