Intracranial Activity of Tepotinib in Patients (pts) With MET exon 14 (METex14) Skipping NSCLC Enrolled in VISION

Purpose/Objective(s) Brain metastases (BMs), reported in 20–40% of pts with METex14 skipping NSCLC, present a high unmet need with a poor prognosis. Preclinical data from tepotinib, a highly selective MET inhibitor, demonstrated intracranial activity in MET-driven lung cancer orthotopic BM models. In VISION Cohort A (N=152), tepotinib had robust and durable clinical activity in pts with METex14 skipping NSCLC, with an objective response rate (ORR) of 45% and a median duration of response (mDOR) of 11.1 months. Here, we report the intracranial activity of tepotinib. Materials/Methods In VISION, pts with METex14 skipping NSCLC received oral tepotinib 500 mg QD (450 mg active moiety). Pts with BM (neurologically stable on symptomatic therapy with stable steroids, and pts with asymptomatic BM) were eligible. Primary endpoint was systemic ORR per RECIST v1.1; a subgroup analysis in pts with BM (determined by RECIST v1.1) was predefined. An ad-hoc retrospective analysis of brain lesions determined by CT/MRI was conducted by an independent review committee using RANO-BM criteria, which accounts for pts’ clinical status and steroid use. Responses were determined in pts with ≥1 evaluable post-baseline tumor assessment. For those with non-measurable lesions per RANO-BM (enhancing and non-enhancing non-target lesions [NTLs]), disease control in the brain was defined as non-complete response (CR)/non-progressive disease (PD). Data cut-off was July 1, 2020. Results Per RECIST v1.1, 23 pts in Cohort A had BM at baseline. Systemic efficacy was consistent with the overall population (ORR 47.8% [95% CI: 26.8, 69.4], mDOR 9.5 months [95% CI: 5.5, not estimable]). 15 pts were evaluable by RANO-BM; 12 received prior radiotherapy for BM (median 6.4 weeks before tepotinib initiation [range 2.6–44]). Systemic best objective responses (BORs) were partial response (PR; n=9), stable disease (SD; n=3), and PD (n=3). Seven pts had measurable CNS disease per RANO-BM (all with prior radiotherapy); intracranial BORs were PR (n=5; including three with complete disappearance of target lesions), SD (n=1) and PD (n=1). Of eight pts with NTL only, seven achieved intracranial disease control and one had PD. Of the seven with disease control, three had a CR of the enhancing NTL. Conclusion Tepotinib demonstrated robust systemic activity in pts with METex14 skipping NSCLC with BM, complemented by intracranial activity in an ad-hoc analysis using RANO-BM. Small pt numbers, a large proportion of pts with prior radiotherapy for BM, and the retrospective nature of the analysis should be considered. A prospective evaluation of intracranial activity data from VISION Cohort C is ongoing. ©2021 American Society of Clinical Oncology, Inc. Reused with permission. Accepted and presented at ASCO 2021. All rights reserved.