An Open-label, Single-arm, Multicenter Phase II Study to Evaluate the Efficacy of Amivantamab in Combination With FOLFIRI as a Second-line Treatment in Patients With RAS/BRAF Wild-type Advanced Colorectal Cancer Progressing on Prior Anti-EGFR Based Treatment.

Conditions

• RAS/BRAF Wild-type Advanced Colorectal Cancer Patients

Eligibility Criteria

Sex

ALL

Age

19 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Amivantamab + FOLFIRI — DRUG
  The dosage of amivantamab will be based on the participant's body weight during screening. Participants will receive 1,050 mg if BW is \<80 kg or 1,400 mg if BW is ≥80 kg. * Cycle 1: once weekly (with the first dose split over Day -2 \[350 mg, IVF for 4-6hrs\] and Day -1 \[remainder of the dose, IVF for 6-8hrs\]; 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 should be administered before chemotherapy. In general, leucovorin 400 mg/m2 IV over 2 hours and irinotecan 180 mg/m2 IV over 90 min, then 5-FU 400 mg/m2 IV bolus followed by 5-FU continuous infusion 2,400 mg/m2 over approximately 46-48 hours or 1,200 mg/m2/day for two days. Irinotecan and leucovorin may be administered concurrently (via separate infusion lines) or sequentially according to the institutional standard.

Study Details

This trial is a multicenter, single arm study of efficacy of amivantamab in combination with FOLFIRI in RAS/BRAF wild-type advanced colorectal cancer patients progressed prior treatment including oxaliplatin based chemotherapy. This trial will be conducted by Severance Hospital that is responsible for the project management of the trial. Patient recruitment will take at 3 institutions. Participants will be treated for up to 24 cycles (approximately 2 years) after initiation of treatment with intravenous 1050mg(BW\<80kg) or 1400mg(BW≥80kg) of amivantamab every 4 weeks in combination with FOLFIRI. FOLFIRI includes folic acid, 5-FU and irinotecan. FOLFIRI will be administered intravenously with folic acid 400 mg/m², 5-FU 2400 mg/m², and irinotecan 180 mg/m² every 2 weeks. This study will use ORR based on RECIST 1.1 criteria as the primary endpoint and the tumor assessment will be done every 8 weeks. Secondary endpoints are DCR, PFS, OS, and safeties. Exploratory biomarkers in tumor tissue and ctDNA in blood will be investigated in both pre-treatment and post-treatment periods.

Key Dates

Start date

May 31, 2025

Status verified

Feb 2025

Primary completion

May 31, 2027

Completion

Dec 31, 2027

Study Design

Enrollment

85 participants (estimated)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Amivantamab in combination with FOLFIRI
  Amivantamab will be administered as an IV infusion in 28-day cycles in combination with FOLFIRI IV infusion every 2 weeks.

Primary Outcome Measure

Overall Response Rate [ Time Frame: every 8 weeks Up to 2 years 11 months ]