OCTS-06 A PHASE II STUDY OF NIVOLUMAB WITH IPILIMUMAB AND CABOZANTINIB IN PATIENTS WITH UNTREATED RENAL CELL CARCINOMA BRAIN METASTASES

The incidence of brain metastases(mets) at the diagnosis of renal cell carcinoma (RCC) is 1.51%, and around 12% of patients(pts) with advanced RCC (aRCC) had brain mets. Brain mets confer a poor prognosis. Although systemic therapies including tyrosine kinase inhibitors and immune checkpoint inhibitors have been explored in aRCC pts with brain mets, prospective data are lacking. Cabozantinib was FDA approved for pts with aRCC and retrospective studies have suggested activity in patients with intracranial tumors. The phase III COSMIC-313 trial recently evaluated cabozantinib in combination with nivolumab and ipilimumab and demonstrated significantly improved progression-free survival (PFS) in previously untreated pts with aRCC. However, the role of this combination in aRCC pts with brain mets remains undefined. We propose a study to assess the safety and efficacy of cabozantinib in combination with nivolumab/ipilimumab in RCC pts with untreated brain mets.

This is a phase II study to assess the safety and efficacy of the combination of nivolumab with ipilimumab and cabozantinib in pts with untreated brain mets from RCC. Planned accrual is 40 pts. Pts will receive nivolumab (3mg/kg) and ipilimumab (1mg/kg) IV every 3 weeks for 4 doses and cabozantinib 40mg daily. Then pts will be treated with nivolumab 480mg IV Q 4 weeks and cabozantinib 40mg daily. A lead-in group of 6 pts will be closely monitored for dose limiting toxicities (DLT). If stopping criteria (>3 patients develop DLTs) is met, then treatment will be switched to nivolumab plus cabozantinib omitting ipilimumab. The primary objective is intracranial progression free survival (PFS). Secondary objectives include intracranial safety, objective response rate (intracranial + extracranial) by modified RECIST v1.1 and RECIST v1.1, extracranial PFS, overall survival and correlative studies. As of 4/2024, Lead-in group has been completed with acceptable rate of DLT. Clinical trial information: NCT05048212.