Bintrafusp Alfa and Pimasertib for the Treatment of Patients With Brain Metastases

Inclusion Criteria: * Age \>= 18 years old * Life expectancy \> 12 weeks * Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study * At least one measurable untreated brain lesion \>= 0.5 cm and \< 3.0 cm in the longest axis according to modified RECIST 1.1 * Prior stereotactic radiosurgery (SRS) with up to 3 lesions treated with at least a 14 day interval is allowed as long as the previous treatment volume does not overlap with the current targets * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale * Subjects must be free of neurologic signs and symptoms related to metastatic brain lesions and must not have required or received systemic corticosteroid therapy in the 10 days prior to beginning protocol therapy * Prior treatment with immunotherapy and targeted therapy allowed as long as it did not include a combination of MEK inhibitor (i) + anti-PD(L)-1 antibody and is \> 14 days prior to start of protocol therapy. All tumor types will be eligible and included in the dose escalation phase. Dose expansions will include 10 patients each from lung, breast, and melanoma * Patients with melanoma must have received prior PD-1 based therapy and have evidence of progression * Patients with non-small cell lung cancer (NSCLC) must have received prior PD-1 based therapy and have evidence of progression * Patients with triple-negative breast cancer …