Safety and activity of pembrolizumab in melanoma patients with untreated brain metastases.

9009 Background: Brain metastases (BrMs) develop in 40% of metastatic melanoma (MM) patients (pts). Untreated BrMs exclude from most clinical trials. In prior trials, treatment of MM with pembrolizumab (pembro), an IgG4 antagonist of the immune checkpoint PD-1, produced response rates of > 30%. A phase 2 study (NCT02085070) was initiated to assess safety and activity of pembro in pts with previously untreated or progressing BrMs. Methods: Pts with BrMs from melanoma (reported here) or lung cancer are eligible if at least 1 asymptomatic 5-20mm BrM not requiring immediate local therapy or systemic steroids is present, and at least 1 BrM is amenable to biopsy or resection. Prior PD-1/PD-L1 inhibitors are excluded. Pembro 10mg/kg is administered every 2 weeks (wks). Brain MRI is repeated at 4 wks to assess safety and restaging is done every 8 wks. Primary endpoint is BrM response by modified RECIST (lesions ≥ 5mm are measurable on MRIs with 1mm slices; up to 5 BrMs are used to determine response). Results: Be...