None listed
Conditions
Interventions
Drug : The dosage of amivantamab will be based on the participants BW during screening. Participants will receive 1,050 mg if BW is <80 kg or 1,400 mg if BW is =80 kg. Qualified site personnel will ad
subsequent dose [planned dose IVF over 2 hrs]).
• Cycles 2+: Days 1 and 15 of each cycle (planned dose IVF over 2 hrs)
On days when both amivantamab and chemotherapy are administered, amivantamab sho
Sponsors
Yonsei University Health System, Severance Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participants must be =19 years of age. 2. The participant must have been previously diagnosed with histologically or cytologically confirmed unresectable or metastatic adenocarcinoma of the colon or rectum. 3. The participant must have a previously characterized tumor with wild-type KRAS, NRAS, and BRAF without evidence of ERBB2/HER2 amplification by immunohistochemistry (IHC) test. Local guidelines and SoC also require evaluation of dMMR/MSI-H status. 4. The participant must be diagnosed with CRC and should have received anti-EGFR and oxaliplatin-based systemic therapy in the metastatic setting (no more than one prior line of systemic therapy is allowed including neo/adjuvant therapy). According to local regulatory approvals and SoC guidelines, the participant must also be eligible for treatment with FOLFIRI. 5. Participants must have measurable disease according to RECIST v1.1. If only one measurable lesion exists, it may be used for screening biopsy as long as baseline tumor assessment scans are performed =7 days after the biopsy. 6. Participants must have ECOG PS 0 or 1. 7. Life expectancy =12 weeks as judged by the Investigator. 8. Participants must have adequate organ and bone marrow function as follows, without a history of red blood cell transfusion, platelet transfusion, or use of granulocyte colony-stimulating factor (G-CSF) within five days prior to the date of the laboratory test. A. Hemoglobin = 9.0 g/dL B. Absolute neutrophil count =1.5?109/L C. Platelets =100?109/L D. ALT and aspartate aminotransferase (AST) =3?upper limit of normal (ULN). If liver metastases are present, = 5?ULN E. Total bilirubin =1.5?ULN (participants with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits) F. Serum creatinine = 1.5?ULN, or calculated by Cockcroft-Gault formula (Refer to Appendix 9: Cockcroft-Graft Formula for Estimated Creatinine Clearance for formula) or directly measured creatinine clearance = 50 mL/min 9. Known to be homozygous for the UGT1A1*28 or *6 alleles or is compound or double heterozygous for the UGT1A1*28 and *6 alleles per local guidelines. Participants with Gilbert syndrome must be tested for UGT1A1 per local guidelines. 10. While on study treatment and for 6 months after the last dose of study treatment, a participant must (9-1. Contraception and Barrier Guidelines): A. Not breastfeed or be pregnant B. Not donating gametes (ie, eggs or sperm) or freeze for future use for the purposes of assisted reproduction C. Wear an external condom D. If childbearing potential, i. Negative serum or urine pregnancy test within 72 hours before the first study dose in all women of childbearing potential. ii. Practice at least 1 highly effective method of contraception; if oral contraceptives are used, a barrier method of contraception must also be used E. If a participant’s partner is of childbearing potential, i. The partner must practice a highly effective method of contraception unless the participant is vasectomized 11. The participant must sign an ICF (or their legally acceptable representative must sign) indicating that he or she understands the purpose and procedures required for the study and is willing to participate. 12. Participants must be willing and able to adhere to the lifestyle restrictions specified in this protocol.
Exclusion criteria
Exclusion criteria: 1. Participants who have received prior irinotecan-based chemotherapy. 2. Participants with an identified mutation in KRAS, NRAS, BRAF, or ERBB2/HER2 amplification by immunohistochemistry(IHC) test. 3. Has known allergies, hypersensitivity, or intolerance to excipients of any of the following: A. amivantamab B. any component of FOLFIRI 4. Participant has an uncontrolled illness, including but not limited to the following: A. Active bleeding diathesis B. Ongoing or active infection (including infections requiring antimicrobial therapy) Participants must have completed antibiotic/antimicrobial treatment at least one week prior to the initiation of the study treatment. (e.g. Patients receiving tuberculosis treatment due to active tuberculosis at the time of clinical trial enrollment are excluded.) C. Impaired oxygenation requires continuous oxygen supplementation. D. Psychiatric illness/social situation that would limit compliance with study requirements. 5. Participants have known active CNS metastases or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least four weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days before the first dose of study treatment. 6. Participants with positive serology for HIV, HBV and HCV. A. Positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg) Exception: Participants with a prior history of HBV demonstrated by positivehepatitis B core antibody (HBcAb) are eligible if they have at screening 1) a negative HBsAg and 2) an HBV DNA (viral load) below the lower limit of quantification, per local testing. Participants with a positive HBsAg due to recent vaccination are eligible if HBV DNA (viral load) is below the lower limit of quantification, per local testing. B. Positive hepatitis C antibody (anti-HCV [hepatitis C virus]): Exception: Participants with a prior history of HCV who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible. 7. Anticancer treatment within 14 days before the start of trial treatment, e.g., cytoreductive therapy, radiotherapy (except for palliative bone-directed radiotherapy), immune therapy, or cytokine therapy. 8. Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy). 9. Participants with a medical history of myocardial infarction within six months before treatment, symptomatic CHF (New York Heart Association Class II to IV), unstable angina pectoris, clinically significant cardiac arrhythmias, or a recent (< 6 months) cardiovascular event, including myocardial infarction, unstable angina pectoris, and stroke. 10. Gastrointestinal perforation, fistula, or any arterial thromboembolic event within six months, or any significant gastrointestinal bleeding or significant venous thromboembolism within three months prior to treatment (except for stable venous thromboembolism on ongoing appropriate anticoagulation treatment). 11. History of (non-infectious) ILD/pneumonitis, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. 12. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| overall response rate (ORR) | — |
Secondary
| Measure | Time frame |
|---|---|
| progression-free survival, PFS;overall survival, OS;duration of response, DOR;Disease Control Rate, DCR;Clinical Benefit, Rate, CBR;Safety;Tolerability | — |
Countries
Korea, Republic of
Contacts
Public ContactJoong Bae Ahn
Yonsei University Health System, Severance Hospital
Outcome results
None listed