A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2)

• ClinicalTrials.gov Identifier: NCT03940703
• Recruitment Status: Active, not recruiting
• First Posted: May 7, 2019
• Last Update Posted: November 30, 2023
• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborator: Merck KGaA, Darmstadt, Germany
• Information provided by (Responsible Party): EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Description

Brief Summary:

This study will assess the antitumor activity, safety, tolerability, and pharmacokinetics (PK) of the Mesenchymal-epithelial Transition Factor (MET) inhibitor tepotinib combined with the 3rd generation EGFR inhibitor osimertinib in participants with advanced or metastatic non-small cell lung cancer (NSCLC).

Condition or disease	Intervention/treatment	Phase
Non-small Cell Lung Cancer	Drug: Tepotinib; Drug: Osimertinib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 120 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Two-arm Study to Investigate Tepotinib Combined With Osimertinib in MET Amplified, Advanced or Metastatic NSCLC Harboring Activating EGFR Mutations and Having Acquired Resistance to Prior Osimertinib Therapy (INSIGHT 2)
• Actual Study Start Date: September 19, 2019
• Actual Primary Completion Date: May 11, 2023
• Estimated Study Completion Date: May 27, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Tepotinib and Osimertinib; Participants will receive a combination of tepotinib and osimertinib. The combination will be applied in cycles of 21 days until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Drug: Tepotinib; Participants will be administered Tepotinib orally once daily at an initial dose of 500 milligram (mg). A safety monitoring committee (SMC) may decide to confirm or adapt the dose.; Drug: Osimertinib; Participants will receive Osimertinib at a dose of 80 mg orally once daily.; Other Name: Tagrisso®
Experimental: Tepotinib Mono-therapy; Participants will receive once daily dose of tepotinib. The mono therapy will be applied in cycles of 21 days until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.	Drug: Tepotinib; Participants will be administered Tepotinib orally once daily at an initial dose of 500 milligram (mg). A safety monitoring committee (SMC) may decide to confirm or adapt the dose.

Outcome Measures

Primary Outcome Measures :

1. Safety run-in: Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version (NCI-CTCAE v 5.0) [ Time Frame: Up to Day 21 of Cycle 1 (each Cycle is of 21 days) ]
2. Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as per Independent Review Committee for Combined Therapy in Participants With MET Amplification Determined Centrally by Fluorescence in situ Hybridization(FISH) [ Time Frame: Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 38 months) ]
   Participants are identified as having an objective response if they achieve either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progression disease (PD) according to determined according to RECIST 1.1 as adjudicated by the IRC. CR: Complete Response defined as disappearance of all target and non target lesions and any pathological lymph nodes (whether target or non target) must have reduction in short axis to less than (<) 10 mm. Partial response defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.

Secondary Outcome Measures :

