Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)

A Phase II Single-arm Trial to Investigate Tepotinib in Advanced (Locally Advanced or Metastatic) Non-small Cell Lung Cancer With METex14 Skipping Alterations or MET Amplification (VISION)

This study looked at how effective the study drug (tepotinib) was at stopping the growth and spread of lung cancer. This study also measures a number of other things including safety of the study drug and the side effects, how body processes the study drug, or how the study drug affects your quality of life. The study also has an optional pharmacogenetic research part. Pharmacogenetic research is an important way to try to understand the role of genetics in human disease and how genes impact the effectiveness of drugs, because differences in genes can change the way a person responds to a particular drug.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer (NSCLC) With MET Exon 14 (METex14) Skipping Alterations or MET Amplification; Lung Adenocarcinoma Stage IIIB/IV
• Intervention / Treatment: Drug: Tepotinib

Detailed Description

The study included 3 cohorts with one primary endpoint (Objective Response Rate). Enrollment number and completion data is changed by new cohorts.

• Study Type: Interventional
• Enrollment (Actual): 337
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Salzburg, Austria
    • LKH - Universitätsklinikum der PMU Salzburg - Innere Med III/Hämatologie und Onkologie
• Belgium
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Edegem, Belgium
    • UZ Antwerpen
  • Mons, Belgium, 7000
    • CHU Ambroise Pare
  • Mons, Belgium
    • CHU Ambroise Pare
  • Roeselare, Belgium, 8800
    • AZ Delta
  • Roeselare, Belgium
    • AZ Delta
• China
  • Beijing, China
    • Beijing Hospital
  • Beijing, China
    • Peking University Cancer Hospital
  • Changchun, China
    • Jilin Cancer Hospital - Oncology
  • Changsha, China
    • Hunan Cancer Hospital
  • Chengdu, China
    • West China Hospital, Sichuan University
  • Chengdu, China
    • Sichuan Cancer Hospital
  • Guangzhou, China
    • Guangdong General Hospital
  • Hangzhou, China
    • Zhejiang Cancer Hospita
  • Harbin, China
    • Affiliated Tumor Hospital of Harbin Medical University
  • Hefei, China
    • Anhui Provincial Cancer Hospital aka West Branch of Anhui Province Hospital
  • Jinan, China
    • Jinan Central Hospital
  • Linyi, China
    • Linyi Tumor Hospital
  • Nanjing, China
    • Jiangsu Province Hospital
  • Shanghai, China
    • Shanghai Cancer Hospital, Fudan University
  • Shenyang, China
    • Liaoning Cancer Hospital & Institute
  • Ürümqi, China
    • The Affiliated Cancer Hospital of Xinjiang Medical University
• France
  • Angers, France
    • ICO - Site Paul Papin
  • Bayonne, France
    • Centre Hospitalier de la Cote Basque
  • Cholet, France
    • Centre Hospitalier de Cholet
  • Créteil, France
    • Centre Hospitalier Intercommunal de Créteil
  • La Roche-sur-Yon, France
    • Centre Hospitalier Departemental Les Oudairies
  • Lille, France
    • Hopital Albert Calmette - CHU Lille
  • Lorient, France
    • Centre Hospitalier de Bretagne Sud
  • Paris, France
    • Hopital Saint-Louis
  • Pessac, France
    • Groupe Hospitalier Sud - Hôpital Haut-Lévêque
  • Saint-Herblain, France
    • ICO - Site René Gauducheau
  • Saint-Nazaire, France
    • Clinique Mutualiste de l'Estuaire
  • Toulouse, France
    • CHU de Toulouse - Hôpital Larrey
  • Gironde
    • Pessac, Gironde, France, 33604
      • Groupe Hospitalier Sud - Hôpital Haut-Lévêque
  • Haute Garonne
