Tepotinib Phase II in NSCLC Harboring MET Alterations (VISION)

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02864992

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

337

Enrollment

141

Locations

Arm

101.3

Anticipated Duration (Months)

2.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will look at how effective the study drug (tepotinib) is at stopping the growth and spread of lung cancer. This study will also measure 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.

Condition or Disease	Intervention/Treatment	Phase
Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer (NSCLC) With MET Exon 14 (METex14) Skipping Alterations or MET Amplification	Drug: Tepotinib	Phase 2

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

337 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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)

Actual Study Start Date :

Sep 13, 2016

Actual Primary Completion Date :

May 16, 2022

Anticipated Study Completion Date :

Feb 20, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tepotinib	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.

Arm

Intervention/Treatment

Experimental: Tepotinib

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.

Outcome Measures

Primary Outcome Measures

Objective response as assessed by independent review committee [Baseline up to 20 months]
Objective response will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and as adjudicated by an Independent review committee. Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial 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 is 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

Objective response assessed as per Investigator [Baseline up to 20 months]
Objective response will be determined according to RECIST 1.1 and as per investigator's discretion. Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is 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.
Duration of response as assessed by independent review committee [Baseline until PD/ death within 84 days of last tumor assessment; assessed up to 20 months]
Duration of response according to RECIST 1.1 and as adjudicated by an Independent review committee is the time from when the CR/PR (whichever is first) criteria are first met until progression of disease (PD) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is 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.
Duration of response as assessed by investigator [Baseline until PD/ death within 84 days of last tumor assessment; assessed up to 20 months]
Duration of response according to RECIST 1.1 and as per investigator's discretion is the time from when the CR/PR (whichever is first) criteria are first met until progression of disease (PD) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD is 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.
Objective disease control as assessed by independent review committee [Baseline up to 20 months]
Objective disease control will be determined according to RECIST 1.1 and as adjudicated by an Independent review committee. Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by independent review committee. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is 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.
Objective disease control as assessed by investigator [Baseline up to 20 months]
Objective disease control will be determined according to RECIST 1.1 and as per investigator's discretion. Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by investigator. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD is 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.
Progression free survival as assessed by independent review committee [Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months]
Progression free survival as assessed by independent review committee is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (based on independent review) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Progression free survival as assessed by investigator [Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months]
Progression free survival as assessed by investigator is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (as assessed by investigator) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Overall survival [Baseline until death, assessed up to 20 months]
Overall survival is defined as the time (in months) from first trial treatment administration to the date of death.
Occurrence of Treatment emergent adverse event (TEAEs) and deaths [From the first dose of study drug administration until 33 days after the last dose of study drug administration, assessed up to 20 Months]
This outcome measure will be presented as the percentage of subjects with any (serious) adverse event (AE). Percentages are calculated using total number of subjects per treatment cohort as the denominator.