1. Objective Response According to RECIST Version 1.1 as per IRC for Combined Therapy in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing [ Time Frame: Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 42 months) ]
   Participants are identified as having an objective response if they achieve either a confirmed CR or PR from first administration of study treatment to first observation of PD according to determined according to RECIST 1.1 as adjudicated by the IRC. CR: Complete Response defined as disappearance of all target and non target lesions and any pathological lymph nodes (whether target or non target) must have reduction in short axis to less than (<) 10 mm. Partial response defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
2. Objective Response According to RECIST Version 1.1 as per IRC for Tepotinib Monotherapy in Participants With MET Amplification Determined Centrally by FISH [ Time Frame: Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 42 months) ]
   Participants are identified as having an objective response if they achieve either a confirmed CR or PR from first administration of study treatment to first observation of PD according to determined according to RECIST 1.1 as adjudicated by the IRC. CR: Complete Response defined as disappearance of all target and non target lesions and any pathological lymph nodes (whether target or non target) must have reduction in short axis to less than (<) 10 mm. Partial response defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
3. Number of Participants With Adverse Events (AEs) and Treatment-Related Adverse Events According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, and Deaths [ Time Frame: Baseline up to 30 days after the last dose of study treatment ]
4. Percentage of Participants With Abnormal greater Than or Equal to (>=) Grade 3 Laboratory Findings [ Time Frame: Baseline up to 30 days after the last dose of study treatment ]
5. Percentage of Participants With Abnormal Vital Signs, Electrocardiograms (ECGs) and Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline up to 30 days after the last dose of study treatment ]
   Percentage of participants with abnormalities in vital signs; clinically significant electrocardiograms (ECGs), change in body weight and change in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) will be analyzed.
6. Objective Response According to RECIST Version 1.1 Assessed by Investigator for Combined Therapy in Participants with MET Amplification Determined Centrally by FISH [ Time Frame: Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 42 months) ]
   Participants are identified as having an objective response if they achieve either a confirmed CR or PR from first administration of study treatment to first observation of PD according to RECIST 1.1 as adjudicated by the Investigator. CR: CR defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started.
7. Confirmed Complete Response Assessed by IRC and by Investigator for Combined Therapy in Participants with MET Amplification Determined Centrally by FISH [ Time Frame: Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 42 months) ]
   Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non target) must have reduction in short axis to < 10 mm. Participants will be assessed who have confirmed CR if they achieve a confirmed CR from first administration of study treatment to first observation of PD. Participants are identified as having a confirmed CR if they achieve a confirmed CR from first administration of study treatment to first observation of PD.
8. Duration of Response Assessed by Independent Review Committee (IRC) and by Investigator for Combined Therapy in Participants with MET Amplification Determined Centrally by FISH [ Time Frame: Approximately 42 months ]
   Duration of response is the time from when the CR/PR (whichever is first) criteria are first met until PD or death due to any cause of the last tumor assessment, whichever occurs first.
9. Percentage of Participants With Disease Control Assessed by IRC and by Investigator for Combined Therapy in Participants with MET Amplification Determined Centrally by FISH [ Time Frame: Approximately 42 months ]
   Participants are identified as having objective disease control if they achieve either a confirmed CR or PR (confirmation needs to take place after the tumor assessments initially indicating CR or PR), or stable disease (SD).
10. Progression-Free Survival Assessed by the IRC and Investigator for Combined Therapy According to RECIST v1.1 in Participants with MET Amplification Determined Centrally by FISH [ Time Frame: Approximately 42 months ]
    Progression free survival is defined as the time (in months) from first administration of study treatment to the date of the first documentation of PD or death due to any cause of the last tumor assessment, whichever occurs first.
11. Overall Survival for Combined Therapy in Participants With MET Amplification Determined Centrally by FISH [ Time Frame: Approximately 42 months ]
    Overall survival is defined as the time (in months) from first administration of study treatment to the date of death.
12. Objective Response Assessed by Investigator According to RECIST v1.1 for Tepotinib Monotherapy in Participants with MET Amplification Determined Centrally by FISH [ Time Frame: Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 42 months) ]
    Participants are identified as having an objective response if they achieve either a confirmed CR or PR from first administration of study treatment to first observation of PD according to RECIST 1.1 as adjudicated by the Investigator. CR: CR defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started.
13. Confirmed Complete Response Assessed by IRC and by Investigator for Tepotinib Monotherapy in Participants With MET Amplification Determined Centrally by FISH [ Time Frame: Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 42 months) ]
