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

ABSTRACT 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 × 12 doses followed by 480 mg iv Q4 weeks × 8 doses and ipilimumab 1 mg/kg iv Q6 weeks × 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.