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Non-small Cell Lung CancerPhase 1/2NCT01982955

Tepotinib With Gefitinib in Participants With Locally Advanced or Metastatic NSCLC (INSIGHT)

A Phase 1/2 study testing Tepotinib, Gefitinib and Pemetrexed in people with Non-small Cell Lung Cancer, run by Merck KGaA, Darmstadt, Germany at 44 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a multi-center, open-label, randomized, Phase 1b/2 study to determine the recommended phase 2 dose (RP2D) and to evaluate the efficacy in terms of progression free survival (PFS) of Tepotinib when used in combination with gefitinib in partcipants with T790M negative, MET positive locally advanced or metastatic… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Tepotinib, Gefitinib and Pemetrexed
Could I receive a placebo?
No, everyone receives an active treatment
How many people
88 participants
Where
44 sitesin 7 countries
Study dates
23 Dec 2013to 14 Oct 2021
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically or cytologically confirmed advanced non-small cell lung cancer (NSCLC), regardless of histology subtype, which failed on gefitinib for reasons other than toxicity or compliance;
  • Availability of a fresh or archived pre treatment tumor biopsy (excluding fine needle aspiration and cytology samples). For participants who have had at least 1 prior anticancer treatment, a biopsy obtained between failure of the most recent anticancer treatment and enrolment is mandatory;
  • Mesenchymal-epithelial transition diagnostic-positive (status) (MET+ status), as determined by the central laboratory
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  • Other protocol defined inclusion criteria could apply.
  • Phase II
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  • Locally advanced or metastatic NSCLC other than predominantly squamous histology (confirmed by either histology or cytology);
  • Activating mutation of the epidermal growth factor (EGFR) receptor (documented, or as determined by the central laboratory)
  • Acquired resistance on first-line EGFR-Tyrosine Kinase Inhibitors (EGFR-TKI) therapy including gefitinib, erlotinib, icotinib, or afatinib
  • EGFR T790M status after acquired resistance to first line EGFR-TKI therapy including gefitinib, erlotinib, icotinib, or afatinib treatment (as determined by the central laboratory, using a validated PCR test);
  • T790M negative status for the randomized part
  • T790M positive status for the single-arm cohort (mainland China sites only)
  • Availability of a fresh or archived tumor tissue (excluding fine needle aspiration and cytology samples) obtained between documentation of acquired resistance to gefitinib, erlotinib, icotinib, or afatinib and enrollment is mandatory
  • MET+ status, as determined by the central laboratory i.e. c-Met overexpression as determined by IHC (i.e., IHC 2+ or IHC 3+) and/or c-Met amplification and/or increased c-Met gene copy number (GCN), both determined by ISH;
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Other protocol defined inclusion criteria could apply

Who cannot join

  • Estimated life expectancy less than (<) 3 months
  • Inadequate bone marrow, liver or renal functions
  • Prior chemotherapy, biological therapy, radiation therapy, or other investigational anticancer therapy (not including palliative radiotherapy at focal sites) within 21 days prior to the first dose of study treatment (Phase 1b only)
  • Prior systemic anticancer treatment with chemotherapy or other agents targeting the EGFR pathway excluding gefitinib, erlotinib, icotinib, and afatinib for advanced NSCLC (one course of chemotherapy regimen for [neo] adjuvant purpose, or one course of chemoradiation for Stage IIIa disease is allowed) (Phase 2 only)
  • Other protocol defined exclusion criteria could apply.

Trial locations and contacts

44 sites in 7 countries.