    Complete Response (CR) defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non target) must have reduction in short axis to < 10 mm. Participants will be assessed who have confirmed CR if they achieve a confirmed CR from first administration of study treatment to first observation of PD. Participants are identified as having a confirmed CR if they achieve a confirmed CR from first administration of study treatment to first observation of PD.
14. Duration of Response Assessed by IRC and by Investigator for Tepotinib Monotherapy in Participants with MET Amplification Determined Centrally by FISH [ Time Frame: Approximately 42 months ]
    Duration of response is the time from when the CR/PR (whichever is first) criteria are first met until PD or death due to any cause of the last tumor assessment, whichever occurs first.
15. Percentage of Participants With Disease Control Assessed by IRC and Investigator for Tepotinib Monotherapy in Participants with MET Amplification Determined Centrally by FISH [ Time Frame: Approximately 42 months ]
    Participants are identified as having objective disease control if they achieve either a confirmed CR or PR (confirmation needs to take place after the tumor assessments initially indicating CR or PR), or stable disease (SD).
16. Progression-Free Survival Assessed by the IRC and Investigator for Tepotinib Monotherapy According to RECIST v1.1 in Participants with MET Amplification Determined Centrally by FISH [ Time Frame: Approximately 42 months ]
    Progression free survival is defined as the time (in months) from first administration of study treatment to the date of the first documentation of PD or death due to any cause of the last tumor assessment, whichever occurs first.
17. Health-Related Quality of Life as Assessed by EuroQol Five Dimension Five Level (EQ-5D-5L) Scale Score in Combination Therapy [ Time Frame: Approximately 42 months ]
18. Health-Related Quality of Life as assessed by European Organisation For Research And Treatment of Cancer Quality of Life Questionnaire Core 3D (EORTC-QLQ-C30) in Combination Therapy [ Time Frame: Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 42 months) ]
19. Health-Related Quality of Life as assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) in Combination Therapy [ Time Frame: Every 6 weeks following the Cycle 1 Day 1 visit until 9 months; every 12 weeks thereafter until disease progression, death, study withdrawal, or withdrawal of consent (each Cycle is of 21 days) (approximately 42 months) ]
20. Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Tepotinib and Osimertinib and Their Metabolities [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days) ]
21. Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Osimertinib and Their Metabolities [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days) ]
22. Time to Reach Maximum Observed Plasma Concentration (tmax) of Tepotinib and Osimertinib and Their Metabolities [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days) ]
23. Apparent Total Body Clearance (CL/f) of Tepotinib and Osimertinib and Their Metabolities [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days) ]
    The apparent total body clearance of study intervention following extravascular administration, taking into account the fraction of dose absorbed. CL/f = Dose p.o. /AUC0-infinity (AUC0-inf).
24. Apparent Volume Of Distribution (Vz/F) of Tepotinib and Osimertinib and Their Metabolities [ Time Frame: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours after tepotinib and Osimertinib administration at Day 1 of Cycle 1 and Day 15 of Cycle 1 (each Cycle is of 21 days) ]
    The apparent volume of distribution during the terminal phase following extravascular administration, based on the fraction of dose absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf)* Lambda(z).
25. Percentage of Participants With resistant Mutations of the Epidermal Growth Factor Receptor (EGFR) gene or other pathways as Assessed in Circulating Tumor Deoxyribonucleic Acid (ctDNA [ Time Frame: From Day 1 of Cycle 3 up to end of treatment (14 days after last dose) (each Cycle is for 21 days) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Locally advanced or metastatic Non-small Cell Lung Cancer (NSCLC) histology (confirmed by either histology or cytology) with documented activating Epidermal Growth Factor Receptor (EGFR) mutation
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and a minimum life expectancy of 12 weeks
• Acquired resistance on previous first-line osimertinib. Participants must meet both of the following 2 criteria:
• Radiological documentation of disease progression on first-line osimertinib
• Objective clinical benefit documented during previous osimertinib therapy, defined by either partial or complete radiological response, or durable stable disease (SD) (SD should last greater than (>) 6 months after initiation of osimertinib
• Have received only first-line osimertinib as a prior line of therapy in the non curative advanced or metastatic NSCLC setting
• MET amplification as determined by either FISH testing (central or local) on tumor tissue (TBx) or central blood-based next generation sequencing (LBx). Tumor and blood samples must be collected following progression on prior first-line osimertinib at Prescreening
• Submission of tumor tissue and blood sample obtained after progression on first-line osimertinib, is mandatory for all patients for MET amplification testing
• Submission of tumor tissue during Prescreening or Screening is mandatory for patients with tumor tissue tested by local FISH, to confirm MET amplification status. Central confirmation is not mandated prior to the start of study treatment
• Other protocol defined inclusion criteria could apply

