Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice

Xiuning Le; Hiroshi Sakai; Enriqueta Felip; Remi Veillon; Marina Chiara Garassino; Jo Raskin; Alexis B Cortot; Santiago Viteri; Julien Mazieres; Egbert F Smit; Michael Thomas; Wade T Iams; Byoung Chul Cho; Hye Ryun Kim; James Chih-Hsin Yang; Yuh-Min Chen; Jyoti D Patel; Christine M Bestvina; Keunchil Park; Frank Griesinger; Melissa Johnson; Maya Gottfried; Christian Britschgi; John Heymach; Elif Sikoglu; Karin Berghoff; Karl-Maria Schumacher; Rolf Bruns; Gordon Otto; Paul K Paik

doi:10.1158/1078-0432.CCR-21-2733

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Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice

Authors: Xiuning Le ; Hiroshi Sakai ; Enriqueta Felip ; Remi Veillon ; Marina Chiara Garassino ; Jo Raskin ; Alexis B Cortot ; Santiago Viteri ; Julien Mazieres ; Egbert F Smit ; Michael Thomas ; Wade T Iams ; Byoung Chul Cho ; Hye Ryun Kim ; James Chih-Hsin Yang ; Yuh-Min Chen ; Jyoti D Patel ; Christine M Bestvina ; Keunchil Park ; Frank Griesinger ; Melissa Johnson ; Maya Gottfried ; Christian Britschgi ; John Heymach ; Elif Sikoglu ; Karin Berghoff ; Karl-Maria Schumacher ; Rolf Bruns ; Gordon Otto ; Paul K Paik

Citation: CLINICAL CANCER RESEARCH, Vol.28(6) : 1117-1126, 2022-03

Journal Title: CLINICAL CANCER RESEARCH

ISSN: 1078-0432

Issue Date: 2022-03

MeSH: Aged ; Antineoplastic Agents / adverse effects ; Brain Neoplasms* / drug therapy ; Brain Neoplasms* / genetics ; Carcinoma, Non-Small-Cell Lung* / drug therapy ; Carcinoma, Non-Small-Cell Lung* / genetics ; Carcinoma, Non-Small-Cell Lung* / pathology ; Cohort Studies ; Exons ; Humans ; Lung Neoplasms* / drug therapy ; Lung Neoplasms* / genetics ; Lung Neoplasms* / pathology ; Piperidines* / adverse effects ; Pyridazines* / adverse effects ; Pyrimidines* / adverse effects ; Retrospective Studies

Abstract: Purpose: Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups.

Patients and methods: This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases. An ad hoc retrospective analysis using Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria assessed intracranial activity.

Results: 152 patients were evaluable for efficacy (median age: 73.1). Overall, objective response rate (ORR) was 44.7% [95% confidence interval (CI): 36.7-53.0]. Patients aged <75 (n = 84) and ≥75 (n = 68) had ORRs of 48.8% (95% CI: 37.7-60.0) and 39.7% (95% CI: 28.0-52.3), respectively. Treatment-naïve (n = 69) versus previously treated (n = 83) patients showed consistent efficacy [ORR (95% CI): 44.9% (32.9-57.4) vs. 44.6% (33.7-55.9); median duration of response (95% CI): 10.8 (6.9-not estimable) vs. 11.1 (9.5-18.5) months]. Of 15 patients analyzed by RANO-BM (12 received prior radiotherapy), 13 achieved intracranial disease control; 5 of 7 patients with measurable brain metastases had partial intracranial responses. Of 255 patients evaluable for safety, 64 (25.1%) experienced grade ≥3 treatment-related adverse events (TRAE), leading to discontinuation in 27 patients (10.6%). Rates of adverse events (AE) were broadly consistent irrespective of prior therapies.

Conclusions: Tepotinib showed meaningful activity across subgroups by age, prior therapies, and brain metastases, with a manageable safety profile and few treatment discontinuations. See related commentary by Rosner and Spira, p. 1055.