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  • 1
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    Long-term outcomes of tepotinib in patients with MET exon 14 skipping NSCLC from the VISION study.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 9060-9060
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 9060-9060
    Abstract: 9060 Background: Tepotinib is a highly selective MET inhibitor with clinical activity in patients (pts) with MET exon 14 ( METex14) skipping NSCLC. We previously reported robust and durable activity of tepotinib from the Phase II VISION study (NCT02864992; data cut: Feb 20, 2022; median follow-up: 26.1 months [mos]; Thomas, et al. WCLC 2022). Here, we report long-term outcomes from VISION, fulfilling an FDA post-market requirement (data cut: Nov 20, 2022; follow-up: Cohort A [primary cohort] ≥35 mos, Cohort C [confirmatory cohort] ≥18 mos). Methods: Pts with advanced METex14 skipping NSCLC detected by liquid and/or tissue (T+) biopsy received tepotinib 500 mg (450 mg active moiety) once daily. The primary endpoint was objective response by independent review using RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: Of 313 pts enrolled, median age was 72 years (range 41–94) and pts received tepotinib for a mean (standard deviation [SD] ) of 11.5 mos (11.6); median follow-up was 32.6 mos (range 0.3–71.9). First line (1L) pts (n=164; median age: 74 years [range 47–94]; male: 50.6%; ECOG PS 1: 72.0%; smoking history: 53.7%) received tepotinib for a mean (SD) of 12.4 mos (12.2), with 27 pts still receiving treatment. ORR was 57.3% (95% CI: 49.4, 65.0), mDOR was 46.4 mos (13.8, not estimable [ne] ), mPFS was 12.6 mos (9.7, 17.7), and mOS was 21.3 mos (14.2, 25.9). Among 111 1L T+ pts, ORR was 58.6% (48.8, 67.8), mDOR was 46.4 mos (15.2, ne), mPFS was 15.9 mos (11.0, 49.7), and mOS was 29.7 mos (18.8, ne) (Table). Second-or-later line (2L+) pts (n=149; median age: 71 years [range 41–89]; male: 47.7%; ECOG PS 1: 75.8%; smoking history: 40.9%) received tepotinib for a mean (SD) of 10.5 mos (11.0), with 10 pts still receiving treatment. ORR was 45.0% (36.8, 53.3) and mDOR was 12.6 mos (9.5, 18.5). Across all 313 pts, ORR was 51.4% (45.8, 57.1), mDOR was 18.0 mos (12.4, 46.4), mPFS was 11.2 mos (9.5, 13.8), and mOS was 19.6 mos (16.2, 22.9). No new safety concerns were observed. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 34.8% of pts; 14.7% of pts discontinued treatment due to TRAEs. Any grade related peripheral edema occurred in 67.1% of pts (Grade ≥3: 11.2%). Conclusions: The long-term outcomes of VISION demonstrate the robust and durable clinical activity of tepotinib, particularly in 1L T+ pts, and manageable safety profile, further defining its use in clinical practice. Clinical trial information: NCT02864992 . [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.9060
    RVK:
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    RVK:
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
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  • 2
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    Phase II study of tepotinib in NSCLC patients with MET ex14 mutations.
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 15_suppl ( 2019-05-20), p. 9005-9005
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 9005-9005
    Abstract: 9005 Background: MET exon 14 skipping ( METex14) mutations - reported in 3~4% of NSCLC patients (pts) - are activating, sensitive to MET inhibition and can be conveniently detected using liquid biopsy (LBx). We report data from an ongoing single-arm phase II study of tepotinib, a highly selective MET inhibitor, in NSCLC pts with METex14 mutations identified by LBx or tumor biopsy (TBx) (NCT02864992). Methods: Pts with advanced WT EGFR/ALK NSCLC, prospectively enrolled via either LBx (≥60 pts) or TBx (≥60 pts, overlap anticipated) central RNA-based METex14 mutation testing, receive tepotinib 500 mg QD until progression, intolerable toxicity or withdrawal. Primary endpoint: objective response rate (ORR) by independent review (IRC). Secondary endpoints: ORR by investigator assessment (INV) and safety. Results: To date, 85 pts have been enrolled (55 LBx pts and 52 TBx pts). At data cut-off (16 Oct 2018), in 35 evaluable LBx pts (≥2 post-baseline assessments or discontinuation for any reason), ORR was 51.4% by IRC and 63.9% by INV. In 41 evaluable TBx pts, ORR was 41.5% by IRC and 58.5% by INV. Median duration of response (mDoR) and ORR by line of treatment are shown in the table. Any grade treatment-related adverse events (TRAEs) reported by ≥10% of 69 pts evaluable for safety were peripheral edema (47.8%), diarrhea (18.8%), nausea (15.9%), asthenia (10.1%). No TRAEs were grade 4 or led to death. TRAEs led to permanent discontinuation in 2 (2.9%) pts (1 ILD, 1 diarrhea & nausea). Conclusions: Tepotinib has promising activity with a long DoR across treatment lines in NSCLC pts with METex14 mutations detected by LBx or TBx. The safety profile was favorable. Recruitment is ongoing. Clinical trial information: NCT02864992. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.15_suppl.9005
