Advanced (Stage IIIB/IV) Non-small Cell Lung Cancer (NSCLC) With MET Exon 14 (METex14) Skipping Alterations or MET Amplification Clinical Trial
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)
| Verified date | May 2023 |
| Source | EMD Serono |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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.
| Status | Active, not recruiting |
| Enrollment | 337 |
| Est. completion date | February 20, 2025 |
| Est. primary completion date | May 16, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Austria | LKH - Universitätsklinikum der PMU Salzburg - Innere Med III/Hämatologie und Onkologie | Salzburg | |
| Belgium | UZ Antwerpen | Edegem | |
| Belgium | UZ Antwerpen | Edegem | |
| Belgium | CHU Ambroise Paré | Mons | |
| Belgium | CHU Ambroise Paré | Mons | |
| Belgium | AZ Delta | Roeselare | |
| Belgium | AZ Delta | Roeselare | |
| China | 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 | 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 | Jiangsu Province Hospital | Nanjing | |
| China | Shanghai Cancer Hospital, Fudan University | Shanghai | |
| China | Liaoning Cancer Hospital & Institute | Shenyang | |
| China | The Affiliated Cancer Hospital of Xinjiang Medical university | Urumqi | |
| France | ICO - Site Paul Papin | Angers Cedex 2 | |
| France | ICO - Site Paul Papin | Angers Cedex 2 | Maine Et Loire |
| France | Centre Hospitalier de la côte Basque | Bayonne | |
| France | Centre Hospitalier de la côte Basque | Bayonne | Pyrenees Atlantiques |
| France | Centre Hospitalier de Cholet | Cholet | |
| France | Centre Hospitalier de Cholet | Cholet | Maine Et Loire |
| France | Centre Hospitalier Intercommunal de Créteil | Creteil cedex | |
| France | Centre Hospitalier Départemental Les Oudairies | La Roche sur Yon | |
| France | Centre Hospitalier Départemental Les Oudairies | La Roche sur Yon | Vendee |
| France | Hopital Albert Calmette - CHU Lille | Lille Cedex | Nord |
| France | Hopital Albert Calmette - CHU Lille | Lille Cedex | |
| France | Centre Hospitalier de Bretagne Sud | Lorient cedex | |
| France | Centre Hospitalier de Bretagne Sud | Lorient cedex | Morbihan |
| France | Hôpital Saint-Louis | Paris Cedex 10 | |
| France | Groupe Hospitalier Sud - Hôpital Haut-Lévêque | Pessac | |
| France | Groupe Hospitalier Sud - Hôpital Haut-Lévêque | Pessac | Gironde |
| France | ICO - Site René Gauducheau | Saint Herblain | |
| France | ICO - Site René Gauducheau | Saint Herblain | Loire Atlantique |
| France | Clinique Mutualiste de l'Estuaire | Saint Nazaire Cedex | Loire Atlantique |
| France | Clinique Mutualiste de l'Estuaire | Saint Nazaire Cedex | |
| France | CHU de Toulouse - Hôpital Larrey | Toulouse | |
| France | CHU de Toulouse - Hôpital Larrey | Toulouse | Haute Garonne |
| Germany | Charite Universitaetsmedizin Berlin - Campus Charite Mitte | Berlin | |
| 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 | Asklepios Fachkliniken Muenchen-Gauting | Gauting | |
| Germany | SRH Wald-Klinikum Gera gGmbH | Gera | |
| Germany | Universitaetsmedizin Goettingen | Goettingen | |
| Germany | Evangelisches Krankenhaus Hamm GmbH | Hamm | |
| Germany | Universitaetsklinikum Heidelberg | Heidelberg | |
| Germany | Universitaetsklinikum des Saarlandes | Homburg / Saar | |
| Germany | POIS Leipzig GbR | Leipzig | |
| Germany | POIS Leipzig GbR | Leipzig | Sachsen |
| Germany | Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz | Mainz | |
| Germany | Pius-Hospital Oldenburg | Oldenburg | |
| Israel | 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 | Tel Aviv Sourasky Medical Center | Tel Aviv | |
| Italy | Istituto Nazionale per la Ricerca sul Cancro di Genova | Genova | |
| Italy | Fondazione IRCCS Istituto Nazionale dei Tumori | Milano | |
| 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 di Padova | Padova | |
| Italy | IOV - Istituto Oncologico Veneto IRCCS | Padova | |
| Italy | Ospedale Santa Maria di Cà Foncello | Padova | |
| Italy | Azienda Ospedaliera San Camillo Forlanini | Roma | |
| Italy | Università Campus Bio-Medico di Roma | Roma | |
| Italy | Istituto Clinico Humanitas | Rozzano | |
| Japan | NHO Kyushu Medical Center | Fukuoka-shi | |
| Japan | National Cancer Center Hospital East | Kashiwa-shi | |
| Japan | Saitama Cancer Center | Kitaadachi-gun | |
| Japan | Kurume University Hospital | Kurume-shi | |
| Japan | NHO Shikoku Cancer Center | Matsuyama-shi | |
| Japan | Nagoya University Hospital | Nagoya-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 | |
| Korea, Republic of | 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 | Seoul National University Bundang Hospital | Seongnam-si | |
| Korea, Republic of | Korea University Anam Hospital | Seoul | |
| Korea, Republic of | Samsung Medical Center | Seoul | |
| Korea, Republic of | Severance Hospital, Yonsei University | Seoul | |
| 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 | |
| Netherlands | Antoni van Leeuwenhoek Ziekenhuis | Amsterdam | |
| Netherlands | VU Medisch Centrum | Amsterdam | |
| Netherlands | Universitair Medisch Centrum Groningen (UMCG) - Parent | Groningen | |
| Poland | Uniwersytecki Szpital Kliniczny w Bialymstoku - Dept of Pulmonology & Tuberculosis | Bialystok | |
| Poland | Centrum Pulmonologii i Torakochirurgii w Bystrej | Bystra | |
| Poland | Dr n med. Slawomir Mandziuk Specjalistyczna Praktyka Lekarska | Lublin | |
