Unresectable or Metastatic Left-sided Colorectal Cancer Cancer
Conditions
Interventions
• Screening Phase (up to 28 days)
• Treatment Phase (until 30 days after stopping the study treatment)- Eligible participants will be randomly (by chance) assigned to either of the 2 groups:
• Arm 1:
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Be at least 18 years of age at the time of informed consent. 2. Have histologically or cytologically confirmed adenocarcinoma of the left-sided colorectal cancer (CRC), as specified within the study protocol. Participants must have unresectable or metastatic disease. 3. 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) tumour, as determined by local testing. 4. Must agree to the submission of fresh tumour tissue. 5. Have measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. If only 1 measurable lesion exists, it may be used for the screening biopsy as long as baseline tumour assessment scans are performed equal to or more than 7 days after the biopsy. 6. Has not received any prior systemic therapy for unresectable or metastatic CRC. Following prior adjuvant/neoadjuvant therapy in the non-metastatic disease is permitted. However, the last course of adjuvant or neoadjuvant chemotherapy must have concluded more than 12 months prior to CRC recurrence/metastases. 7. Have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1. 8. Have at least 1 of the following: a. Serum creatinine less than or equal to 1.5 times upper limit of normal (ULN). b. Estimated glomerular filtration rate (eGFR) based on the Modified Diet in Renal Disease (MDRD) 4-variable formula or directly measured creatinine clearance equal to or more than 50 millilitres per minute. 9. Participants must meet the protocol specified hepatic function requirements. 10. Participants must meet the protocol specified hematologic function requirements. 11. While on study treatment and for 9 months after the last dose of study treatment, a participant must not breastfeed or be pregnant, not donate gametes (i.e., eggs or sperm) or freeze for future use for the purposes of assisted reproduction, and must also wear an external condom. If the participant is of childbearing potential, they must: a. Have a negative highly sensitive (e.g., beta-human chorionic gonadotropin [ß-hCG]) pregnancy test at screening and within 24 hours before randomisation and agree to further pregnancy tests as per the protocol schedule; and b. Practice at least 1 highly effective method of contraception; if oral contraceptives are used, a barrier method of contraception must also be used. If a participant’s partner is of childbearing potential, the partner must practice a highly effective method of contraception unless the participant is vasectomised. 12. Must sign an Informed Consent Form (ICF; or their legally designated representative must sign) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study. 13. Be willing and able to adhere to the lifestyle restrictions specified in this protocol.
Exclusion criteria
Exclusion criteria: 1. Uncontrolled illness, including but not limited to the conditions specified in the protocol. 2. Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis/pulmonary fibrosis, or has current ILD/pneumonitis, or suspected ILD/pneumonitis/pulmonary fibrosis cannot be ruled out by imaging at screening. 3. Has known allergies, hypersensitivity, or intolerance to excipients of amivantamab, cetuximab, any component of mFOLFOX6 (participants receiving mFOLFOX6), or any component of FOLFIRI (participants receiving FOLFIRI). 4. Participant has a history of clinically significant cardiovascular disease, as specified in the study protocol. 5. Has or will have any of the following: a. An invasive operative procedure with entry into a body cavity within 4 weeks or without complete recovery before the first administration of study treatment (see protocol specified exclusions). b. Significant traumatic injury within 3 weeks before the start of the first administration of study treatment (all wounds must be fully healed prior to Day 1). c. Expected major surgery while the investigational agent is being administered or within 6 months after the last dose of study treatment. Note: Port placement for chemotherapy administration is allowed. 6. 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). Prior or concurrent second malignancies must be reviewed and agreed to with the medical monitor. 7. Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status. 8. Participant with known Receptor tyrosine-protein kinase erbB-2 (HER2) -positive/amplified tumour. 9. Has prior exposure to any agents that target epidermal growth factor (EGFR) or mesenchymal epithelial transition (MET) (including but not limited to protein products, monoclonal antibodies, tyrosine kinase inhibitors, or antisense oligonucleotide therapy). 10. Participant with known complete absence of dihydropyrimidine dehydrogenase (DPD) activity. 11. Participant who are to receive FOLFIRI must meet additional protocol specific disease characteristics. 12. Has symptomatic or untreated brain metastasis. 13. Has medical history or known presence of leptomeningeal disease or spinal cord compression. 14. HIV-positive participants are not eligible if they meet any of the specific protocol criteria. 15. Has active hepatitis of infectious origin at screening. 16. Had radiation therapy within 28 days before randomisation. 17. Requires a prohibited medication that cannot be discontinued, substituted, or temporarily interrupted during the study. 18. Received an investigational treatment (including investigational vaccines but not including anticancer therapy) or used an invasive investigational medical device within 8 weeks of randomisation. 19. Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progressions-free survival (PFS) (using RECIST v1.1), as assessed by Blinded Independent Central Review (BICR) from randomisation until the date of objective disease progression or death (due to any cause), whichever comes first | — |
Secondary
| Measure | Time frame |
|---|---|
| Measured using patient records between study treatments: 1. Overall survival (OS). 2. Objective response rate (ORR), as assessed by BICR. 3. PFS and ORR, as assessed by investigator. 4. Duration of response (DoR), as assessed by BICR and investigator. 5. PFS2 (PFS after first subsequent therapy). 6. Disease control rate (DCR), as assessed by BICR and investigator. 7. Time to treatment failure. 8. Curative resection rate. 9. Incidence and severity of adverse events (AEs) and laboratory abnormalities. 10. Change from baseline and time to worsening in symptoms and functioning, as measured by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EORTC QLQ-CR29. 11. Treatment group differences in overall side effect burden, as measured by EORTC item 168. | — |
Countries
Belgium, Brazil, Canada, China, England, France, Germany, Hungary, India, Israel, Italy, Japan, Malaysia, Netherlands, Poland, Scotland, Spain, Sweden, Taiwan, Türkiye, United Kingdom
Outcome results
None listed