Exclusion Criteria:

• Spinal cord compression or brain metastasis unless asymptomatic, stable or not requiring steroids for at least 2 weeks prior to start of study intervention
• Any unresolved toxicity Grade 2 or more according to National cancer institute common terminology criteria for adverse events( NCI-CTCAE) version 5, from previous anticancer therapy with the exception of alopecia
• Inadequate hematological, liver and renal function
• Impaired cardiac function
• History of interstitial lung disease(ILD) or interstitial pneumonitis including radiation pneumonitis that required steroid treatment
• Hypertension uncontrolled by standard therapies (not stabilized to < 150/90 millimeter of mercury (mmHg)
• Contraindication to the administration of osimertinib
• Other protocol defined exclusion criteria could apply.

Contacts and Locations

Locations

United States, Arizona

Yuma Regional Medical Center

Yuma, Arizona, United States, 85364

United States, California

Compassionate Care Research Group Inc - Edinger Medical Group, Inc.

Fountain Valley, California, United States, 92708

Memorial Care

Long Beach, California, United States, 90806

Ventura County Hematology Oncology Specialists

Oxnard, California, United States, 93030

Innovative Clinical Research Institute

Whittier, California, United States, 92801

United States, Connecticut

Eastern Connecticut Hematology & Oncology Associates

Norwich, Connecticut, United States, 06360

United States, Florida

Holy Cross

Fort Lauderdale, Florida, United States, 33308

Memorial Healthcare System

Hollywood, Florida, United States, 33021

Cancer Specialists of North Florida

Jacksonville, Florida, United States, 32256

Ocala Oncology

Ocala, Florida, United States, 34474

United States, Georgia

University Cancer and Blood Center

Athens, Georgia, United States, 30607

United States, Hawaii

Hawaii Cancer Care

Honolulu, Hawaii, United States, 96813

United States, Illinois

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

United States, Indiana

Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, United States, 46845

Community Health Network

Indianapolis, Indiana, United States, 46250

Beacon Health

South Bend, Indiana, United States, 46601

United States, Kentucky

Norton Cancer Institute

Louisville, Kentucky, United States, 40202

United States, Louisiana

Pontchartrain

Hammond, Louisiana, United States, 70433

United States, Maryland

Medstar Franklin Square Clinical Research Center

Baltimore, Maryland, United States, 21237

The Center for Cancer & Blood Disorders - Maryland

Bethesda, Maryland, United States, 20817

Frederick Health- James M Stockman Cancer Institute

Frederick, Maryland, United States, 21702

United States, Massachusetts

Boston Medical Center - Dept. Hematology/Oncology

Boston, Massachusetts, United States, 02118

Southcoast Center for Cancer Care

Fairhaven, Massachusetts, United States, 02719

United States, Michigan

Sparrow Hospital Herbert - Herman Cancer Center

Lansing, Michigan, United States, 48912

United States, Missouri

Central Care Cancer Center (CCCC)

Bolivar, Missouri, United States, 65613

St. Louis Cancer Care, LLP

Bridgeton, Missouri, United States, 63044

Mosaic Life Care

Saint Joseph, Missouri, United States, 64507

United States, Nevada

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States, 89169

United States, New Jersey

New Jersey Cancer Care and Blood Disorders

Belleville, New Jersey, United States, 07109

Summit Medical Group

Florham Park, New Jersey, United States, 07932

United States, New York

NYU Langone Clinical Cancer Center - NYU Langone Medical Center

New York, New York, United States, 10016

NYU Langone Clinical Cancer Center - NYU Langone Medical Cente

New York, New York, United States, 10016

Weill Cornell Medical College - Gastroenterology

New York, New York, United States, 10021

United States, North Carolina

Southeastern Medical Oncology Center

Goldsboro, North Carolina, United States, 27534

United States, Ohio

University Hospitals Seidman

Cleveland, Ohio, United States, 44106

OhioHealth

Columbus, Ohio, United States, 43214

United States, Oklahoma

Oklahoma Cancer Specialists and Research Institute

Tulsa, Oklahoma, United States, 74146

United States, Oregon

Oregon Oncology Specialists

Salem, Oregon, United States, 97301

United States, Pennsylvania

Gettysburg Cancer Center

Gettysburg, Pennsylvania, United States, 17325

United States, South Dakota

Sanford Health

Sioux Falls, South Dakota, United States, 57104

Avera Cancer Institute

Sioux Falls, South Dakota, United States, 57108

United States, Tennessee

Baptist Cancer Center

Memphis, Tennessee, United States, 38120

Tennessee Oncology

Nashville, Tennessee, United States, 37201

United States, Texas

Mary Crowley Cancer Research

Dallas, Texas, United States, 75230

University of Texas MD Anderson Cancer Center - Unit 432 Thoracic Head and Neck Medical Oncology

