Phase II study of nivolumab and ipilimumab for treatment of metastatic/recurrent adenoid cystic carcinoma (ACC) of all anatomic sites of origin and other malignant salivary gland tumors

Objective: Dual checkpoint inhibitor therapy with nivolumab and ipilimumab has been FDA-approved for a number of cancer sites. However, their role in the treatment of ACC and other salivary gland carcinomas is not well established. Methods and analysis: We performed a Simons two-stage prospective single-institution phase II clinical trial of nivolumab with ipilimumab. Two cohorts were analyzed: patients with metastatic/recurrent ACC and patients with other salivary gland cancers. The primary endpoint was median progression-free survival (PFS); secondary endpoints were overall response rate (ORR), overall survival (OS), and toxicity. Results: Patients with ACC (n=19) and other salivary gland carcinomas (total n=5) were enrolled. The patients with ACC had median OS 30.0 months (95% CI 15.3-NR months), median PFS 8.3 months (95% CI 5.5-30.0 months), and disease control rate (DCR) 53% (10/19). The ORR in the ACC group was 5% (CR 0%, n=0; confirmed PR 5%, n=1), with one patient having continued stable disease at the time of trial conclusion. The patients with other salivary gland cancers had median OS 10.4 months (95% CI 6.21-NR months), median PFS 6.21 months (95% CI 2.83-NR months), and DCR 40% (2/5). The ORR in this cohort was 0%. Conclusion: In patients with recurrent or metastatic ACC and other salivary gland neoplasms, combination nivolumab with ipilimumab resulted in moderate disease control. Further studies are warranted to validate our findings. ### Competing Interest Statement YKC reports grants from AbbVie, BMS, Biodesix, Freenome, Predicine, and Roche/Genentech, as well as personal fees from Neogenomics, AstraZeneca, Foundation Medicine, Guardant Health, Merck, Boehringer Ingelheim, Biodesix, ImmuneOncia, Lilly Oncology, Takeda, Lunit, Jazz Pharmaceutical, NeoImmunTech, Tempus, BMS, Regeneron, and Esai outside the submitted work. VF reports stock and other ownership interests at Johnson & Johnson/Janssen, consulting or advisory roles at ARIAD/Takeda, AstraZeneca, Genentech/Roche, Bristol Myers Squibb, and Novocure, research funding from Takeda Science Foundation, and travel, accommodations, and xpenses from ARIAD/Takeda, AstraZeneca, Bristol Myers Squibb, Novocure. DM has received research funding from Amgen, Merck, Oncolytics and Rafael; scientific advisory board for Actuate, Qurient, OncoOne and an advisory/speaker bureau for Amgen, BMS, Eisai, and Exelixis; has received funding paid to their institution from Acepodia, Actuate Therapeutics, ADC Therapeutics, Amgen, AVEO, Bayer, Blueprint Medicines, BMS, BioNTech, Dialectic Therapeutics, Epizyme, Fujifilm, ImmuneSensor, Immune-Onc Therapeutics, Leap Therapeutics, Lycera Corp, Merck, Millennium, MiNA Alpha, NGM Biopharmaceuticals, Novartis, Oncolytics, Orano Med, Puma, Qurient, Rafael, Repare Therapeutics, Triumvira Immunologics, Vigeo Therapeutics, Warewolf Therapeutics. SS and SK are employees of Lunit. MM is an employee of Astellas Pharmaceuticals. RD, LIC, YO, BA, and IH report no conflicts of interest. ### Clinical Trial NCT03146650 ### Funding Statement Funding, nivolumab, and ipilimumab were provided by Bristol Myers Squib. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB of Northwestern University gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data pertinent to our study has been included in this manuscript or uploaded alongside it as supplementary information.