Cetuximab plus capecitabine every three weeks as first-line maintenance therapy for RAS/BRAF wild-type metastatic colorectal cancer: a phase Ib dose-escalation study

Abstract Cetuximab plus fluoropyrimidine every two weeks (Q2W) is a common maintenance approach for RAS/BRAF wild-type metastatic colorectal cancer, but is limited by infusion burden and schedule misalignment. We conducted a phase Ib, nonrandomized 3 + 3 dose-escalation study evaluating cetuximab (400-700 mg/m 2 ) every three weeks (Q3W) synchronized with capecitabine (1000 mg/m 2 twice daily, days 1-14 every 21-day cycle) after first-line induction without disease progression. Six additional patients received standard cetuximab (500 mg/m 2 ) plus infusional 5-fluorouracil/leucovorin every two weeks (Q2W) as a pharmacokinetic reference. Among 24 patients (18 every three weeks [Q3W]; 6 every two weeks [Q2W]), no maximum tolerated dose was reached up to 700 mg/m 2 every three weeks (Q3W), and safety was consistent with known cetuximab and capecitabine-related toxicity. At 700 mg/m 2 Q3W, cetuximab trough concentrations approached those observed with the Q2W reference regimen, and exploratory median progression-free survival was 13.4 months. These findings support cetuximab 700 mg/m 2 Q3W plus capecitabine as the proposed recommended phase II dose (RP2D) regimen for further prospective evaluation. ClinicalTrials.gov: NCT05775900.