Percentage of subjects with of markedly abnormal clinical laboratory tests, vital signs, Electrocardiogram (ECG) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) [Baseline up to 20 months]
This outcome measure will be presented as the percentage of subjects with markedly abnormal vital sign measurements. Percentages are calculated using total number of subjects per treatment cohort as the denominator. Abnormalities in clinical laboratory tests will be measured as hematology and coagulation, biochemistry and urinalysis. Abnormalities in Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, body temperature as a part of vital signs; electrocardiogram (ECG) wave, body weight, and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), and clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis) will be assessed.
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [Baseline up to 20 months]
European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) [Baseline up to 20 months]
EuroQol Five Dimension Five Level Scale (EQ5D5L) [Baseline up to 20 months]
Plasma concentrations of the drug [pre-dose, at 1.5 hours post-dose and at 4 hours post-dose on Cycle 1, Day 1 and on Cycle 2, Day 1]
Number of subjects with markedly abnormal clinical laboratory tests (hematology and coagulation, biochemistry and urinalysis). [Baseline up to 20 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope Cancer Center	Duarte	California	United States	91010
2	Torrance Health Association	Redondo Beach	California	United States	90277
3	St Joseph Heritage Healthcare	Santa Rosa	California	United States	95403
4	Rocky Mountain Cancer Centers, LLP	Denver	Colorado	United States	80218
5	Holy Cross Hospital Inc.	Fort Lauderdale	Florida	United States	33308
6	Winship Cancer Institute	Atlanta	Georgia	United States	30322
7	University of Chicago Medical Center	Chicago	Illinois	United States	60637
8	Ingalls Hospital	Harvey	Illinois	United States	60426-3558
9	Community Regional Cancer Care	Indianapolis	Indiana	United States	46250
10	St. Louis Cancer Care, LLP	Bridgeton	Missouri	United States	63044
11	Saint Louis University Cancer Center	Saint Louis	Missouri	United States	63110
12	Saint Louis University	Saint Louis	Missouri	United States	63110
13	Regional Cancer Care Associates East Brunswick	East Brunswick	New Jersey	United States	08816
14	Hackensack University Medical Center PARTNER	Hackensack	New Jersey	United States	07601
15	The Valley Hospital	Ridgewood	New Jersey	United States	07450
16	Memorial Sloan Kettering Cancer Center - Commack	Commack	New York	United States	11725
17	Memorial Sloan Kettering Cancer Center, West Harrison Regional Outpatient Pavilion	Harrison	New York	United States	10604
18	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10022
19	UC Health Clinical Trials Office	Cincinnati	Ohio	United States	45229
20	Tennessee Oncology	Nashville	Tennessee	United States	37203
21	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232
22	Texas Oncology, P.A. - Austin	Austin	Texas	United States	78731
23	Texas Oncology, PA	Beaumont	Texas	United States	77702-1449
24	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030
25	Virginia Cancer Specialists, PC	Fairfax	Virginia	United States	22031
26	Swedish Medical Center	Seattle	Washington	United States	98104
27	Wenatchee Valley Hospital & Clinics - ATTN: Jay Johnson	Wenatchee	Washington	United States	98801
28	LKH - Universitätsklinikum der PMU Salzburg - Innere Med III/Hämatologie und Onkologie	Salzburg		Austria
29	UZ Antwerpen	Edegem		Belgium
30	CHU Ambroise Paré	Mons		Belgium
31	AZ Delta	Roeselare		Belgium
32	Peking University Cancer Hospital	Beijing		China
33	Jilin Cancer Hospital - Oncology	Changchun		China
34	Hunan Cancer Hospital	Changsha		China
35	Sichuan Cancer Hospital	Chengdu		China
36	West China Hospital, Sichuan University	Chengdu		China
37	Guangdong General Hospital	Guangzhou		China
38	Zhejiang Cancer Hospita	Hangzhou		China
39	Affiliated Tumor Hospital of Harbin Medical University	Harbin		China
40	Anhui Provincial Cancer Hospital aka West Branch of Anhui Province Hospital	Hefei City		China
41	Jinan Central Hospital	Jinan		China
42	Linyi Tumor Hospital	Linyi		China
43	Jiangsu Province Hospital	Nanjing		China
44	Shanghai Cancer Hospital, Fudan University	Shanghai		China
45	Liaoning Cancer Hospital & Institute	Shenyang		China
46	The Affiliated Cancer Hospital of Xinjiang Medical university	Urumqi		China
47	ICO - Site Paul Papin	Angers Cedex 2		France
48	Centre Hospitalier de la côte Basque	Bayonne		France
49	Centre Hospitalier de Cholet	Cholet		France
50	Centre Hospitalier Intercommunal de Créteil	Creteil cedex		France
51	Centre Hospitalier Départemental Les Oudairies	La Roche sur Yon		France
52	Hopital Albert Calmette - CHU Lille	Lille Cedex		France
53	Centre Hospitalier de Bretagne Sud	Lorient cedex		France
54	Hôpital Saint-Louis	Paris Cedex 10		France
55	Groupe Hospitalier Sud - Hôpital Haut-Lévêque	Pessac		France
56	ICO - Site René Gauducheau	Saint Herblain		France
57	Clinique Mutualiste de l'Estuaire	Saint Nazaire Cedex		France
