Phase I Trial of Cemiplimab, Radiotherapy, Cyclophosphamide, and GM-CSF in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma.

Abstract

LESSONS LEARNED\nCemiplimab in combination with radiation therapy, cyclophosphamide, and granulocyte macrophage colony-stimulating factor (GM-CSF) did not demonstrate efficacy above what can be achieved with other PD-1 inhibitor monotherapies in patients with Refractory and metastatic head and neck squamous cell carcinoma. The safety profile of cemiplimab combination therapy was consistent with previously reported safety profiles of cemiplimab monotherapy. No new safety signal was observed.\n\n\nBACKGROUND\nRefractory and metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) generally does not respond to PD-1 inhibitor monotherapy. Cemiplimab is a human anti-PD-1 monoclonal antibody. An expansion cohort enrolled patients with R/M HNSCC in a phase I study combining cemiplimab plus radiation therapy (RT), cyclophosphamide, and granulocyte macrophage colony-stimulating factor (GM-CSF).\n\n\nMETHODS\nPatients with R/M HNSCC refractory to at least first-line therapy and for whom palliative RT is clinically indicated received cemiplimab plus RT, cyclophosphamide, and GM-CSF. The co-primary objectives were the safety, tolerability, and efficacy of cemiplimab plus RT, cyclophosphamide and GM-CSF in 15 patients (pts) with R/M HNSCC.\n\n\nRESULTS\nFifteen patients were enrolled. Patients discontinued treatment due to progression of disease. The most common treatment-emergent adverse events (TEAEs) of any grade (Gr) were fatigue (40.0%), constipation (26.7%), and asthenia, dyspnea, maculo-papular rash, and pneumonia (each 20%). The only Gr ≥3 TEAE that occurred in\u20092 pts was pneumonia (13.3%). By investigator-assessment, there was 1 partial response (6.7%); disease control rate was 40.0% (95% CI: 16.3-67.7; 5 with stable disease); 7 patients had progressive disease and 2 were not evaluable. Median progression-free survival by investigator-assessment was 1.8 months (95% CI: 1.7-4.7).\n\n\nCONCLUSION\nThe regimen demonstrated tolerability but not efficacy above that which can be achieved with anti-PD-1 inhibitor monotherapy for R/M HNSCC.