    • Toulouse, Haute Garonne, France, 31059
      • CHU de Toulouse - Hôpital Larrey
  • Loire Atlantique
    • Saint-Herblain, Loire Atlantique, France, 44805
      • ICO - Site René Gauducheau
    • Saint-Nazaire, Loire Atlantique, France, 44606
      • Clinique Mutualiste de l'Estuaire
  • Maine Et Loire
    • Angers, Maine Et Loire, France, 49055
      • ICO - Site Paul Papin
    • Cholet, Maine Et Loire, France, 49300
      • Centre Hospitalier de Cholet
  • Morbihan
    • Lorient, Morbihan, France, 56322
      • Centre Hospitalier de Bretagne Sud
  • Nord
    • Lille, Nord, France, 59037
      • Hopital Albert Calmette - CHU Lille
  • Pyrenees Atlantiques
    • Bayonne, Pyrenees Atlantiques, France, 64100
      • Centre Hospitalier de la Cote Basque
  • Vendee
    • La Roche-sur-Yon, Vendee, France, 85925
      • Centre Hospitalier Departemental Les Oudairies
• Germany
  • Berlin, Germany
    • Charite Universitaetsmedizin Berlin - Campus Charite Mitte
  • Chemnitz, Germany
    • Klinikum Chemnitz gGmbH
  • Dresden, Germany
    • Universitaetsklinikum Carl Gustav Carus TU Dresden
  • Dresden, Germany
    • Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt
  • Erfurt, Germany
    • HELIOS Klinikum Erfurt
  • Gauting, Germany
    • Asklepios Fachkliniken Muenchen-Gauting
  • Gera, Germany
    • SRH Wald-Klinikum Gera gGmbH
  • Göttingen, Germany
    • Universitaetsmedizin Goettingen
  • Hamm, Germany
    • Evangelisches Krankenhaus Hamm GmbH
  • Heidelberg, Germany
    • Universitaetsklinikum Heidelberg
  • Homburg / Saar, Germany
    • Universitaetsklinikum des Saarlandes
  • Leipzig, Germany
    • POIS Leipzig GbR
  • Mainz, Germany
    • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
  • Oldenburg, Germany
    • Pius-Hospital Oldenburg
  • Saxony
    • Leipzig, Saxony, Germany, 04357
      • POIS Leipzig GbR
• Israel
  • Beersheba, Israel
    • Soroka University Medical Center
  • Jerusalem, Israel
    • Hadassah University Hospital - Ein Kerem
  • Kfar Saba, Israel
    • Meir Medical Center
  • Petah Tikva, Israel
    • Rabin Medical Center-Beilinson Campus
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center
• Italy
  • Genova, Italy
    • Istituto Nazionale Per La Ricerca Sul Cancro Di Genova
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy
    • Fondazione IRCCS Istituto Nazionale dei Tumori
  • Milan, Italy
    • IEO Istituto Europeo di Oncologia
  • Naples, Italy
    • Seconda Università degli Studi di Napoli
  • Padova, Italy
    • Azienda Ospedaliera Di Padova
  • Padova, Italy
    • Iov - Istituto Oncologico Veneto Irccs
  • Padova, Italy
    • Ospedale Santa Maria di Cà Foncello
  • Roma, Italy
    • Azienda Ospedaliera San Camillo Forlanini
  • Roma, Italy
    • Università Campus Bio-Medico di Roma
  • Rozzano, Italy
    • Istituto Clinico Humanitas
• Japan
  • Fukuoka, Japan
    • NHO Kyushu Medical Center
  • Kashiwa-shi, Japan
    • National Cancer Center Hospital East
  • Kitaadachi-gun, Japan
    • Saitama Cancer Center
  • Kurume-shi, Japan
    • Kurume University Hospital
  • Matsuyama, Japan
    • Nho Shikoku Cancer Center
  • Nagoya, Japan
    • Nagoya University Hospital
  • Niigata, Japan
    • Niigata Cancer Center Hospital
  • Osaka, Japan
    • Osaka International Cancer Institute
  • Sakaishi, Japan
    • NHO Kinki-Chuo Chest Medical Center
  • Sapporo, Japan
    • Hokkaido University Hospital
  • Ube-shi, Japan
    • NHO Yamaguchi - Ube Medical Center
  • Yokohama, Japan
    • Kanagawa cancer center
  • Yonago-shi, Japan
    • Tottori University Hospital
• Netherlands
  • Amsterdam, Netherlands
