Multicenter phase 1-2 trial of durvalumab plus tremelimumab and SBRT for oligometastatic head and neck squamous cell carcinoma

A multicenter phase 1-2 trial in Canada evaluated safety and efficacy of tremelimumab (T) and durvalumab (D) in combination with stereotactic body radiotherapy (SBRT) in oligometastatic (2-10 lesions) head and neck squamous cell carcinoma (HNSCC). Patients 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 (median dose 45 Gy; range18-50; in 3-5 fractions. In phase 1, the primary endpoint was safety, while in phase 2 the primary endpoint was 6-months progression-free survival (PFS) rate. The study recruite 33 evaluable patients, who had received 1, 2, and 3 prior lines of systemic therapy in 48%, 21%, and 9% of cases, respectively. Grade 3-4 adverse events (AEs) related to D and T occurred in 7 patients (21%). 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 rate of 72.7% (59.0-89.6), while median overall survival was 28.4 months (22.9-38.9). The authors conclude that dual checkpoint inhibition combined with SBRT was well tolerated and led to promising 6-month PFS rate.