A randomized phase 2 study of nivolumab and nivolumab combined with ipilimumab in patients (pts) with melanoma brain metastases: The Anti-PD1 Brain Collaboration (ABC Study).

TPS9591 Background: Clinical trials have shown that nivolumab and the combination of nivolumab and ipilimumab improve response rates and progression-free survival (PFS) compared with ipilimumab in pts with metastatic melanoma, however pts with active brain metastases were excluded. We sought to determine the antitumour activity and safety of nivolumab and nivolumab combined with ipilimumab in pts with active melanoma brain metastases (NCT02374242). Methods: This open-label, multisite ph 2 study consists of 3 cohorts. Cohorts 1 (n = 30) and 3 (n = 30) include pts with active melanoma brain metastases with no prior local therapy to the brain and are asymptomatic from the brain metastases. Eligible pts are randomised to either cohort 1: nivolumab only (3mg/kg Q2W) or cohort 3: nivolumab (1mg/kg Q3W x 4, then 3mg/kg Q2W) combined with ipilimumab (3mg/kg Q3W x 4). Cohort 2 (n = 16) includes pts with brain metastases who have either 1) failed local therapy with evidence of intracranial progression (new +/- progressed in previously treated lesions), 2) neurological symptoms related to brain metastases or 3) leptomeningeal disease. Pts with prior treatment with anti-PD1/PDL1/PDL2/CTLA4 therapies are excluded. Pts must have ≥ 1 brain metastasis that measure ≥ 5mm and ≤ 40mm as per RECIST 1.1 by MRI + gadolinium. FET-PET is performed at baseline, wk 6 and wk 12. MRI brain and extracranial CT scans are performed at baseline, 6 wkly until wk 24, and 12 wkly thereafter. The primary endpoint is the best intracranial response ≥ wk 12. Secondary endpoints include best extracranial response, best overall response, intracranial PFS, extracranial PFS, overall PFS and overall survival, as well as safety and tolerability. Cohort 2 completed enrolment in May 2015. 18 and 15 pts have been enrolled in cohort 1 and 3 respectively as of Jan 2015. The data, safety and monitoring board reviewed the study in Dec 2015 and recommended the trial continue as planned. Recruitment is expected to be complete by Oct 2016. Thereafter, an additional two cohorts of nivolumab combined with stereotactic radiosurgery ( ≤ 4 brain metastases) or whole brain radiotherapy ( > 5 brain metastases) will be recruited. Clinical trial information: NCT02374242.