Dual PD-1 and CTLA4 Immune Checkpoint Blockade and Hypofractionated Radiation in Patients With Advanced Salivary Gland Cancers.

BACKGROUND: No standard systemic therapy exists for recurrent/metastatic salivary gland cancer (R/M SGC). We explored the safety and activity of nivolumab and ipilimumab with palliative hypofractionated radiation (XRT) in this population. METHODS: This Phase I/II Trial enrolled R/M SGCs with evidence of progression, ECOG 0-1, no prior anti-PD-1 or CTLA4 therapy, measurable disease excluding the XRT site. Nivolumab 3 mg/kg iv Q2 weeks x 12 doses followed by 480 mg iv Q4 weeks x 8 doses and ipilimumab 1 mg/kg iv Q6 weeks x 4 doses was given. Twenty four gray XRT was given over three fractions, 2 weeks after the first dose of nivolumab. The primary endpoint was safety; secondary endpoints included RECIST 1.1 response (non-radiated lesions), progression free, and overall survival. RESULTS: Between April 2019 and May 2022, 20 pts. were enrolled, the median age was 58 (range 27-77 years), 10 (50%) were male, and 12 (60%) had ECOG 0. Five (20%) Grade 3 AEs were observed in three pts.; no Grade 4 or 5 toxicities were observed. Among 19 response-evaluable patients, RECIST 1.1 PRs were observed in 4 (21%), in 2 pts. with salivary duct, 1 acinic cell, and 1 adenoid cystic, SD in 6 (31.5%) and PD in 9 (47.5%). With a median follow-up of 16 months, median OS was 25 months (95% CI: [18.7, 31]) and median PFS was 7.3 months (95% CI [2.5, 18.7]). CONCLUSION: Nivolumab/ipilimumab and palliative XRT result in low rates of severe toxicities and modest response rates for SGC; further work is necessary to explore predictors for response.