58	CHU de Toulouse - Hôpital Larrey	Toulouse		France
59	Charite Universitaetsmedizin Berlin - Campus Charite Mitte	Berlin		Germany
60	Klinikum Chemnitz gGmbH	Chemnitz		Germany
61	Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt	Dresden		Germany
62	Universitaetsklinikum Carl Gustav Carus TU Dresden	Dresden		Germany
63	Helios Klinikum Erfurt	Erfurt		Germany
64	Asklepios Fachkliniken Muenchen-Gauting	Gauting		Germany
65	SRH Wald-Klinikum Gera gGmbH	Gera		Germany
66	Universitaetsmedizin Goettingen	Goettingen		Germany
67	Evangelisches Krankenhaus Hamm GmbH	Hamm		Germany
68	Universitaetsklinikum Heidelberg	Heidelberg		Germany
69	Universitaetsklinikum des Saarlandes	Homburg / Saar		Germany
70	POIS Leipzig GbR	Leipzig		Germany
71	Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz	Mainz		Germany
72	Pius-Hospital Oldenburg	Oldenburg		Germany
73	Soroka University Medical Center	Beer-Sheva		Israel
74	Hadassah University Hospital - Ein Kerem	Jerusalem		Israel
75	Meir Medical Center	Kfar- Saba		Israel
76	Rabin Medical Center-Beilinson Campus	Petach Tikva		Israel
77	Tel Aviv Sourasky Medical Center	Tel Aviv		Israel
78	Istituto Nazionale per la Ricerca sul Cancro di Genova	Genova		Italy
79	Fondazione IRCCS Istituto Nazionale dei Tumori	Milano		Italy
80	IEO Istituto Europeo di Oncologia	Milano		Italy
81	Seconda Università degli Studi di Napoli	Napoli		Italy
82	Azienda Ospedaliera di Padova	Padova		Italy
83	IOV - Istituto Oncologico Veneto IRCCS	Padova		Italy
84	Ospedale Santa Maria di Cà Foncello	Padova		Italy
85	Azienda Ospedaliera San Camillo Forlanini	Roma		Italy
86	Università Campus Bio-Medico di Roma	Roma		Italy
87	Istituto Clinico Humanitas	Rozzano		Italy
88	NHO Kyushu Medical Center	Fukuoka-shi		Japan
89	National Cancer Center Hospital East	Kashiwa-shi		Japan
90	Saitama Cancer Center	Kitaadachi-gun		Japan
91	Kurume University Hospital	Kurume-shi		Japan
92	NHO Shikoku Cancer Center	Matsuyama-shi		Japan
93	Nagoya University Hospital	Nagoya-shi		Japan
94	Niigata Cancer Center Hospital	Niigata-shi		Japan
95	Osaka International Cancer Institute	Osaka-shi		Japan
96	NHO Kinki-Chuo Chest Medical Center	Sakai-shi		Japan
97	Hokkaido University Hospital	Sapporo-shi		Japan
98	NHO Yamaguchi - Ube Medical Center	Ube-shi		Japan
99	Kanagawa Cancer Center	Yokohama-shi		Japan
100	Tottori University Hospital	Yonago-shi		Japan
101	Dong-A University Hospital	Busan		Korea, Republic of
102	Kosin University Gospel Hospital	Busan		Korea, Republic of
103	Kyungpook National University Medical Center	Daegu		Korea, Republic of
104	National Cancer Center	Goyang-si		Korea, Republic of
105	Chonnam National University Hwasun Hospital	Hwasun-gun		Korea, Republic of
106	Gachon University Gil Medical Center	Incheon		Korea, Republic of
107	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of
108	Korea University Anam Hospital	Seoul		Korea, Republic of
109	Samsung Medical Center	Seoul		Korea, Republic of
110	Severance Hospital, Yonsei University	Seoul		Korea, Republic of
111	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul		Korea, Republic of
112	The Catholic University of Korea, St. Vincent's Hospital	Suwon-si		Korea, Republic of
113	Antoni van Leeuwenhoek Ziekenhuis	Amsterdam		Netherlands
114	VU Medisch Centrum	Amsterdam		Netherlands
115	Universitair Medisch Centrum Groningen (UMCG) - Parent	Groningen		Netherlands
116	Centrum Pulmonologii i Torakochirurgii w Bystrej	Bystra		Poland
117	Dr n med. Slawomir Mandziuk Specjalistyczna Praktyka Lekarska	Lublin		Poland
118	NZOZ Olsztynski Osr. Onkologiczny "Kopernik" Sp.z o.o	Olsztyn		Poland
119	Przychodnia Med-Polonia Sp. z o.o.	Poznan		Poland
120	Centrum Onkologii-Instytut im. M. Sklodowskiej Curie	Warszawa		Poland
121	Hospital Universitari Quiron Dexeus	Barcelona		Spain
122	Hospital Universitari Sagrat Cor	Barcelona		Spain
123	Hospital Universitari Vall d'Hebron	Barcelona		Spain
124	Hospital General Universitario Santa Lucia	Cartagena		Spain
125	Hospital General Universitario Gregorio Marañon	Madrid		Spain
126	Hospital Universitario 12 de Octubre	Madrid		Spain
127	Hospital Universitario HM Madrid Sanchinarro	Madrid		Spain
128	Hospital Universitario La Paz	Madrid		Spain
129	Hospital Clinico Universitario Virgen de la Victoria	Malaga		Spain
130	Hospital Universitario Infanta Sofia	San Sebastian de los Reyes		Spain
131	Hospital General de Catalunya	Sant Cugat del Valles		Spain
132	Hospital Universitario Nuestra Señora de Valme	Sevilla		Spain
133	Hospital Universitario Virgen Macarena	Sevilla		Spain
134	Inselspital - Universitaetsspital Bern - Klinik und Poliklinik für Medizinische Onkologie	Bern		Switzerland
135	Universitaetsspital Zuerich - Klinik fuer Onkologie	Zuerich		Switzerland
136	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung		Taiwan
137	China Medical University Hospital	Taichung		Taiwan
138	Taichung Veterans General Hospital	Taichung		Taiwan
139	National Taiwan University Hospital	Taipei		Taiwan
140	Taipei Veterans General Hospital	Taipei		Taiwan
141	Tri-Service General Hospital	Taipei		Taiwan