Prospective, open-label, multicenter phase II (two-stage) trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) for advanced MpBC. ORR was 18%; 3/17 patients achieved objective responses (1 complete, 2 partial responses) (2 spindle cell, 1 chondromyxoid histology), which are ongoing at 28+, 33+ and 34+ months, respectively. Median PFS and OS were 2 and 12 months, respectively. Responses occurred in tumors with low tumor mutational burden, low PD-L1 and absent TILs. The ipilimumab and nivolumab combination showed no new safety signals and met its primary endpoint with 18% ORR in advanced, chemotherapy-refractory MpBC. All responses are ongoing at >2 to almost 3 years later. The effect of ipilimumab and nivolumab was associated with exceptional responses in a subset of patients versus no activity.

The tumor was mismatch repair-proficient, harbored no actionable variants, and the tumor mutation burden was low at 6.8 Mut/Mb. Tumor PD-L1 expression by immunohistochemistry was <1%....our patient elected to receive self-funded dual immunotherapy with ipilimumab 3 mg/kg IV and nivolumab 1 mg/kg IV thrice weekly....maintenance nivolumab 3 mg/kg IV twice weekly was continued for 17 cycles over 8 months. There was a marked clinical and radiological response of the primary pituitary carcinoma and all metastatic lesions that was sustained for eight months...