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Patients with recurrent head and neck squamous cell carcinoma (HNSCC) after previous platinum-based chemotherapy have a median survival of 6 months or less. MC ROR1771, a multisite prospective  study to evaluate the addition of stereotactic body proton therapy (SBPT) to nivolumab in a platinum-refractory population, demonstrated median overall survival of 12.5 months from initiation of nivolumab, with progression free survival of 4.5 months. This favorably compared with CheckMate 141, where nivolumab led to a median 7.5-month survival. The planned biochemical analysis of T-cell subpopulation and biomarker response within MC ROR1771 is herein presented.

Patients with metastatic histologically confirmed HNSCC from any primary site were eligible. Two cycles of nivolumab every other week were followed by SBPT to 1-2 target lesion(s). Maintenance nivolumab continued every other week with follow-up for progression and treatment toxicity. Subsequent oligoprogression was treated with stereotactic body radiotherapy or SBPT as indicated. Objective criteria included target lesion response rate, overall survival, progression-free survival, time to distant metastasis, toxicity, and evaluation of potential predictive biomarkers, with evaluation of change from baseline.

15 patients enrolled, 13 receiving SBPT, and one withdrew; of the remaining 12, 3 had laryngeal primary, 1 nasopharyngeal, and 8 oropharyngeal. 4 patients received one cycle of chemotherapy before enrollment, 3 patients two cycles, and 5 patients three cycles. 10 received concurrent chemoradiation in first line (5 definitive, 5 adjuvant), with 1 receiving neoadjuvant chemotherapy prior to chemoradiation, and one presenting with metastatic disease. SBPT dosing ranged from 35-50 Gy. Combination therapy generated response within T-cell populations, with some response to nivolumab noted followed by notable change following SBPT between days 15 and 30. Within the population, Bim+/CD8+CD11aHi was unchanged. Most patients experienced an initial decrease in  %PD-1+/CD8+CD11aHi and TCM, CD8+CCR7+CD45RA- cells with nivolumab administration followed by a subsequent increase following SBPT; the inverse was noted for TEM, CD8+CCR7-CD45RA- and TEF, CD8+CCR7-CD45RA+ cells. MC ROR 1771 demonstrated overall and progression free survival favorably comparable to CheckMate 141; biomarker analysis has demonstrated significant shifts in T-cell populations with systemic response noted both to initiation of nivolumab as well as following SBPT. Further evaluation is ongoing, and prospective evaluation of SBPT and immunotherapy are warranted.

MC ROR 1771 demonstrated overall and progression free survival favorably comparable to CheckMate 141; biomarker analysis has demonstrated significant shifts in T-cell populations with systemic response noted both to initiation of nivolumab as well as following SBPT. Further evaluation is ongoing, and prospective evaluation of SBPT and immunotherapy are warranted.