1286P Activity of tepotinib in brain metastases (BM): Preclinical models and clinical data from patients (pts) with MET exon 14 (METex14) skipping NSCLC

Viteri, Santiago; Veillon, Rémi; Felip, Enriqueta; Le, Xiuning; Garassino, M.; Stanton, T.; Morise, Masahiro; Lee, J; Matsumoto, Shingo; Marinis, Filippo de; Wehler, Thomas; Clark, Anderson; Friese-Hamim, Manja; Stroh, Christopher; Bruns, Rolf; Otto, Gordon; Paik, P.

doi:10.1016/j.annonc.2020.08.1600

Cited by 6 publications

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“…Tepotinib is an oral, once daily, highly selective MET tyrosine kinase inhibitor (TKI), with established clinical activity in patients with MET-driven tumors, and is blood-brain barrier-penetrant (25% of tepotinib in plasma is able to cross into the brain) (12)(13)(14). In the first reported efficacy analysis from VISION, comprising 99 patients with ≥9 months' follow-up, tepotinib had an objective response rate (ORR) of 46.5% across lines of therapy according to independent review (IRC) (15).…”

Section: Introductionmentioning

confidence: 99%

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

Sakai

Felip³

et al. 2022

Clinical Cancer Research

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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

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Section: Introductionmentioning

confidence: 99%

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

Sakai

Felip³

et al. 2022

Clinical Cancer Research

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“…Tepotinib has shown some clinical evidence of intracranial activity through a case report published from the VISION trial. 64 , 65 Intracranial response rates have not been reported. 41 , 64 , 65…”

Section: Clinical Data In Met Ex 14 Nsclcmentioning

confidence: 99%

“… 64 , 65 Intracranial response rates have not been reported. 41 , 64 , 65…”

Section: Clinical Data In Met Ex 14 Nsclcmentioning

confidence: 99%

METExon 14 Skipping Mutations in Non–Small-Cell Lung Cancer: An Overview of Biology, Clinical Outcomes, and Testing Considerations

Socinski

Pennell

Davies

2021

JCO Precision Oncology

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“…Cohort A from the phase 2 VISION nonrandomized clinical trial demonstrated robust and durable clinical activity with tepotinib in patients with MET exon 14 ( MET ex14)-skipping NSCLC, 1 , 2 , 3 based on which, tepotinib was approved for use in several countries globally, including by the US Food and Drug Administration (FDA).…”

Section: Introductionmentioning

confidence: 99%

Tepotinib Treatment in Patients With MET Exon 14–Skipping Non–Small Cell Lung Cancer

Paik

Garassino

et al. 2023

JAMA Oncol

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ImportanceMET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 (METex14)-skipping non–small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches.ObjectiveTo assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with METex14-skipping NSCLC in the VISION study.Design, Setting, and ParticipantsThe VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with METex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021. Cohort C (&gt;18 months’ follow-up) was an independent cohort, designed to confirm findings from cohort A (&gt;35 months’ follow-up). Data cutoff was November 20, 2022.InterventionPatients received tepotinib, 500 mg (450 mg active moiety), once daily.Main Outcomes and MeasuresThe primary end point was objective response by independent review committee (RECIST v1.1). Secondary end points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.ResultsCohorts A and C included 313 patients (50.8% female, 33.9% Asian; median [range] age, 72 [41-94] years). The objective response rate (ORR) was 51.4% (95% CI, 45.8%-57.1%) with a median (m)DOR of 18.0 (95% CI, 12.4-46.4) months. In cohort C (n = 161), an ORR of 55.9% (95% CI, 47.9%-63.7%) with an mDOR of 20.8 (95% CI, 12.6-not estimable [NE]) months was reported across treatment lines, comparable to cohort A (n = 152). In treatment-naive patients (cohorts A and C; n = 164), ORR was 57.3% (95% CI, 49.4%-65.0%) and mDOR was 46.4 (95% CI, 13.8-NE) months. In previously treated patients (n = 149), ORR was 45.0% (95% CI, 36.8%-53.3%) and mDOR was 12.6 (95% CI, 9.5-18.5) months. Peripheral edema, the most common treatment-related adverse event, occurred in 210 patients (67.1%) (35 [11.2%] experienced grade ≥3 events).Conclusions and RelevanceThe findings from cohort C in this nonrandomized clinical trial supported the results from original cohort A. Overall, the long-term outcomes of VISION demonstrated robust and durable clinical activity following treatment with tepotinib, particularly in the treatment-naive setting, in the largest known clinical trial of patients with METex14-skipping NSCLC, supporting the global approvals of tepotinib and enabling clinicians to implement this therapeutic approach for such patients.Trial RegistrationClinicalTrials.gov Identifier: NCT02864992"https://clinicaltrials.gov/ct2/show/NCT02864992"

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1286P Activity of tepotinib in brain metastases (BM): Preclinical models and clinical data from patients (pts) with MET exon 14 (METex14) skipping NSCLC

Abstract: Background: BM occur in 20e40% of NSCLC harboring METex14 skipping. We investigated the activity of the MET inhibitor tepotinib in BM in preclinical models and in pts from the VISION study (NCT02864992). abstracts Annals of Oncology Volume 31 -Issue S4 -2020 S831

Cited by 6 publications

References 0 publications

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

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

METExon 14 Skipping Mutations in Non–Small-Cell Lung Cancer: An Overview of Biology, Clinical Outcomes, and Testing Considerations

Tepotinib Treatment in Patients With MET Exon 14–Skipping Non–Small Cell Lung Cancer

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