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
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  • 3
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    Abstract A097: Phase II trial of the c-Met inhibitor tepotinib in patients with advanced non-small cell lung cancer harboring MET exon 14-skipping mutations
    American Association for Cancer Research (AACR) ; 2018
    In:  Molecular Cancer Therapeutics Vol. 17, No. 1_Supplement ( 2018-01-01), p. A097-A097
    Details
    In: Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 17, No. 1_Supplement ( 2018-01-01), p. A097-A097
    Abstract: Background: Approximately 3-4% of non-small cell lung cancers (NSCLCs) harbor activating mutations of the MET proto-oncogene that cause exon 14 skipping (METex14) and accumulation of c-Met lacking a juxtamembrane domain. Such tumors are sensitive to nonselective kinase inhibitors with activity against c-Met, so selective c-Met inhibitors may have greater efficacy and/or tolerability. This single-arm phase II trial (NCT02864992) is investigating the efficacy and safety of the potent and selective c-Met inhibitor tepotinib in patients (pts) with NSCLC harboring METex14. Methods: Eligible patients (pts) are adults with stage IIIB/IV NSCLC and METex14 mutations identified in tumor and/or circulating tumor DNA (ctDNA) in plasma (liquid biopsy) by a central laboratory. Pts with EGFR-activating mutations, ALK rearrangements, or & gt;2 lines of prior therapy are excluded. Pts receive tepotinib 500 mg QD on a 21-day cycle until disease progression, intolerable toxicity, or withdrawal from treatment for other reasons. Primary endpoint: objective response rate (ORR). Secondary endpoints: progression-free and overall survival, safety, pharmacokinetics, and quality of life. Recruitment of up to 120 (minimum 60 tumor, 60 ctDNA METex14-positive) pts in Europe, USA, and Japan is planned. Results: Five pts (age 55-77 years; 4 stage IV, 1 stage IIIB; all male; 4 Caucasian, 1 Asian) have been enrolled. Pts have currently completed 0-8 cycles of tepotinib therapy. Most adverse events observed to date have been grade 1/2 in severity, mostly unrelated to tepotinib treatment. One grade ≥3 tepotinib-related AE has occurred: grade 3 increased serum amylase. One pt has died due to his disease. Of the four pts with post-baseline tumor evaluations, two have confirmed partial response, one unconfirmed partial response, and one (with only one post-baseline assessment) stable disease. Conclusions: Initial data suggest that tepotinib 500 mg QD has promising activity in METex14 NSCLC. The safety profile of tepotinib appears favorable. Recruitment to the trial is ongoing. Citation Format: Enriqueta Felip, Remi Veillon, Santiago Viteri, Jürgen Scheele, Rolf Bruns, Paul K. Paik. Phase II trial of the c-Met inhibitor tepotinib in patients with advanced non-small cell lung cancer harboring MET exon 14-skipping mutations [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A097.
    Type of Medium: Online Resource
    ISSN: 1535-7163 , 1538-8514
    URL: Article
    DOI: 10.1158/1535-7163.TARG-17-A097
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 4
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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
    American Association for Cancer Research (AACR) ; 2022
    In:  Clinical Cancer Research Vol. 28, No. 6 ( 2022-03-15), p. 1117-1126
    Details
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 28, No. 6 ( 2022-03-15), p. 1117-1126
    Abstract: 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 & lt;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
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    URL: Article
    DOI: 10.1158/1078-0432.CCR-21-2733
    RVK:
    XA 36791
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 5
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    Tepotinib Treatment in Patients With MET Exon 14–Skipping Non–Small Cell Lung Cancer : Long-term Follow-up of the VISION Phase 2 Nonrandomized Clinical Trial
    American Medical Association (AMA) ; 2023
    In:  JAMA Oncology Vol. 9, No. 9 ( 2023-09-01), p. 1260-
    Details
    In: JAMA Oncology, American Medical Association (AMA), Vol. 9, No. 9 ( 2023-09-01), p. 1260-