    • VU Medisch Centrum
  • Amsterdam, Netherlands
    • Antoni van Leeuwenhoek Ziekenhuis
  • Groningen, Netherlands
    • Universitair Medisch Centrum Groningen (UMCG) - Parent
• Poland
  • Bialystok, Poland
    • Uniwersytecki Szpital Kliniczny w Bialymstoku - Dept of Pulmonology & Tuberculosis
  • Bystra, Poland
    • Centrum Pulmonologii i Torakochirurgii w Bystrej
  • Lublin, Poland
    • Dr n med. Slawomir Mandziuk Specjalistyczna Praktyka Lekarska
  • Olsztyn, Poland
    • NZOZ Olsztynski Osr. Onkologiczny "Kopernik" Sp.z o.o
  • Poznan, Poland, 60-693
    • Przychodnia Med-Polonia Sp. z o.o.
  • Poznan, Poland
    • Przychodnia Med-Polonia Sp. z o.o.
  • Warsaw, Poland
    • Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
  • Warsaw, Poland, 02-781
    • Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
• South Korea
  • Busan, South Korea
    • Kosin University Gospel Hospital
  • Busan, South Korea
    • Dong-A University Hospital
  • Daegu, South Korea
    • Kyungpook National University Medical Center
  • Goyang-si, South Korea
    • National Cancer Center
  • Hwasun-gun, South Korea
    • Chonnam National University Hwasun Hospital
  • Incheon, South Korea
    • Gachon University Gil Medical Center
  • Seongnam-si, South Korea
    • Seoul National University Bundang Hospital
  • Seoul, South Korea
    • Korea University Anam Hospital
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Severance Hospital, Yonsei University
  • Seoul, South Korea
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Suwon, South Korea
    • The Catholic University of Korea, St. Vincent'S Hospital
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain
    • Hospital Universitari Quiron Dexeus
  • Barcelona, Spain
    • Hospital Universitari Sagrat Cor
  • Cartagena, Spain
    • Hospital General Universitario Santa Lucía
  • Jerez de la Frontera, Spain
    • Hospital de Especialidades de Jerez de la Frontera - Servicio de Oncologia
  • Madrid, Spain
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Hospital Universitario La Paz
  • Madrid, Spain, 28050
    • Hospital Universitario Hm Madrid Sanchinarro
  • Madrid, Spain
    • Hospital Universitario Hm Madrid Sanchinarro
  • Málaga, Spain
    • Hospital Clinico Universitario Virgen de la Victoria
  • San Sebastián de los Reyes, Spain
    • Hospital Universitario Infanta Sofía
  • Sant Cugat del Vallès, Spain
    • Hospital General De Catalunya
  • Seville, Spain
    • Hospital Universitario Virgen Macarena
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Seville, Spain
    • Hospital Universitario Nuestra Señora de Valme
• Switzerland
  • Bern, Switzerland
    • Inselspital - Universitaetsspital Bern - Klinik und Poliklinik für Medizinische Onkologie
  • Zurich, Switzerland
    • Universitaetsspital Zuerich - Klinik fuer Onkologie
• Taiwan
  • Kaohsiung City, Taiwan
    • Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Taipei, Taiwan
    • Tri-Service General Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Cancer Center
    • Encinitas, California, United States, 92024
      • California Cancer Associates for Research & Excellence, Inc.
    • Orange, California, United States, 92868-4225
      • St. Joseph Hospital
    • Redondo Beach, California, United States, 90277
      • Torrance Health Association
    • Santa Rosa, California, United States, 95403
      • St Joseph Heritage Healthcare
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Centers, LLP
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Holy Cross Hospital Inc.