Houston, Texas, United States, 77030

United States, Utah

Community Cancer Trials of Utah

Ogden, Utah, United States, 84405

Utah Cancer Specialists

Salt Lake City, Utah, United States, 84106

United States, Virginia

Hematology Oncology Associates of Fredericksburg

Fredericksburg, Virginia, United States, 22408

United States, Washington

Northwest Medical Specialties

Tacoma, Washington, United States, 98405

Belgium

UZ Antwerpen - Department of Oncology

Edegem, Belgium

UZ Leuven

Gasthuisberg, Belgium

AZ Delta

Roeselare, Belgium

China

Beijing Hospital

Beijing, China

Peking Union Medical College Hospital

Beijing, China

Peking University Cancer Hospital

Beijing, China

Jilin Cancer Hospital - Oncology

Changchun, China

The First Hospital of Jilin University

Changchun, China

Hunan Cancer Hospital

Changsha, China

West China Hospital, Sichuan University

Chengdu, China

Fujian Cancer Hospital

Fuzhou, China

Guangdong General Hospital

Guangzhou, China

The First Affiliated Hospital, Zhejiang University

Hangzhou, China

Zhejiang Cancer Hospital

Hangzhou, China

Affiliated Tumor Hospital of Harbin Medical University

Harbin, China

Anhui Chest Hospital

Hefei, China

Linyi Tumor Hospital

Linyi, China

Jiangsu Province Hospital

Nanjing, China

Shanghai Cancer Hospital, Fudan University

Shanghai, China

Shanghai Chest Hospital

Shanghai, China

Liaoning Cancer Hospital & Institute

Shenyang, China

The Affiliated Cancer Hospital of Xinjiang Medical university

Urumqi, China

Hubei Cancer Hospital

Wuhan, China

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, China

France

Centre Francois Baclesse - Service d'Oncologie Medicale

Caen Cedex 05, France

Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie

Creteil Cedex, France

CHU Limoges - Hôpital Dupuytren - Unite d'Oncologie Thoracique et Cutanée

Limoges, France

Centre Léon Bérard

Lyon, France

Hopital Albert Calmette - CHU Lille - service de pneumologie et immuno allergologie

Nord, France

Hospital Cochin Service, Service de Pneumologie et Mucoviscidose

Paris cedex 14, France

Hopital Tenon - service pneumologie

Paris, France

Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Maison du Ha

Pessac, France

CHU de Toulouse - Hôpital Larrey - Service de Pneumologie et Oncologie Pneumologique

