Recurrent, unresectable or metastatic 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: Ami
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 colon or rectum. 3. Be diagnosed to have KRAS, NRAS, and BRAF WT tumour as determined by local testing. 4. Agree to the submission of fresh or archival tumour tissue post-progression from the most recent therapy, if clinically feasible. 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. Participant must have received 1 line of systemic therapy for metastatic colorectal cancer (mCRC), with documented radiographic disease progression on or after this line of therapy. 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 equal to or less than 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 6months 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. 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 the protocol
Exclusion criteria
Exclusion criteria: 1. Uncontrolled illness, including but not limited to the conditions specified in the protocol. 2. Has medical history of (non-infectious) interstitial liver 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. 3. Has known allergies, hypersensitivity, or intolerance to excipients to amivantamab, cetuximab, bevacizumab, or FOLFIRI. 4. Participant has a history of clinically significant cardiovascular disease, including but not limited to the conditions specified in the 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. 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. 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). 7. Participant with known mismatch repair deficiency (dMMR)/ high microsatellite instability (MSI-H) status who has not received immunotherapy treatments. 8. Participant with known Receptor tyrosine-protein kinase erbB-2 (HER2) -positive/amplified tumour. 9. Has prior exposure to irinotecan, or any agents that target epidermal growth factor (EGFR) or mesenchymal epithelial transition (MET), or both. 10. Participant with known complete absence of dihydropyrimidine dehydrogenase (DPD) activity. 11. Known to be homozygous (has two identical alleles [versions]) for the genes UGT1A1*28 or *6 alleles or is compound or double heterozygous for the UGT1A1*28 and *6 alleles per local guidelines. 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 protocol specified criteria. 15. Has active hepatitis of infectious origin at screening. 16. Has had prior chemotherapy, targeted cancer therapy, immunotherapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives whichever is longer, before the first administration of study intervention(s). For agents with long half-lives, the maximum required time since last dose is 4 weeks. The maximum required time since last dose is 28 days. 17. Had radiation therapy within 28 days before randomisation. 18. Has toxicities from previous anticancer therapies not resolved to baseline levels or to Grade less than or equal to 1 prior to randomisation (except for alopecia or post-radiation skin changes [any grade], Grade less than or equal to 2 peripheral neuropathy, and Grade less than or equal to 2 hypothyroidism stable on hormone replacement). 19. Requires a prohibited medication that cannot be discontinued, substituted, or temporarily interrupted during the study. 20. Received an investigational treatment (including investigational vaccines but not including anticancer therapy) or used an invasive investigational medical device within 8 weeks of randomisation. 21. Has any condition for which
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Progression-free survival (PFS; using RECIST v1.1), as assessed by Blinded Independent Central Review (BICR) defined as the time from randomisation until the date of objective disease progression or death (due to any cause), whichever comes first, based on BICR using RECIST v1.1 2. Overall survival (OS) defined as time from the date of randomisation to the date of death due to any cause | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Objective response rate (ORR), as assessed by BICR 2. PFS and ORR, as assessed by investigator 3. Duration of response (DoR), as assessed by BICR and investigator 4. PFS2 (PFS after first subsequent therapy) 5. Disease control rate (DCR), as assessed by BICR and investigator 6. Time to treatment failure 7. Curative resection (R0) rate 8. Incidence and severity of adverse events (AEs) and laboratory abnormalities 9. 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 10. Treatment group differences in overall side effect burden, as measured by EORTC item 168 | — |
Countries
Australia, Belgium, Brazil, China, England, France, Germany, Hungary, India, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Poland, Romania, Spain, Sweden, Taiwan, Thailand, United Kingdom
Contacts
Public Contact. Study Team
Outcome results
None listed