| Poland | NZOZ Olsztynski Osr. Onkologiczny "Kopernik" Sp.z o.o | Olsztyn | |
| Poland | Przychodnia Med-Polonia Sp. z o.o. | Poznan | |
| Poland | Przychodnia Med-Polonia Sp. z o.o. | Poznan | |
| Poland | Centrum Onkologii-Instytut im. M. Sklodowskiej Curie | Warszawa | |
| Poland | Centrum Onkologii-Instytut im. M. Sklodowskiej Curie | Warszawa | |
| Spain | Hospital Universitari Quiron Dexeus | Barcelona | |
| Spain | Hospital Universitari Sagrat Cor | Barcelona | |
| Spain | Hospital Universitari Vall d'Hebron | Barcelona | |
| Spain | Hospital Universitari Vall d'Hebron | 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 Universitario 12 de Octubre | Madrid | |
| Spain | Hospital Universitario HM Madrid Sanchinarro | Madrid | |
| Spain | Hospital Universitario HM Madrid Sanchinarro | Madrid | |
| Spain | Hospital Universitario La Paz | 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 | Hospital Universitario Virgen Macarena | Sevilla | |
| Switzerland | Inselspital - Universitaetsspital Bern - Klinik und Poliklinik für Medizinische Onkologie | Bern | |
| Switzerland | Universitaetsspital Zuerich - Klinik fuer Onkologie | Zuerich | |
| Taiwan | Kaohsiung Chang Gung Memorial Hospital | Kaohsiung | |
| Taiwan | China Medical University Hospital | Taichung | |
| Taiwan | Taichung Veterans General Hospital | Taichung | |
| Taiwan | National Taiwan University Hospital | Taipei | |
| Taiwan | Taipei Veterans General Hospital | Taipei | |
| Taiwan | Tri-Service General Hospital | Taipei | |
| United States | University Cancer & Blood Center, LLC | Athens | Georgia |
| United States | Winship Cancer Institute | Atlanta | Georgia |
| United States | Texas Oncology, P.A. - Austin | Austin | Texas |
| United States | Texas Oncology, PA | Beaumont | Texas |
| United States | Summit Medical Group | Berkeley Heights | New Jersey |
| United States | Summit Medical Group, P.A. | Berkeley Heights | New Jersey |
| United States | Center for Cancer and Blood Disorders | Bethesda | Maryland |
| United States | St. Louis Cancer Care, LLP | Bridgeton | Missouri |
| United States | University of Chicago Medical Center | Chicago | Illinois |
| United States | UC Health Clinical Trials Office | Cincinnati | Ohio |
| United States | University of Cincinnati - PARENT | Cincinnati | Ohio |
| United States | Memorial Sloan Kettering Cancer Center - Commack | Commack | New York |
| United States | Rocky Mountain Cancer Centers, LLP | Denver | Colorado |
| United States | City of Hope Cancer Center | Duarte | California |
| 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 | California Cancer Associates for Research & Excellence, Inc. | Encinitas | California |
| United States | Virginia Cancer Specialists, PC | Fairfax | Virginia |
| United States | Holy Cross Hospital Inc. | Fort Lauderdale | Florida |
| United States | Hackensack University Medical Center PARTNER | Hackensack | New Jersey |
| United States | Memorial Sloan Kettering Cancer Center, West Harrison Regional Outpatient Pavilion | Harrison | New York |
| United States | Ingalls Hospital | Harvey | Illinois |
| United States | University of Texas MD Anderson Cancer Center | Houston | Texas |
| United States | Community Regional Cancer Care | Indianapolis | Indiana |
| United States | Prospect Medical Offices, LLC | Midland Park | New Jersey |
| United States | Tennessee Oncology | Nashville | Tennessee |
| United States | Vanderbilt University Medical Center | Nashville | Tennessee |
| United States | Memorial Sloan Kettering Cancer Center | New York | New York |
| United States | St. Joseph Hospital | Orange | California |
| United States | Torrance Health Association | Redondo Beach | California |
| United States | The Valley Hospital | Ridgewood | New Jersey |
| United States | For Recruiting Locations in the United States, please Contact U.S. Medical Information | Rockland | Massachusetts |
| United States | Saint Louis University | Saint Louis | Missouri |
| United States | Saint Louis University Cancer Center | Saint Louis | Missouri |
| United States | St Joseph Heritage Healthcare | Santa Rosa | California |
| United States | Swedish Medical Center | Seattle | Washington |
| United States | H. Lee Moffitt Cancer Center and Research Institute, Inc | Tampa | Florida |
| United States | Wenatchee Valley Hospital & Clinics - ATTN: Jay Johnson | Wenatchee | Washington |
| United States | Wenatchee Valley Medical Center Oncology | Wenatchee | Washington |
| Lead Sponsor | Collaborator |
|---|---|
| EMD Serono Research & Development Institute, Inc. | Merck KGaA, Darmstadt, Germany |
United States, Austria, Belgium, China, France, Germany, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Spain, Switzerland, Taiwan,
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 — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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) | |
| Primary | 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) | |
| Primary | 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 | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | Part 1 & 2: Cohort A + B + C: Overall Survival (OS) | Time from first treatment up to end of study (approximately Month 101) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) | ||
| Secondary | 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) |