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. )

Tracking Information

• First Submitted Date: May 6, 2019
• First Posted Date: May 7, 2019
• Last Update Posted Date: November 30, 2023
• Actual Study Start Date: September 19, 2019
• Actual Primary Completion Date: May 11, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 3, 2020)

• 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) ]
• 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.

Original Primary Outcome Measures (submitted: May 6, 2019)

• Safety run-in: Number of Participants Experiencing Dose Limiting Toxicities (DLT) 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) ]
• Objective response determined according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as per Independent Review Committee (IRC) [ 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 21.7 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.

Current Secondary Outcome Measures (submitted: August 14, 2020)

• 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.
• 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.
• 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 ]
• 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 ]
• 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.
• 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.
• 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.
• 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.
• 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).
• 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.
• 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.
• 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.
• 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.
• 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.
• 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).
• 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.
• 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 ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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) ]
• 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).
• 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).
• 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) ]

Original Secondary Outcome Measures (submitted: May 6, 2019)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) 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 (approximately 10.5 months) ]
• 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 (approximately 10.5 months) ]
• 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 (approximately 10.5 months) ]
  Percentage of participants with abnormalities in Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, body temperature as a part of vital signs; electrocardiogram (ECG) wave and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) will be assessed.
• Objective Response According to RECIST 1.1 assessed by Investigator [ 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 21.7 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.
• Confirmed Complete Response assessed by Independent Review Committee and by Investigator [ 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 21.7 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.
• Duration of Response assessed by Independent Review Committee and by Investigator [ Time Frame: Approximately 21.7 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.
• Percentage of Participants With Disease Control as assessed by Independent Review Committee and by Investigator [ Time Frame: Approximately 21.7 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).
• Progression-Free Survival Based on Tumor Assessment by the Independent Review Committee and Investigator According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria [ Time Frame: Approximately 21.7 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.
• Overall Survival [ Time Frame: Approximately 21.7 months ]
  Overall survival is defined as the time (in months) from first administration of study treatment to the date of death.
• Health-Related Quality of Life as Assessed by EuroQol Five Dimension Five Level (EQ-5D-5L) Scale Score [ Time Frame: Approximately 21.7 months ]
• 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) [ 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 21.7 months) ]
• Health-Related Quality of Life as assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) [ 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 21.7 months) ]
• Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of Tepotinib and Osimertinib [ 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) ]
• Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Osimertinib [ 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) ]
• Time to Reach Maximum Observed Plasma Concentration (tmax) of Tepotinib and Osimertinib [ 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) ]
• Apparent Total Body Clearance (CL/f) of Tepotinib and Osimertinib [ 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).
• Apparent Volume Of Distribution (Vz/F) of Tepotinib and Osimertinib [ 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).
• Percentage of Participants With Epidermal Growth Factor Receptor (EGFR) Mutation [ Time Frame: From Day 1 of Cycle 3 up to end of treatment (14 days after last dose) (each Cycle is for 21 days) (approximately 7.5 months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2)
• 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)
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer

Intervention

• 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®

Study Arms

• 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.
  Interventions:

  • Drug: Tepotinib
  • Drug: Osimertinib
• 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.
  Intervention: Drug: Tepotinib

• 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 3, 2020): 120
• Original Estimated Enrollment (submitted: May 6, 2019): 90
• Estimated Study Completion Date: May 27, 2024
• Actual Primary Completion Date: May 11, 2023 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, China, France, Germany, Hong Kong, Italy, Japan, Korea, Republic of, Malaysia, Netherlands, Russian Federation, Singapore, Spain, Taiwan, Thailand, United States, Vietnam

Administrative Information

• NCT Number: NCT03940703
• Other Study ID Numbers: MS200095_0031; 2019-001538-33 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

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
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: 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

• Current Responsible Party: EMD Serono ( EMD Serono Research & Development Institute, Inc. )
• Original Responsible Party: Same as current
• Current Study Sponsor: EMD Serono Research & Development Institute, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck KGaA, Darmstadt, Germany

Investigators

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

• PRS Account: EMD Serono
• Verification Date: November 2023