    Abstract: MET inhibitors have recently demonstrated clinical activity in patients with MET exon 14 ( MET ex14)-skipping non–small cell lung cancer (NSCLC); however, data with longer follow-up and in larger populations are needed to further optimize therapeutic approaches. Objective To assess the long-term efficacy and safety of tepotinib, a potent and highly selective MET inhibitor, in patients with MET ex14-skipping NSCLC in the VISION study. Design, Setting, and Participants The VISION phase 2 nonrandomized clinical trial was a multicohort, open-label, multicenter study that enrolled patients with MET ex14-skipping advanced/metastatic NSCLC (cohorts A and C) from September 2016 to May 2021. Cohort C ( & amp;gt;18 months’ follow-up) was an independent cohort, designed to confirm findings from cohort A ( & amp;gt;35 months’ follow-up). Data cutoff was November 20, 2022. Intervention Patients received tepotinib, 500 mg (450 mg active moiety), once daily. Main Outcomes and Measures The 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. Results Cohorts 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 Relevance The 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 MET ex14-skipping NSCLC, supporting the global approvals of tepotinib and enabling clinicians to implement this therapeutic approach for such patients. Trial Registration ClinicalTrials.gov Identifier: NCT02864992
    Type of Medium: Online Resource
    ISSN: 2374-2437
    URL: Article
    DOI: 10.1001/jamaoncol.2023.1962
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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  • 6
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    O13-3 Tepotinib in patients with MET exon 14 (METex14) skipping advanced NSCLC: Updated efficacy results from VISION cohort A
    Elsevier BV ; 2021
    In:  Annals of Oncology Vol. 32 ( 2021-07), p. S290-
    Details
    In: Annals of Oncology, Elsevier BV, Vol. 32 ( 2021-07), p. S290-
    Type of Medium: Online Resource
    ISSN: 0923-7534
    URL: Article
    DOI: 10.1016/j.annonc.2021.05.540
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 7
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    Tepotinib in Non–Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations
    Massachusetts Medical Society ; 2020
    In:  New England Journal of Medicine Vol. 383, No. 10 ( 2020-09-03), p. 931-943
    Details
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 383, No. 10 ( 2020-09-03), p. 931-943
    Type of Medium: Online Resource
    ISSN: 0028-4793 , 1533-4406
    URL: Article
    DOI: 10.1056/NEJMoa2004407
    RVK:
    XA 10000
    Language: English
    Publisher: Massachusetts Medical Society
    Publication Date: 2020
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  • 8
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    Primary efficacy and biomarker analyses from the VISION study of tepotinib in patients (pts) with non-small cell lung cancer (NSCLC) with MET ex14 skipping.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. 9556-9556
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 9556-9556
    Abstract: 9556 Background: Preliminary tepotinib data showed durable activity in pts with NSCLC with METex14 skipping prospectively identified by liquid (L+) or tissue (T+) biopsy. Having met target enrollment of ≥60 L+ pts & ≥60 T+ pts, we report primary data. Methods: VISION Cohort A enrolled pts with advanced EGFR/ALK wt, METex14 skipping NSCLC (asymptomatic brain metastases [BM] allowed), who received oral tepotinib 500 mg QD. On-study treatment decisions were based on investigator assessment (INV) of response. Primary endpoint was objective response rate (ORR) by independent review committee (IRC) analyzed in 3 primary ITT sets: L+ and/or T+, L+, T+. 2ary endpoints included ORR by INV, duration of response (DOR), disease control rate (DCR), PFS, OS, & safety. Preplanned analyses were performed in pts with BM at baseline (BL). BL/on-treatment ctDNA plasma samples (L+) were analyzed using a 73-gene NGS panel (Guardant360). Deep molecular responses (MR), defined as 〉 75% depletion of METex14, were compared with objective responses (OR). Results: By data cut-off (1 Oct 19) 151 pts received tepotinib (safety set); 99 L+/T+, 66 L+, 60 T+ pts comprised the 3 ITT sets with ≥6-month [m] follow-up. Across treatment lines (n = 44 1L, n = 55 ≥2L), primary ORR & mPFS [95% CI] in 99 L+/T+ pts were 43% [34–54] & 8.6 m [6.9–11.0] by IRC and 56% [45–66] & 9.5 m [6.7–13.5] by INV. ORR was similar in L+ or T+ pts (table) or in T+L− pts (n = 25): 40% [21–61] by IRC and 48% [28–69] by INV. Only 2 pts were T−L+. Outcomes were also comparable in pts with BM (n = 11): IRC ORR 55% [23–83] & mPFS 10.9 m [8.0–ne]. 34/51 pts (67%) with matched BL/on-treatment L+ samples had deep MR strongly associated with clinical response: 32/34 pts (94%) with MR had disease control (INV), including 29/34 pts (85%) with OR; 2/34 pts had progressive disease. Further biomarker data will be presented. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 37/151 pts (25%). 13 pts (9%) discontinued due to TRAEs. Conclusions: Tepotinib is a promising targeted therapy with durable clinical activity and manageable toxicity in pts with METex14 skipping NSCLC L+ or T+, including pts with BM. High ORR & DCR in pts with ctDNA molecular responses support that MET inhibition in METex14+ tumor cells can lead to clinical benefit. Clinical trial information: NCT02864992 . [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.9556
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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    detail.hit.zdb_id: 604914-X
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