Phase I/II Trial of Durvalumab plus Tremelimumab and Stereotactic Body Radiotherapy for Metastatic Head and Neck Carcinoma.

PURPOSE: This multi-institutional phase I/II study evaluated the safety and efficacy of tremelimumab (T) and durvalumab (D) in combination with stereotactic body radiotherapy (SBRT) in oligometastatic head and neck squamous cell carcinoma (HNSCC) (ClinicalTrials.gov identifier: xxxxxx). METHODS: Patients with oligometastatic HNSCC (2-10 lesions) received D (1500 mg) and T (75 mg) for four monthly cycles, followed by D monotherapy for an additional eight monthly cycles. SBRT was administered to 2-5 lesions during cycle 2. In phase I, the primary endpoint was safety, while in phase II, the primary endpoint was 6-month progression-free survival (PFS). Secondary endpoints included local control, out of SBRT field objective response rate, and overall survival (OS). RESULTS: Thirty-three evaluable patients were recruited (accrual interrupted by COVID-19). Patients had received 1, 2, and 3 prior lines of systemic therapy in 48%, 21%, and 9% of cases, respectively. The median SBRT dose was 45 Gy (range: 18-50) in 3-5 fractions. There were 9 Grade 3-4 AEs related to D and T, occurring in 7 (21%) patients. One patient experienced a Grade 5 AE due to SBRT (radionecrosis following mucosal re-irradiation); no other Grade 3-5 AEs were attributed to SBRT or the SBRT-immunotherapy combination. Median PFS was 12.8 months (95% CI: 7.17-27.2) with a 6-month PFS of 72.7% (95% CI: 59.0-89.6), while median OS was 28.4 months (95% CI: 22.9-38.9). CONCLUSION: Dual-checkpoint inhibition combined with SBRT was well tolerated and led to promising 6-month PFS, meeting both safety and primary endpoints.