CONCEPT (combination of cetuximab plus fruquintinib treatment ± immunotherapy): A multicenter, randomized, open-label phase II trial in first-line pMMR <i>RAS/BRAF</i> wild-type unresectable metastatic colorectal cancer.

Abstract

TPS3680 Background: In pMMR unresectable metastatic colorectal cancer (mCRC), first-line standards combine cytotoxic chemotherapy with targeted agents (anti-EGFR or anti-VEGF). A chemotherapy-sparing strategy may be clinically relevant for selected patients, and biologically supported by potential synergy between EGFR inhibition and VEGFR blockade, with immunotherapy potentially enhanced by vascular normalization and microenvironment modulation. CONCEPT evaluates the safety and antitumor activity of cetuximab-β plus fruquintinib, with or without immune checkpoint blockade, as a first-line option in pMMR RAS/BRAF wild-type unresectable mCRC. Methods: CONCEPT is an open-label, multicenter, randomized phase II trial. Key eligibility: age 18–85, ECOG 0–1, histologically confirmed colorectal adenocarcinoma, pMMR, KRAS/NRAS/BRAF wild-type, unresectable metastatic disease, and ≥1 measurable lesion per RECIST v1.1. Planned N=70; randomization 1:1:1 to: A) cetuximab-β 500 mg/m² IV q2w + fruquintinib 5 mg PO QD (3 weeks on/1 week off); B) regimen A + PD-1 antibody 200 mg IV q4w; C) regimen A + PD-1/CTLA-4 antibody 5 mg/kg IV q4w. The study uses a seamless two-stage selection design: initial cohort (10 patients/arm) to assess early safety/activity, followed by expansion of one or two selected arm(s) (+20 patients per selected arm). Safety assessments are performed each cycle; radiologic tumor assessment is every 2 cycles. Primary endpoints: progression-free survival (PFS) and safety. Secondary endpoints include objective response rate (ORR), disease control rate (DCR) and overall survival (OS). The study is registered with ClinicalTrials.gov (NCI 07257653). Clinical trial information: NCI 07257653 .