(P 013) A PHASE 2 TRIAL OF CETUXIMAB FOR PATIENTS WITH LOCALLY ADVANCED/METASTATIC CHORDOMA

Objective: Chordoma is a rare malignancy of notochord origin that affects the skull base, spine, and sacrum. Aside from surgical resection and use of radiotherapy for local control measures, there are no approved systemic therapies available for chordoma patients with unresectable or metastatic disease. The epidermal growth factor receptor (EGFR) is widely expressed on chordoma including primary disease and notable with recurrent or metastatic sites. Cetuximab is a recombinant, human/mouse chimeric monoclonal antibody of the IgG1 subtype that competitively inhibits EGF and can potentially induce cytotoxicity through an antibody-dependent cell-mediated mechanism (ADCC) utilizing natural killer (NK) cells as effectors. In vivo testing of cetuximab has demonstrated significant tumor growth inhibition as well as instances of tumor regression in multiple patient derived xenograft models of chordoma. Based on EGFR involvement in chordoma and the promising in vivo efficacy data, a phase II study was developed to evaluate the efficacy of cetuximab for treatment of patients with advanced/metastatic chordoma.

Methods: This investigator-initiated trial (NCT05041127) is a single center, single arm, open-label study of cetuximab for patients with locally advanced (unresectable) or metastatic chordoma who are ≥ 18 years of age with adequate organ function and have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. Patients may have had any prior line of therapy except previous exposure to EGFR inhibitors. A minimum of 10 patients and a maximum of 29 patients will be enrolled onto the trial based on Simon’s two-stage design. Cetuximab will be administered as a 500 mg/m2 intravenous infusion every 2 weeks until disease progression or unacceptable toxicity. The primary end point is response rate according to RECIST 1.1. Secondary objectives include an evaluation of response rate by Choi criteria, evaluation of safety and tolerability of cetuximab, evaluation of progression-free survival (median, at 24 weeks, and 52 weeks), and evaluation of overall survival. Exploratory objectives include evaluating EGFR expression by immunohistochemistry from pre-treatment samples, evaluation of the EGFR proteome (via reverse phase protein array), evaluation of the genome, transcriptome, and immune microenvironment at baseline and on treatment with cetuximab. Research related biopsies will be collected at baseline (prior to treatment with cetuximab) and at 8 weeks on treatment. Archival tissue can replace the baseline biopsy. Patient reported outcomes will be assessed with the MDASI general and MDASI-spine questionnaires at baseline and at several time points on study. Adverse events will be graded as per Common Terminology Criteria for Adverse Events version 5.0.

Results: This phase 2 study will evaluate the efficacy and safety of cetuximab in unresectable or metastatic chordoma. The study will only be conducted at the University of Texas MD Anderson Cancer Center. Enrollment is currently ongoing, and a total of 5 patients have been enrolled onto the study since May 2022.

Conclusion: This is a trial in progress. As a result, there are no conclusions that can be drawn at this time. Eligible and interested patients should be referred for trial consideration.