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 (OrigAMI-2)

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 3

Conditions: Colorectal Neoplasms

Treatments: Biological: Cetuximab; Biological: Amivantamab; Drug: Oxaliplatin; Drug: Leucovorin calcium/Levoleucovorin; Drug: Irinotecan Hydrochloride; Drug: 5-fluorouracil

Study type: Interventional

Funder types: Industry

Identifiers

NCT06662786

61186372COR3001

2024-513852-13-00 (Registry Identifier)

Details and patient eligibility

About

The purpose of this study is to compare how long the participants are disease-free (progression-free survival) when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, oxaliplatin (mFOLFOX6) or 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus cetuximab and mFOLFOX6 or FOLFIRI in adult participants with Kirsten rat sarcoma viral oncogene homolog (KRAS)/ Neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) wild type (WT) unresectable or metastatic left-sided colorectal cancer.

Enrollment: 1,000 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer. Participants must have unresectable or metastatic disease
• Be diagnosed to have Kirsten rat sarcoma viral oncogene (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS), and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type (WT) tumor as determined by local testing
• Must agree to the submission of fresh tumor tissue
• Have measurable disease according to RECIST v1.1
• Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1

Exclusion criteria

• Has medical history of (noninfectious) interstitial lung disease (ILD) /pneumonitis/pulmonary fibrosis or has current ILD/pneumonitis/pulmonary fibrosis, or where suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening
• Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: (a) amivantamab or cetuximab, (b) any component of mFOLFOX6 and, (c) any component of FOLFIRI
• Has a prior or concurrent second malignancy other than the disease under study or one whose natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s)
• Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status and human epidermal growth factor receptor 2 (HER2)-positive/amplified tumor
• Has prior exposure to any agents that target epidermal growth factor receptor (EGFR) or mesenchymal epithelial transition (MET)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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1,000 participants in 2 patient groups

Arm A: Amivantamab in Combination With Chemotherapy

Experimental group

Description:

Participants will receive amivantamab in combination with chemotherapy (mFOLFOX6 \[chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and oxaliplatin\] or FOLFIRI \[chemotherapy consisting of 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride\]) for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.

Treatment:

Drug: 5-fluorouracil

Drug: Irinotecan Hydrochloride

Drug: Leucovorin calcium/Levoleucovorin

Drug: Oxaliplatin

Biological: Amivantamab

Arm B: Cetuximab in Combination With Chemotherapy

Active Comparator group

Description:

Participants will receive cetuximab in combination with chemotherapy (mFOLFOX6 or FOLFIRI) for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.

Treatment:

Drug: 5-fluorouracil

Drug: Irinotecan Hydrochloride

Drug: Leucovorin calcium/Levoleucovorin

Drug: Oxaliplatin

Biological: Cetuximab