Initial results of a phase II study of nivolumab and ipilimumab in metastatic adrenal tumours

Abstract Background Metastatic primary adrenal tumors include those of cortical origin (ACC) and medullary origin (malignant pheochromocytoma/paraganglioma (MP)). Given the rarity of these cancers, standard treatment options are limited, and outcomes are often dismal. In a previous study of single agent pembrolizumab, the proportion of patients with ACC and MP found to have disease control at 6 months defined as stable disease or better using RECIST v1.1 was greater than 25% of patients. Given the FDA approval of nivolumab and ipilimumab (N+I) with both melanoma and metastatic renal cell carcinoma with enhanced overall response rates (ORR) compared to single agent nivolumab in these diseases we sought to study this combination in rare genitourinary tumors (GU). NCT03333616 is a multicenter, single arm, phase II study of N+I in rare GU tumors including cohorts for ACC and MP, urothelial cancer pure variants, and other rare GU tumors. Herein, we report the preliminary results of the fully accrued adrenal cohort. Methods Eligible patients with ACC or MP required measurable disease as defined by RECIST v1.1, an ECOG performance status of 0-2, and may have received any line of prior therapy excluding prior immunotherapy. Hormonal therapy for hormonally active tumors was allowed. Patients underwent a baseline biopsy and received treatment with N 3 mg/kg and I 1 mg/kg intravenously every 3 weeks for 4 cycles with continued maintenance of N 480 mg IV every 4 weeks. The primary endpoint is overall response rate (ORR) by RECIST 1.1. Accrual is complete with 19 patients enrolled into ACC cohort. Results The ORR will be reported with 80% CI with all patients completing at least one scan. Secondary endpoints of immune-related toxicity rates will also be presented. Conclusions These results will inform the role of immunotherapy combinations in the management of advanced ACC. Clinical trial identification NCT03333616. Legal entity responsible for the study The authors. Funding BMS. Disclosure M.T. Campbell: Honoraria (self): Pfizer; Honoraria (self): Genentech; Honoraria (self): Apricity Health LLC; Advisory / Consultancy: EMD Serono, Inc; Advisory / Consultancy: Genentech, Inc. A.Y. Shah: Honoraria (self): Eisai; Honoraria (self): Oncology Information Group; Honoraria (self): Roche Pharmaceuticals; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): BMS; Research grant / Funding (institution): EMD Serono. M.A. Habra: Research grant / Funding (self): Exelixis; Research grant / Funding (self): HRA Pharma. B.A. McGregor: Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Seattle Genetics; Honoraria (self), Advisory / Consultancy: Nektar; Honoraria (self), Advisory / Consultancy: Exiles; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Genentech; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: EMD Serono; Honoraria (self), Advisory / Consultancy: Decibel; Research grant / Funding (institution): BMS. M.A. Bilen: Advisory / Consultancy: Exelixis; Advisory / Consultancy: Nektar; Advisory / Consultancy: GenomicHealth; Advisory / Consultancy: EMD Serono; Advisory / Consultancy: Sanofi; Research grant / Funding (institution): Bayer; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): Genentech/Roche; Research grant / Funding (self): Incyte; Research grant / Funding (self): Nektar; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Tricon Pharmaceuticals; Research grant / Funding (self): Peleton; Research grant / Funding (self): Pfizer. All other authors have declared no conflicts of interest.