Phase 1/2 Trial of Durvalumab Plus Tremelimumab and Stereotactic Body Radiation Therapy for Metastatic Head and Neck...

This multi-institutional phase 1/2 study evaluated the safety and efficacy of tremelimumab (T) and durvalumab (D) in combination with stereotactic body radiation therapy (SBRT) in oligometastatic head and neck squamous cell carcinoma (ClinicalTrials.gov identifier: NCT03283605).

Patients with oligometastatic head and neck squamous cell carcinoma (2-10 lesions) received D (1500 mg) and T (75 mg) for 4 monthly cycles, followed by D monotherapy for an additional 8 monthly cycles. SBRT was administered to 2 to 5 lesions during cycle 2. In phase 1, the primary endpoint was safety, whereas in phase 2, 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.

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 to 5 fractions. There were 9 Grade 3 to 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 reirradiation); no other Grade 3 to 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), whereas median overall survival was 28.4 months (95% CI, 22.9-38.9).

Dual-checkpoint inhibition combined with SBRT was well tolerated and led to promising 6-month PFS, meeting both safety and primary endpoints.