    • Tampa, Florida, United States, 33612-9497
      • H. Lee Moffitt Cancer Center and Research Institute, Inc
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Harvey, Illinois, United States, 60426-3558
      • Ingalls Hospital
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Community Regional Cancer Care
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders
  • Massachusetts
    • Rockland, Massachusetts, United States
      • For Recruiting Locations in the United States, please Contact U.S. Medical Information
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • St. Louis Cancer Care, LLP
    • St Louis, Missouri, United States, 63110
      • Saint Louis University
    • St Louis, Missouri, United States, 63110
      • Saint Louis University Cancer Center
  • New Jersey
    • Berkeley Heights, New Jersey, United States, 07922
      • Summit Medical Group
    • Berkeley Heights, New Jersey, United States, 07922
      • Summit Medical Group, P.A.
    • East Brunswick, New Jersey, United States, 08816
      • Regional Cancer Care Associates East Brunswick
    • East Brunswick, New Jersey, United States, 8816
      • Somerset Hematology Oncology Associates - Somerville Location
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center PARTNER
    • Midland Park, New Jersey, United States, 07432
      • Prospect Medical Offices, LLC
    • Ridgewood, New Jersey, United States, 07450
      • The Valley Hospital
  • New York
    • Commack, New York, United States, 11725
      • Memorial Sloan Kettering Cancer Center - Commack
    • Harrison, New York, United States, 10604
      • Memorial Sloan Kettering Cancer Center, West Harrison Regional Outpatient Pavilion
    • New York, New York, United States, 10022
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • UC Health Clinical Trials Office
    • Cincinnati, Ohio, United States, 45267-0502
      • University of Cincinnati - PARENT
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology
  • Texas
    • Austin, Texas, United States, 78731
      • Texas Oncology, P.A. - Austin
    • Beaumont, Texas, United States, 77702-1449
      • Texas Oncology, PA
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, PC
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital & Clinics - ATTN: Jay Johnson
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Medical Center Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed, written informed consent by participant or legal representative prior to any trial-specific screening procedure
• Male or female, greater than or equal to (>=) 18 years of age (or have reached the age of majority according to local laws and regulations)
• Measurable disease confirmed by an independent review committee (IRC) in accordance with RECIST version 1.1
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
• A female participant was eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential OR
• A woman of childbearing potential who agrees to use a highly effective contraception
• A male participant must agree to use and to have their female partners of childbearing potential to use a highly effective contraception
• Histologically or cytologically confirmed advanced (locally advanced or metastatic) NSCLC (all types including squamous and sarcomatoid)
• Treatment naïve participant in first-line or pretreated participant with no more than 2 lines of prior therapy
• Participants with MET alterations, namely METex14 skipping alterations in plasma and/or tissue as determined by the central laboratory or by an assay with appropriate regulatory status