Toulouse, France

Germany

Universitaetsklinikum Carl Gustav Carus TU Dresden

Dresden, Germany

Asklepios Fachkliniken Muenchen-Gauting - Abteilung internistische Onkologie

Gauting, Germany

Universitaetsklinikum Giessen und Marburg GmbH Standort Giessen

Giessen, Germany

Universitaetsmedizin Goettingen

Göttingen, Germany

Evangelisches Krankenhaus Hamm gGmbH

Hamm, Germany

Evangelisches Krankenhaus Hamm GmbH

Hamm, Germany

Thoraxklinik-Heidelberg gGmbH

Heidelberg, Germany

Staedtisches Krankenhaus Kiel

Kiel, Germany

Universitaetsklinikum Koeln - Innere Medizin I, Onkologie, Haematologie

Koeln, Germany

POIS Leipzig GbR

Leipzig, Germany

Universitaetsklinikum Schleswig-Holstein - Campus Luebeck

Luebeck, Germany

Pius-Hospital Oldenburg - Klinik f. Haematologie und Onkologie

Oldenburg, Germany

Missionsärztliche Klinik

Wuerzburg, Germany

Hong Kong

Queen Elizabeth Hospital - Department of Medicine

Hong Kong, Hong Kong

The University of Hong Kong

Hong Kong, Hong Kong

The Chinese University of Hong Kong - Emergency Medicine

Shatin, Hong Kong

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Oncologia Medica

Lazio, Italy

IEO Istituto Europeo di Oncologia

Milano, Italy

Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo) - U.O Oncologia Medica

Monza, Italy

Ospedale Monaldi

Napoli, Italy

IOV - Istituto Oncologico Veneto IRCCS - Oncologia Medica 2

Padova, Italy

AO Ospedali Riuniti Cervello - Presidio Villa Sofia - U.O.S. di Neuroimmunologia

Palermo, Italy

Azienda Ospedaliero Universitaria Pisana - U.O. Pneumologia II

Pisa, Italy

Istituto Nazionale Tumori Regina Elena IRCCS - S.C. Oncologia Medica B

Roma, Italy

Istituto Clinico Humanitas

Rozzano, Italy

Azienda Socio Sanitaria Territoriale Sette Laghi (Presidio Ospedale di Circolo e Fondazione Macchi) - Oncologia Medica

Varese, Italy

Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) - U.O.C. Oncologia

Verona, Italy

Japan

Hamamatsu University School of Medicine, University Hospital - Dept of Respiratory Medicine

Hamamatsu-shi, Japan

Saitama Cancer Center

Kitaadachi-gun, Japan

Kurume University Hospital

Kurume-shi, Japan

Nagoya University Hospital - Dept of Respiratory Medicine

Nagoya-shi, Japan

Niigata Cancer Center Hospital - Dept of Internal Medicine

Niigata-shi, Japan

Hyogo College of Medicine Hospital - Dept of Respiratory Medicine

Nishinomiya-shi, Japan

Okayama University Hospital - Dept of Respiratory Medicine/Allergy

Okayama-shi, Japan

Osaka City General Hospital

Osaka-shi, Japan

Kindai University Hospital

Osakasayama-shi, Japan

NHO Yamaguchi - Ube Medical Center

Ube-shi, Japan

Kanagawa Cancer Center - Dept of Respiratory Medicine

Yokohama-shi, Japan

Korea, Republic of

National Cancer Center

Goyang-si, Korea, Republic of

Chonnam National University Hwasun Hospital

Hwasun-gun, Korea, Republic of

Seoul National University Bundang Hospital

Seongnam-si, Korea, Republic of

Asan Medical Center

Seoul, Korea, Republic of

Korea University Anam Hospital

Seoul, Korea, Republic of

Samsung Medical Center

Seoul, Korea, Republic of

Seoul National University Hospital

Seoul, Korea, Republic of

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, Korea, Republic of

Ulsan University Hospital

Ulsan, Korea, Republic of

Malaysia

Pantai Hospital Kuala Lumpur

Kuala Lumpur, Malaysia

University Malaya Medical Centre

Kuala Lumpur, Malaysia

Hospital Tengku Ampuan Afzan

Kuantan, Malaysia

Hospital Umum Sarawak

Kuching, Malaysia

Sunway Medical Centre

Petaling Jaya, Selangor, Malaysia

Hospital Pulau Pinang - Clinic Respiratory

Pulau Pinang, Malaysia

Beacon International Specialist Centre Sdn Bhd

Selangor, Malaysia

Netherlands

The Netherlands Cancer Institute

Amsterdam, Netherlands

Universitair Medisch Centrum Groningen - Department of Internal Medicine

Groningen, Netherlands

Maastricht University Medical Center - Dept of Medical Oncology

Maastricht, Netherlands

Russian Federation

SBHI "Krasnoyarsk Regional Oncology Dispensary n.a. A.I. Kryzhanovsky"

Krasnoyarsk, Russian Federation

"VitaMed" LLC

Moscow, Russian Federation

LLC "Tonus"

