Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)
- Conditions
- Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer (NSCLC) With MET Exon 14 (METex14) Skipping Alterations or MET AmplificationLung Adenocarcinoma Stage IIIB/IV
- Interventions
- Registration Number
- NCT02864992
- Brief Summary
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.
- Detailed Description
The study included 3 cohorts with one primary endpoint (Objective Response Rate). Enrollment number and completion data is changed by new cohorts.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 337
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Part 1: Cohort A: METex14 Skipping Alterations Tepotinib 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. Part 1: Cohort B: MET Amplification Tepotinib 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. Part 2: Cohort C: Confirmatory Part for METex14 Skipping Alterations Tepotinib 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.
- Primary Outcome Measures
Name Time Method 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) Time from first treatment up to data cutoff (approximately Month 66) 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.
Part 1: Cohort B: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC) Time from first treatment up to data cutoff (approximately Month 66) 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.
Part 2: Cohort C: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC) Time from first treatment up to data cutoff (approximately Month 66) 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.
- Secondary Outcome Measures
Name Time Method 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: 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: 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: 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: 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: 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: 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 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 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: 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: 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)
Trial Locations
- Locations (157)
Holy Cross Hospital Inc.
🇺🇸Fort Lauderdale, Florida, United States
Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Wenatchee Valley Hospital & Clinics - ATTN: Jay Johnson
🇺🇸Wenatchee, Washington, United States
Wenatchee Valley Medical Center Oncology
🇺🇸Wenatchee, Washington, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Swedish Medical Center
🇺🇸Seattle, Washington, United States
City of Hope Cancer Center
🇺🇸Duarte, California, United States
California Cancer Associates for Research & Excellence, Inc.
🇺🇸Encinitas, California, United States
St. Joseph Hospital
🇺🇸Orange, California, United States
Torrance Health Association
🇺🇸Redondo Beach, California, United States
Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
University Cancer & Blood Center, LLC
🇺🇸Athens, Georgia, United States
Ingalls Hospital
🇺🇸Harvey, Illinois, United States
For Recruiting Locations in the United States, please Contact U.S. Medical Information
🇺🇸Rockland, Massachusetts, United States
St. Louis Cancer Care, LLP
🇺🇸Bridgeton, Missouri, United States
Saint Louis University Cancer Center
🇺🇸Saint Louis, Missouri, United States
Summit Medical Group, P.A.
🇺🇸Berkeley Heights, New Jersey, United States
Hackensack University Medical Center PARTNER
🇺🇸Hackensack, New Jersey, United States
Summit Medical Group
🇺🇸Berkeley Heights, New Jersey, United States
Regional Cancer Care Associates East Brunswick
🇺🇸East Brunswick, New Jersey, United States
Somerset Hematology Oncology Associates - Somerville Location
🇺🇸East Brunswick, New Jersey, United States
Prospect Medical Offices, LLC
🇺🇸Midland Park, New Jersey, United States
The Valley Hospital
🇺🇸Ridgewood, New Jersey, United States
Memorial Sloan Kettering Cancer Center, West Harrison Regional Outpatient Pavilion
🇺🇸Harrison, New York, United States
Memorial Sloan Kettering Cancer Center - Commack
🇺🇸Commack, New York, United States
Texas Oncology, P.A. - Austin
🇺🇸Austin, Texas, United States
Texas Oncology, PA
🇺🇸Beaumont, Texas, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
LKH - Universitätsklinikum der PMU Salzburg - Innere Med III/Hämatologie und Onkologie
🇦🇹Salzburg, Austria
Beijing Hospital
🇨🇳Beijing, China
Peking University Cancer Hospital
🇨🇳Beijing, China
Jilin Cancer Hospital - Oncology
🇨🇳Changchun, China
Hunan Cancer Hospital
🇨🇳Changsha, China
Sichuan Cancer Hospital
🇨🇳Chengdu, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
UZ Antwerpen
🇧🇪Edegem, Belgium
CHU Ambroise Paré
🇧🇪Mons, Belgium
AZ Delta
🇧🇪Roeselare, Belgium
Guangdong General Hospital
🇨🇳Guangzhou, China
Zhejiang Cancer Hospita
🇨🇳Hangzhou, China
Affiliated Tumor Hospital of Harbin Medical University
🇨🇳Harbin, China
Anhui Provincial Cancer Hospital aka West Branch of Anhui Province Hospital
🇨🇳Hefei City, China
Jinan Central Hospital
🇨🇳Jinan, China
Linyi Tumor Hospital
🇨🇳Linyi, China
Shanghai Cancer Hospital, Fudan University
🇨🇳Shanghai, China
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang, China
The Affiliated Cancer Hospital of Xinjiang Medical university
🇨🇳Urumqi, China
CHU de Toulouse - Hôpital Larrey
🇫🇷Toulouse, France
ICO - Site René Gauducheau
🇫🇷Saint Herblain, France
Groupe Hospitalier Sud - Hôpital Haut-Lévêque
🇫🇷Pessac, France
Clinique Mutualiste de l'Estuaire
🇫🇷Saint Nazaire Cedex, France
ICO - Site Paul Papin
🇫🇷Angers Cedex 2, France
Centre Hospitalier de Cholet
🇫🇷Cholet, France
Centre Hospitalier de Bretagne Sud
🇫🇷Lorient cedex, France
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
🇩🇪Berlin, Germany
Hopital Albert Calmette - CHU Lille
🇫🇷Lille Cedex, France
Centre Hospitalier de la côte Basque
🇫🇷Bayonne, France
Centre Hospitalier Départemental Les Oudairies
🇫🇷La Roche sur Yon, France
Centre Hospitalier Intercommunal de Créteil
🇫🇷Creteil cedex, France
Hôpital Saint-Louis
🇫🇷Paris Cedex 10, France
POIS Leipzig GbR
🇩🇪Leipzig, Germany
Klinikum Chemnitz gGmbH
🇩🇪Chemnitz, Germany
For Recruiting Locations outside US, please Contact Merck KGaA Communication Center
🇩🇪Darmstadt, Germany
Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt
🇩🇪Dresden, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
🇩🇪Dresden, Germany
Helios Klinikum Erfurt
🇩🇪Erfurt, Germany
Universitaetsmedizin Goettingen
🇩🇪Goettingen, Germany
Asklepios Fachkliniken Muenchen-Gauting
🇩🇪Gauting, Germany
SRH Wald-Klinikum Gera gGmbH
🇩🇪Gera, Germany
Evangelisches Krankenhaus Hamm GmbH
🇩🇪Hamm, Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitaetsklinikum des Saarlandes
🇩🇪Homburg / Saar, Germany
Soroka University Medical Center
🇮🇱Beer-Sheva, Israel
Hadassah University Hospital - Ein Kerem
🇮🇱Jerusalem, Israel
Meir Medical Center
🇮🇱Kfar- Saba, Israel
Rabin Medical Center-Beilinson Campus
🇮🇱Petach Tikva, Israel
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
🇩🇪Mainz, Germany
Pius-Hospital Oldenburg
🇩🇪Oldenburg, Germany
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Istituto Nazionale per la Ricerca sul Cancro di Genova
🇮🇹Genova, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
IEO Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Seconda Università degli Studi di Napoli
🇮🇹Napoli, Italy
Azienda Ospedaliera San Camillo Forlanini
🇮🇹Roma, Italy
Università Campus Bio-Medico di Roma
🇮🇹Roma, Italy
IOV - Istituto Oncologico Veneto IRCCS
🇮🇹Padova, Italy
Azienda Ospedaliera di Padova
🇮🇹Padova, Italy
Ospedale Santa Maria di Cà Foncello
🇮🇹Padova, Italy
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Japan
NHO Kyushu Medical Center
🇯🇵Fukuoka-shi, Japan
Nagoya University Hospital
🇯🇵Nagoya-shi, Japan
Saitama Cancer Center
🇯🇵Kitaadachi-gun, Japan
Kurume University Hospital
🇯🇵Kurume-shi, Japan
NHO Shikoku Cancer Center
🇯🇵Matsuyama-shi, Japan
Niigata Cancer Center Hospital
🇯🇵Niigata-shi, Japan
Osaka International Cancer Institute
🇯🇵Osaka-shi, Japan
NHO Kinki-Chuo Chest Medical Center
🇯🇵Sakai-shi, Japan
Hokkaido University Hospital
🇯🇵Sapporo-shi, Japan
NHO Yamaguchi - Ube Medical Center
🇯🇵Ube-shi, Japan
Kanagawa Cancer Center
🇯🇵Yokohama-shi, Japan
Tottori University Hospital
🇯🇵Yonago-shi, Japan
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Kosin University Gospel Hospital
🇰🇷Busan, Korea, Republic of
Kyungpook National University Medical Center
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun-gun, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, St. Vincent's Hospital
🇰🇷Suwon-si, Korea, Republic of
Antoni van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
VU Medisch Centrum
🇳🇱Amsterdam, Netherlands
Universitair Medisch Centrum Groningen (UMCG) - Parent
🇳🇱Groningen, Netherlands
Uniwersytecki Szpital Kliniczny w Bialymstoku - Dept of Pulmonology & Tuberculosis
🇵🇱Bialystok, Poland
Dr n med. Slawomir Mandziuk Specjalistyczna Praktyka Lekarska
🇵🇱Lublin, Poland
Centrum Pulmonologii i Torakochirurgii w Bystrej
🇵🇱Bystra, Poland
NZOZ Olsztynski Osr. Onkologiczny "Kopernik" Sp.z o.o
🇵🇱Olsztyn, Poland
Przychodnia Med-Polonia Sp. z o.o.
🇵🇱Poznan, Poland
Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
🇵🇱Warszawa, Poland
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitari Quiron Dexeus
🇪🇸Barcelona, Spain
Hospital Universitari Sagrat Cor
🇪🇸Barcelona, Spain
Hospital General Universitario Santa Lucia
🇪🇸Cartagena, Spain
Hospital de Especialidades de Jerez de la Frontera - Servicio de Oncologia
🇪🇸Jerez de la Frontera, Spain
Hospital General Universitario Gregorio Marañon
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Hospital Universitario Infanta Sofia
🇪🇸San Sebastian de los Reyes, Spain
Hospital General de Catalunya
🇪🇸Sant Cugat del Valles, Spain
Hospital Universitario Nuestra Señora de Valme
🇪🇸Sevilla, Spain
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Spain
Inselspital - Universitaetsspital Bern - Klinik und Poliklinik für Medizinische Onkologie
🇨🇭Bern, Switzerland
Universitaetsspital Zuerich - Klinik fuer Onkologie
🇨🇭Zuerich, Switzerland
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Hospital Universitario HM Madrid Sanchinarro
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University
🇰🇷Seoul, Korea, Republic of
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
UC Health Clinical Trials Office
🇺🇸Cincinnati, Ohio, United States
University of Cincinnati - PARENT
🇺🇸Cincinnati, Ohio, United States
Rocky Mountain Cancer Centers, LLP
🇺🇸Denver, Colorado, United States
Community Regional Cancer Care
🇺🇸Indianapolis, Indiana, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
H. Lee Moffitt Cancer Center and Research Institute, Inc
🇺🇸Tampa, Florida, United States
Center for Cancer and Blood Disorders
🇺🇸Bethesda, Maryland, United States
St Joseph Heritage Healthcare
🇺🇸Santa Rosa, California, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Jiangsu Province Hospital
🇨🇳Nanjing, China