Exclusion Criteria:

• Participants with characterized Epidermal Growth Factor Receptor (EGFR) activating mutations that predict sensitivity to anti-EGFR-therapy
• Participants with characterized Anaplastic Lymphoma Kinase (ALK) rearrangements that predict sensitivity to anti-ALK therapy
• Participants with symptomatic brain metastases who are neurologically unstable
• Any unresolved toxicity Grade 2 or more according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) from previous anticancer therapy
• Need for transfusion within 14 days prior to the first dose of trial treatment
• Prior chemotherapy, biological therapy, radiation therapy, hormonal therapy for anti-cancer purposes, targeted therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of trial treatment;
• Participants who have brain metastasis as the only measurable lesion
• Inadequate hematological, liver, renal, cardiac function
• Prior treatment with other agents targeting the Hepatocyte Growth Factor c(HGF/c) -Met pathway
• Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 mmHg)
• Past or current history of neoplasm other than Non-small Cell Lung Cancer (NSCLC), except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, or other cancer curatively treated and with no evidence of disease for at least 5 years
• Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the test product
• Major surgery within 28 days prior to Day 1 of trial treatment
• Known infection with human immunodeficiency virus, or an active infection with hepatitis B or hepatitis C virus
• Substance abuse, active infection, or other acute or chronic medical or psychiatric condition or laboratory abnormalities that might increase the risk associated with trial participation at the discretion of Investigators
• Known hypersensitivity to any of the trial treatment ingredients
• Legal incapacity or limited legal capacity
• Any other reason that, in the opinion of the Principal Investigator, precludes the participant from participating in the trial
• Participation in another clinical trial within the past 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Part 1: Cohort A: METex14 Skipping Alterations; Participants received 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.	Drug: Tepotinib; Subjects will receive 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.
Other: Part 1: Cohort B: MET Amplification; Participants received 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.	Drug: Tepotinib; Subjects will receive 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.
Other: Part 2: Cohort C: Confirmatory Part for METex14 Skipping Alterations; Participants received 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.	Drug: Tepotinib; Subjects will receive 500 milligram (mg) of tepotinib once daily in cycles of 21-day duration until disease progression, death, adverse event (AE) leading to discontinuation or withdrawal of consent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Cohort A: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Independent Review Committee (IRC)	Objective response will be determined according to RECIST 1.1 and as per IRC. Objective response was defined as number of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Time from first treatment up to data cutoff (approximately Month 66)
Part 1: Cohort B: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC)	Objective response will be determined according to RECIST 1.1 and as per IRC. Objective response was defined as number of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Time from first treatment up to data cutoff (approximately Month 66)
Part 2: Cohort C: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC)	Objective response will be determined according to RECIST 1.1 and as per IRC. Objective response was defined as number of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.	Time from first treatment up to data cutoff (approximately Month 66)

