A Study of Amivantamab and FOLFIRI Versus Cetuximab/Bevacizumab and FOLFIRI in Participants With KRAS/NRAS and BRAF Wild-type Colorectal Cancer Who Have Previously Received Chemotherapy (OrigAMI-3)

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 3

Conditions: Colorectal Neoplasms

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06750094

61186372COR3002 (Other Identifier)

2024-513853-66-00 (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) and and the length of time until a participant dies (overall survival), when treated with amivantamab and chemotherapy with 5-fluorouracil, leucovorin calcium (folinic acid) or levoleucovorin, and irinotecan hydrochloride (FOLFIRI) versus either cetuximab or bevacizumab and FOLFIRI given to participants with Kirsten rat sarcoma viral oncogene/ neuroblastoma RAS viral oncogene homolog (KRAS/ NRAS) and v-raf murine sarcoma viral oncogene homolog B (BRAF) wild-type recurrent, unresectable or metastatic colorectal cancer who have previously received chemotherapy.

Enrollment: 700 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have histologically or cytologically confirmed adenocarcinoma of the colon or rectum. Participants must have recurrent, unresectable or metastatic disease
• Be diagnosed to have KRAS, NRAS, and BRAF wild-type (WT) tumor as determined by local testing
• Must agree to the submission of fresh or archival tumor tissue post-progression from the most recent therapy, if clinically feasible
• Have measurable disease according to RECIST v1.1
• Have an eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1
• Participant must have received 1 line of systemic therapy (fluoropyrimidine-based and oxaliplatin-based) for metastatic colorectal cancer (mCRC), with documented radiographic disease progression on or after this line of therapy

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: amivantamab, cetuximab or bevacizumab or 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 who has not received immunotherapy treatments
• Participant with known human epidermal growth factor receptor 2 (HER2)- positive/amplified tumor
• Has prior exposure to irinotecan, 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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700 participants in 2 patient groups

Arm A: Amivantamab + FOLFIRI

Experimental group

Description:

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

Treatment:

Drug: Irinotecan

Drug: 5-fluorouracil

Biological: Amivantamab

Drug: Leucovorin calcium/Levoleucovorin

Arm B: Cetuximab or Bevacizumab + FOLFIRI

Active Comparator group

Description:

Participants will receive either cetuximab or bevacizumab along with FOLFIRI as a chemotherapy regimen for 28-days treatment cycles and will continue to receive the treatment until radiographic disease progression or other discontinuation criteria are met.

Treatment:

Drug: Irinotecan

Biological: Bevacizumab

Drug: 5-fluorouracil

Biological: Cetuximab

Drug: Leucovorin calcium/Levoleucovorin