Nizniy Novgorod, Russian Federation

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, Russian Federation

LLC "ClinicaUZI4D"

Pyatigorsk, Russian Federation

FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"

Saint-Petersburg, Russian Federation

Pavlov First Saint Petersburg State Medical University - Research Institute of Pulmunology

St. Petersburg, Russian Federation

Singapore

Icon Cancer Centre

Connexion, Singapore

National Cancer Centre - Medical Oncology Pharmacy

Singapore, Singapore

Tan Tock Seng Hospital - CTRU/OCS, Research

Singapore, Singapore

Spain

ICO Badalona - Hospital Germans Trias i Pujol - Servicio de Oncologia Medica

Badalona, Spain

Hospital del Mar - Servicio de Oncologia

Barcelona, Spain

Hospital Universitari Dexeus - Servicio de Oncologia Medica

Barcelona, Spain

Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica

Barcelona, Spain

Hospital Universitari Vall d'Hebron - Dept of Oncology

Barcelona, Spain

ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia

L'Hospitalet de Llobregat, Spain

Hospital Universitario Materno-Infantil de Canarias - Servicio de Oncologia

Las Palmas de Gran Canaria, Spain

Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia

Madrid, Spain

Hospital Regional Universitario de Malaga

Málaga, Spain

Hospital Universitari Son Espases - Servicio de Oncologia Medica

Palma, Spain

Hospital Universitario Quiron Madrid - Unidad Integral de Oncologia

Pozuelo de Alarcon, Spain

Hospital Universitario Virgen Macarena - Servicio de Oncologia

Sevilla, Spain

Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica

Valencia, Spain

Taiwan

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung, Taiwan

China Medical University Hospital

Taichung, Taiwan

Taichung Veterans General Hospital

Taichung, Taiwan

Chi Mei Medical Center, Liou Ying

Tainan, Taiwan

National Taiwan University Hospital

Taipei, Taiwan

Taipei Veterans General Hospital

Taipei, Taiwan

Tri-Service General Hospital

Taipei, Taiwan

Thailand

Siriraj Hospital

Bangkoknoi, Thailand

Songklanagarind Hospital

Hat Yai, Thailand

Maharaj Nakorn Chiang Mai Hospital

Muang, Thailand

King Chulalongkorn Memorial Hospital

Pathumwan, Thailand

Vietnam

Bach Mai Hospital

Hanoi, Vietnam

K Hospital

Hanoi, Vietnam

National Lungs Hospital

Hanoi, Vietnam

Cho Ray Hospital

Ho Chi Minh City, Vietnam

HCMC Oncology Hospital

Ho Chi Minh city, Vietnam

Pham Ngoc Thach Hospital

Ho Chi Minh City, Vietnam

Sponsors and Collaborators

EMD Serono Research & Development Institute, Inc.

Merck KGaA, Darmstadt, Germany

Investigators

• Study Director: Medical Responsible; Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

More Information

Additional Information:

Trial Awareness and Transparency website 

Publications:

F Smit E, Dooms C, Raskin J, Nadal E, Tho LM, Le X, Mazieres J, S Hin H, Morise M, W Zhu V, Tan D, H Holmberg K, Ellers-Lenz B, Adrian S, Brutlach S, Schumacher KM, Karachaliou N, Wu YL. INSIGHT 2: a phase II study of tepotinib plus osimertinib in MET-amplified NSCLC and first-line osimertinib resistance. Future Oncol. 2022 Mar;18(9):1039-1054. doi: 10.2217/fon-2021-1406. Epub 2021 Dec 17.

• Responsible Party: EMD Serono Research & Development Institute, Inc.
• ClinicalTrials.gov Identifier: NCT03940703
• Other Study ID Numbers: MS200095_0031; 2019-001538-33 ( EudraCT Number )
• First Posted: May 7, 2019
• Last Update Posted: November 30, 2023
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients 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 https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• 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
• 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.
• URL: http://bit.ly/IPD21

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):

Tepotinib; Osimertinib; Non-Small Cell Lung Cancer; INSIGHT 2; MET amplified

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Osimertinib; Tepotinib; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents