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Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)

Primary Purpose

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

Status

Active

Phase

Phase 2

Locations

International

Study Type

Interventional

Intervention

Tepotinib

About this trial

This is an interventional treatment trial for Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer (NSCLC) With MET Exon 14 (METex14) Skipping Alterations or MET Amplification focused on measuring lung, neoplasm, cancer, tumor, adenocarcinoma, MET exon 14, METex14, pulmonary, stage III, stage IV, c-Met, cMET, NSCLC, advanced non-small cell lung cancer, MET amplification, non-small cell lung cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Signed, written informed consent by subject or legal representative prior to any trial-specific screening procedure
Male or female, greater than or equal to (>=) 18 years of age (or having 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 subject is 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 subject 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 patients in first-line or pretreated patients with no more than 2 lines of prior therapy
Subjects 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:

Subjects with characterized Epidermal Growth Factor Receptor (EGFR) activating mutations that predict sensitivity to anti-EGFR-therapy
Subjects with characterized Anaplastic Lymphoma Kinase (ALK) rearrangements that predict sensitivity to anti-ALK therapy
Subjects 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;
Subjects 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 subject from participating in the trial
Participation in another clinical trial within the past 30 days

Sites / Locations

City of Hope Cancer Center
California Cancer Associates for Research & Excellence, Inc.
St. Joseph Hospital
Torrance Health Association
St Joseph Heritage Healthcare
Rocky Mountain Cancer Centers, LLP
Holy Cross Hospital Inc.
H. Lee Moffitt Cancer Center and Research Institute, Inc
University Cancer & Blood Center, LLC
Winship Cancer Institute
University of Chicago Medical Center
Ingalls Hospital
Community Regional Cancer Care
Center for Cancer and Blood Disorders
For Recruiting Locations in the United States, please Contact U.S. Medical Information
St. Louis Cancer Care, LLP
Saint Louis University Cancer Center
Saint Louis University
Summit Medical Group, P.A.
Summit Medical Group
Regional Cancer Care Associates East Brunswick
Somerset Hematology Oncology Associates - Somerville Location
Hackensack University Medical Center PARTNER
Prospect Medical Offices, LLC
The Valley Hospital
Memorial Sloan Kettering Cancer Center - Commack
Memorial Sloan Kettering Cancer Center, West Harrison Regional Outpatient Pavilion
Memorial Sloan Kettering Cancer Center
UC Health Clinical Trials Office
University of Cincinnati - PARENT
Tennessee Oncology
Vanderbilt University Medical Center
Texas Oncology, P.A. - Austin
Texas Oncology, PA
University of Texas MD Anderson Cancer Center
Virginia Cancer Specialists, PC
Swedish Medical Center
Wenatchee Valley Hospital & Clinics - ATTN: Jay Johnson
Wenatchee Valley Medical Center Oncology
LKH - Universitätsklinikum der PMU Salzburg - Innere Med III/Hämatologie und Onkologie
UZ Antwerpen
UZ Antwerpen
CHU Ambroise Paré
CHU Ambroise Paré
AZ Delta
AZ Delta
Beijing Hospital
Peking University Cancer Hospital
Jilin Cancer Hospital - Oncology
Hunan Cancer Hospital
Sichuan Cancer Hospital
West China Hospital, Sichuan University
Guangdong General Hospital
Zhejiang Cancer Hospita
Affiliated Tumor Hospital of Harbin Medical University
Anhui Provincial Cancer Hospital aka West Branch of Anhui Province Hospital
Jinan Central Hospital
Linyi Tumor Hospital
Jiangsu Province Hospital
Shanghai Cancer Hospital, Fudan University
Liaoning Cancer Hospital & Institute
The Affiliated Cancer Hospital of Xinjiang Medical university
Groupe Hospitalier Sud - Hôpital Haut-Lévêque
CHU de Toulouse - Hôpital Larrey
ICO - Site René Gauducheau
Clinique Mutualiste de l'Estuaire
ICO - Site Paul Papin
Centre Hospitalier de Cholet
Centre Hospitalier de Bretagne Sud
Hopital Albert Calmette - CHU Lille
Centre Hospitalier de la côte Basque
Centre Hospitalier Départemental Les Oudairies
ICO - Site Paul Papin
Centre Hospitalier de la côte Basque
Centre Hospitalier de Cholet
Centre Hospitalier Intercommunal de Créteil
Centre Hospitalier Départemental Les Oudairies
Hopital Albert Calmette - CHU Lille
Centre Hospitalier de Bretagne Sud
Hôpital Saint-Louis
Groupe Hospitalier Sud - Hôpital Haut-Lévêque
ICO - Site René Gauducheau
Clinique Mutualiste de l'Estuaire
CHU de Toulouse - Hôpital Larrey
POIS Leipzig GbR
Charite Universitaetsmedizin Berlin - Campus Charite Mitte
Klinikum Chemnitz gGmbH
For Recruiting Locations outside US, please Contact Merck KGaA Communication Center
Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt
Universitaetsklinikum Carl Gustav Carus TU Dresden
Helios Klinikum Erfurt
Asklepios Fachkliniken Muenchen-Gauting
SRH Wald-Klinikum Gera gGmbH
Universitaetsmedizin Goettingen
Evangelisches Krankenhaus Hamm GmbH
Universitaetsklinikum Heidelberg
Universitaetsklinikum des Saarlandes
POIS Leipzig GbR
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
Pius-Hospital Oldenburg
Soroka University Medical Center
Hadassah University Hospital - Ein Kerem
Meir Medical Center
Rabin Medical Center-Beilinson Campus
Tel Aviv Sourasky Medical Center
Istituto Nazionale per la Ricerca sul Cancro di Genova
Fondazione IRCCS Istituto Nazionale dei Tumori
Fondazione IRCCS Istituto Nazionale dei Tumori
IEO Istituto Europeo di Oncologia
Seconda Università degli Studi di Napoli
Azienda Ospedaliera di Padova
IOV - Istituto Oncologico Veneto IRCCS
Ospedale Santa Maria di Cà Foncello
Azienda Ospedaliera San Camillo Forlanini
Università Campus Bio-Medico di Roma
Istituto Clinico Humanitas
NHO Kyushu Medical Center
National Cancer Center Hospital East
Saitama Cancer Center
Kurume University Hospital
NHO Shikoku Cancer Center
Nagoya University Hospital
Niigata Cancer Center Hospital
Osaka International Cancer Institute
NHO Kinki-Chuo Chest Medical Center
Hokkaido University Hospital
NHO Yamaguchi - Ube Medical Center
Kanagawa Cancer Center
Tottori University Hospital
Dong-A University Hospital
Kosin University Gospel Hospital
Kyungpook National University Medical Center
National Cancer Center
Chonnam National University Hwasun Hospital
Gachon University Gil Medical Center
Seoul National University Bundang Hospital
Korea University Anam Hospital
Samsung Medical Center
Severance Hospital, Yonsei University
The Catholic University of Korea, Seoul St. Mary's Hospital
The Catholic University of Korea, St. Vincent's Hospital
Antoni van Leeuwenhoek Ziekenhuis
VU Medisch Centrum
Universitair Medisch Centrum Groningen (UMCG) - Parent
Uniwersytecki Szpital Kliniczny w Bialymstoku - Dept of Pulmonology & Tuberculosis
Centrum Pulmonologii i Torakochirurgii w Bystrej
Dr n med. Slawomir Mandziuk Specjalistyczna Praktyka Lekarska
NZOZ Olsztynski Osr. Onkologiczny "Kopernik" Sp.z o.o
Przychodnia Med-Polonia Sp. z o.o.
Przychodnia Med-Polonia Sp. z o.o.
Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
Centrum Onkologii-Instytut im. M. Sklodowskiej Curie
Hospital Universitari Vall d'Hebron
Hospital Universitari Quiron Dexeus
Hospital Universitari Sagrat Cor
Hospital Universitari Vall d'Hebron
Hospital General Universitario Santa Lucia
Hospital de Especialidades de Jerez de la Frontera - Servicio de Oncologia
Hospital Universitario HM Madrid Sanchinarro
Hospital General Universitario Gregorio Marañon
Hospital Universitario 12 de Octubre
Hospital Universitario HM Madrid Sanchinarro
Hospital Universitario La Paz
Hospital Clinico Universitario Virgen de la Victoria
Hospital Universitario Infanta Sofia
Hospital General de Catalunya
Hospital Universitario Virgen Macarena
Hospital Universitario Nuestra Señora de Valme
Hospital Universitario Virgen Macarena
Inselspital - Universitaetsspital Bern - Klinik und Poliklinik für Medizinische Onkologie
Universitaetsspital Zuerich - Klinik fuer Onkologie
Kaohsiung Chang Gung Memorial Hospital
China Medical University Hospital
Taichung Veterans General Hospital
National Taiwan University Hospital
Taipei Veterans General Hospital
Tri-Service General Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Other

Arm Label

Part 1: Cohort A: METex14 Skipping Alterations

Part 1: Cohort B: MET Amplification

Part 2: Cohort C: Confirmatory Part for METex14 Skipping Alterations

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Part 1: Cohort B: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC)

Part 2: Cohort C: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC)

Secondary Outcome Measures

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

Part 1 & 2: Cohort A + B + C: Duration of Response (DOR) Assessed by Investigator

Part 1 & 2: Cohort A + B + C: Objective Disease Control Rate Assessed by IRC

Part 1 & 2: Cohort A + B + C: Objective Disease Control Rate Assessed by Investigator

Part 1 & 2: Cohort A + B + C: Progression-free Survival by IRC Assessment

Part 1 & 2: Cohort A + B +C: Progression-free Survival by Investigator Assessment

Part 1 & 2: Cohort A + B + C: Overall Survival (OS)

Part 1 & 2: Cohort A + B + C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death

Part 1 & 2: Cohort A + B +C: Number of Participants With Markedly Abnormal Clinical Laboratory Tests

Part 1 & 2: Cohort A + B + C: Number of Participants With Markedly Abnormal Vital Signs and Physical Examination

Part 1 & 2: Cohort A + B + C: Number of Participants With Clinically Significant Change From Baseline in 12-Lead Electrocardiogram (ECG)

Part 1 & 2: Cohort A + B + C: Change From Baseline in Euro Quality of Life Questionnaire With 5 Questions Alternatives (EQ5D-5L) Summary Score

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)

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)

Full Information

NCT ID

NCT02864992

First Posted

July 29, 2016

Last Updated

May 15, 2023

Sponsor

EMD Serono Research & Development Institute, Inc.

Collaborators

Merck KGaA, Darmstadt, Germany

1. Study Identification

Unique Protocol Identification Number

NCT02864992

Brief Title

Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

May 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

September 13, 2016 (Actual)

Primary Completion Date

May 16, 2022 (Actual)

Study Completion Date

February 20, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

EMD Serono Research & Development Institute, Inc.

Collaborators

Merck KGaA, Darmstadt, Germany

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

lung, neoplasm, cancer, tumor, adenocarcinoma, MET exon 14, METex14, pulmonary, stage III, stage IV, c-Met, cMET, NSCLC, advanced non-small cell lung cancer, MET amplification, non-small cell lung cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

337 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Cohort A: METex14 Skipping Alterations

Arm Type

Other

Arm Description

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.

Arm Title

Part 1: Cohort B: MET Amplification

Arm Type

Other

Arm Description

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.

Arm Title

Part 2: Cohort C: Confirmatory Part for METex14 Skipping Alterations

Arm Type

Other

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Tepotinib

Intervention Description

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.

Primary Outcome Measure Information:

Title

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)

Description

Time Frame

Time from first treatment up to data cutoff (approximately Month 66)

Title

Part 1: Cohort B: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC)

Description

Time Frame

Time from first treatment up to data cutoff (approximately Month 66)

Title

Part 2: Cohort C: Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 as Assessed by Independent Review Committee (IRC)

Description

Time Frame

Time from first treatment up to data cutoff (approximately Month 66)

Secondary Outcome Measure Information:

Title

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 Frame