Safety and efficacy

All patients were screened and monitored throughout the study for AE using CTCAE version 5. Patients were assessed by MRI and CT imaging at screening, during the postsurgical visit and, from cycle four on, every third cycle. Cohort A was assessed for bicompartmental progression simultaneously with Response Assessment in Neuro-Oncology for Brain Metastasis (RANO-BM) for unresected or partially resected CNS disease and Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 for non-CNS disease. Cohort B was assessed by (RANO 1.0) alone⁴⁴. ORR, PFS, and OS were calculated from C1D1. All patients received routine laboratory testing, physical examinations, vital signs, and assessment of Eastern Cooperative Oncology Group (ECOG) performance status. At screening a 12-lead ECG was also performed. Urinalysis was performed at screening and D1. Pregnancy tests for women of child-bearing potential were performed at screening and D1 of each odd cycle. MRI scans were performed on 3 T MRI scanners (Philips, GE, or Siemens). Although not dictated by the protocol, each session usually consisted of 3D pre- and post-contrast T1 weighted images, FLAIR (fluid-attenuated inversion recovery), and diffusion weighted images. T1 pre-contrast, FLAIR images were acquired before administration of contrast agent.