Secondary Outcome Measures

Outcome Measure	Time Frame
Part 1 & 2: Cohort A + B + C: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B + C: Duration of Response (DOR) Assessed by Investigator	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B + C: Objective Disease Control Rate Assessed by IRC	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B + C: Objective Disease Control Rate Assessed by Investigator	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B + C: Progression-free Survival by IRC Assessment	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B +C: Progression-free Survival by Investigator Assessment	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B + C: Overall Survival (OS)	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B + C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B +C: Number of Participants With Markedly Abnormal Clinical Laboratory Tests	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B + C: Number of Participants With Markedly Abnormal Vital Signs and Physical Examination	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B + C: Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiogram (ECG)	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B + C: Change From Baseline in Euro Quality of Life Questionnaire With 5 Questions Alternatives (EQ5D-5L) Summary Score	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B + C: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)	Time from first treatment up to end of study (approximately Month 101)
Part 1 & 2: Cohort A + B + C: Quality of Life (QoL) Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)	Time from first treatment up to end of study (approximately Month 101)

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc, a business of Merck KGaA, Darmstadt, Germany

Publications and helpful links

General Publications

• Xiong W, Hietala SF, Nyberg J, Papasouliotis O, Johne A, Berghoff K, Goteti K, Dong J, Girard P, Venkatakrishnan K, Strotmann R. Exposure-response analyses for the MET inhibitor tepotinib including patients in the pivotal VISION trial: support for dosage recommendations. Cancer Chemother Pharmacol. 2022 Jul;90(1):53-69. doi: 10.1007/s00280-022-04441-3. Epub 2022 Jun 30.
• Paik PK, Felip E, Veillon R, Sakai H, Cortot AB, Garassino MC, Mazieres J, Viteri S, Senellart H, Van Meerbeeck J, Raskin J, Reinmuth N, Conte P, Kowalski D, Cho BC, Patel JD, Horn L, Griesinger F, Han JY, Kim YC, Chang GC, Tsai CL, Yang JC, Chen YM, Smit EF, van der Wekken AJ, Kato T, Juraeva D, Stroh C, Bruns R, Straub J, Johne A, Scheele J, Heymach JV, Le X. Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations. N Engl J Med. 2020 Sep 3;383(10):931-943. doi: 10.1056/NEJMoa2004407. Epub 2020 May 29.
• Xiong W, Papasouliotis O, Jonsson EN, Strotmann R, Girard P. Population pharmacokinetic analysis of tepotinib, an oral MET kinase inhibitor, including data from the VISION study. Cancer Chemother Pharmacol. 2022 May;89(5):655-669. doi: 10.1007/s00280-022-04423-5. Epub 2022 Apr 6.
• Hallick J, Baird AM, Falchook G, Le X, Hong D, Viteri S, Raskin J, Reinmuth N, Vlassak S, Militaru M, Paik PK. Plain language summary of the development of tepotinib: a treatment for a subtype of non-small cell lung cancer called MET exon 14 skipping. Future Oncol. 2023 Mar;19(10):683-696. doi: 10.2217/fon-2022-1035. Epub 2023 Mar 31.
• Kato T, Yang JC, Ahn MJ, Sakai H, Morise M, Chen YM, Han JY, Yang JJ, Zhao J, Hsia TC, Berghoff K, Bruns R, Vioix H, Lang S, Johne A, Le X, Paik PK. Efficacy and safety of tepotinib in Asian patients with advanced NSCLC with MET exon 14 skipping enrolled in VISION. Br J Cancer. 2024 Jun;130(10):1679-1686. doi: 10.1038/s41416-024-02615-9. Epub 2024 Apr 4.
• Le X, Paz-Ares LG, Van Meerbeeck J, Viteri S, Galvez CC, Smit EF, Garassino M, Veillon R, Baz DV, Pradera JF, Sereno M, Kozuki T, Kim YC, Yoo SS, Han JY, Kang JH, Son CH, Choi YJ, Stroh C, Juraeva D, Vioix H, Bruns R, Otto G, Johne A, Paik PK. Tepotinib in patients with non-small cell lung cancer with high-level MET amplification detected by liquid biopsy: VISION Cohort B. Cell Rep Med. 2023 Nov 21;4(11):101280. doi: 10.1016/j.xcrm.2023.101280. Epub 2023 Nov 8.
• Mazieres J, Paik PK, Garassino MC, Le X, Sakai H, Veillon R, Smit EF, Cortot AB, Raskin J, Viteri S, Wu YL, Yang JCH, Ahn MJ, Ma R, Zhao J, O'Brate A, Berghoff K, Bruns R, Otto G, Johne A, Felip E, Thomas M. 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. JAMA Oncol. 2023 Sep 1;9(9):1260-1266. doi: 10.1001/jamaoncol.2023.1962.

Helpful Links

• US Medical Information website, Medical Resources
• Redacted Clinical study report, redacted clinical study protocol and redacted statistical analysis plan for this study is also available at the HC-PRCI portal (Health Canada-Public release of clinical information)
• Targeting MET Clinical Trial Program
• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2016
• Primary Completion (Actual): May 16, 2022
• Study Completion (Estimated): April 30, 2026

Study Registration Dates

• First Submitted: July 29, 2016
• First Submitted That Met QC Criteria: August 9, 2016
• First Posted (Estimated): August 12, 2016

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: lung; NSCLC; cancer; stage III; non-small cell lung cancer; MET amplification; adenocarcinoma; advanced non-small cell lung cancer; cMET; tumor; neoplasm; pulmonary; stage IV; c-Met; METex14; MET exon 14
• Additional Relevant MeSH Terms: Neoplasms by Site; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma; Antineoplastic Agents; tepotinib
• Other Study ID Numbers: MS200095-0022; 2015-005696-24 (EudraCT Number); 2024-512003-39-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
• IPD Sharing Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• IPD Sharing Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR