Cetuximab (anti-EGFR mAb) delivers 8% RECIST PRs but high SD/ATR rate in advanced chordoma

Cetuximab is a chimeric monoclonal antibody that blocks EGFR signaling; in this investigator-initiated, single-center Phase 2 trial (NCT05041127), adults with unresectable locally recurrent/metastatic chordoma (mITT n=25; any prior systemic therapy allowed except EGFR inhibitors; median 1 prior line) received cetuximab 500mg/m² IV q2w. At 28.7 months median follow-up, ORR was 8% (2/25 PR), while 92% had stable disease and 48% had any tumor reduction; preliminary median PFS was 9.9 months (95% CI 6.3–13.4) and median OS 38.8 months (95% CI 18.6–NR), with longer PFS in SD-with-any-tumor-reduction vs SD-without reduction (14.2 vs 9.6 months; log-rank p=0.038). Grade 3 cetuximab-related AEs occurred in 27% (most commonly rash, 15%); 15% discontinued due to toxicity—broadly in-family with other chordoma systemic options where RECIST responses are uncommon and median PFS is often ~8–10 months (e.g., imatinib ~9 months; regorafenib ~8 months; sorafenib shows low RECIST PR rates but can stabilize disease).