44 sites in 7 countries

China13 sites

  • Beijing Cancer Hospital

    Beijing

  • Beijing Chest Hospital

    Beijing

  • Peking Union Medical College Hospital

    Beijing

  • Jilin Cancer Hospital

    Changchun

  • Jilin University

    Changchun

  • Fuzhou General Hospital

    Fuzhou

  • Guangdong Provincial People's Hospital

    Guangzhou

  • Sir Run Run Shaw Hospital Cardiology

    Hangzhou

  • The First Affiliated Hospital of College of Medicine

    Hangzhou

  • Shanghai Chest Hospital

    Shanghai

  • Tongji Hospital

    Wuhan

  • Fourth Military Medical University

    Xi'an

  • Zhejiang Cancer Hospital

    Zhejiang

Other trials in China

South Korea13 sites

  • Chungbuk National University Hospital

    Cheongju-si

  • Kyungpook National University Hospital

    Daegu

  • Chonnam National University Hwasun Hospital

    Hwasun

  • CHA Bundang Medical Center, CHA University

    Seongnam-si

  • Seoul National University Bundang Hospital

    Seongnam-si

  • Severance Hospital Yonsei University Health System

    Seongnam-si

  • Asan medical Centre

    Seoul

  • Gangnam Severance Hospital Yonsei University

    Seoul

  • Korea University Anam Hospital

    Seoul

  • Samsung Medical Center

    Seoul

  • Seoul National Universtiy Hospital

    Seoul

  • The Catholic University of Korea St Mary s Hospital

    Seoul

  • The Catholic University of Korea St. Vincent's Hospital

    Suwon

Other trials in South Korea

Taiwan7 sites

  • Chang Gung Memorial Hospital-Kaohsiung

    Kaohsiung City

  • China Medical University Hospital

    Taichung

  • Taichung Veterans General Hospital

    Taichung

  • National Taiwan University Hospital

    Taipei

  • Taipei Veterans General Hospital

    Taipei

  • Tri-Service General Hospital

    Taipei

  • Chang Gung Memorial Hospital Linkou

    Taoyuan

Other trials in Taiwan

Spain4 sites

  • Hospital Universitari Vall d'Hebron

    Barcelona

  • Hospital General Universitario Gregorio Marañon

    Madrid

  • Hospital Clinico Universitario

    Valencia

  • Hospital Alvaro Cunqueiro

    Vigo

Other trials in Spain

Singapore3 sites

  • National Cancer Center

    Singapore

  • National University Hospital

    Singapore

  • Raffles Hospital

    Singapore

Other trials in Singapore

Italy2 sites

  • Azienda Ospedaliero Universitaria Mater Domini-Campus Universitario

    Catanzaro

  • IEO Istituto Europeo di Oncologia

    Milan

Other trials in Italy

Malaysia2 sites

  • University Malaya Medical Centre

    Kuala Lumpur

  • Beacon International Specialist Centre Sdn Bhd

    Petaling Jaya

Other trials in Malaysia

About this study

Official title: A Phase Ib/II Multicenter, Randomized, Open Label Trial to Compare Tepotinib (MSC2156119J) Combined With Gefitinib Versus Chemotherapy as Second-Line Treatment in Subjects With MET Positive, Locally Advanced or Metastatic NSCLC Harboring EGFR Mutation and Having Acquired Resistance to Prior EGFR-TKI Therapy (INSIGHT)

This is a multi-center, open-label, randomized, Phase 1b/2 study to determine the recommended phase 2 dose (RP2D) and to evaluate the efficacy in terms of progression free survival (PFS) of Tepotinib when used in combination with gefitinib in partcipants with T790M negative, MET positive locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation and having acquired resistance to Prior EGFR-Tyrosine Kinase Inhibitor (EGFR-TKI) Therapy. This study has 2:1 randomization (Tepotinib/Gefitinib arm versus Chemotherapy arm).

Being tested
Tepotinib, Gefitinib, Pemetrexed, Cisplatin, Carboplatin
Keywords
MSC2156119J, Gefitinib, Pemetrexed, Cisplatin, MET positive, Tepotinib, Carboplatin, INSIGHT
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TepotinibDrug

    Tepotinib was administered at a dose range of 300 or 500 milligram (mg) (Phase 1b) and the recommended phase II dose (RP2D) determined in the Phase 1b in Phase II orally once daily over a 21-day cycle until progressive disease, intolerable toxicity, participants withdrawal from treatment. RP2D was determined as per safety monitoring committee (SMC) discretion.

  • GefitinibDrug

    Gefitinib was administered at a dose of 250 mg orally as once daily over a 21-day cycle until progressive disease, intolerable toxicity, participants withdrawal from treatment.

  • PemetrexedDrug

    Pemetrexed was administered at a dose of 500 milligram per square meter (mg/m^2) as intravenous infusion over 10 minutes on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity, participants withdrawal from treatment or up to 6 cycles if pemetrexed maintenance is not considered.

  • CisplatinDrug

    Cisplatin was administered at a dose of 75 mg/m^2 as intravenous infusion over 2 hours on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity, participants withdrawal from treatment or up to 6 cycles if pemetrexed maintenance is not considered.

  • CarboplatinDrug

    Carboplatin was administered intravenously on Day 1 of each 21-day cycle at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator until progressive disease, intolerable toxicity, participants withdrawal from treatment or up to 6 cycles if pemetrexed maintenance is not considered.

Study groups in NCT01982955
Study groupRoleWhat they receive
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mgExperimentalParticipants received Tepotinib 300 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Receives: Drug: Tepotinib; Drug: Gefitinib
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mgExperimentalParticipants received Tepotinib 500 milligram (mg) along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Receives: Drug: Tepotinib; Drug: Gefitinib
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 negative)ExperimentalParticipants randomized to receive Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Receives: Drug: Tepotinib; Drug: Gefitinib
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 negative)ExperimentalParticipants randomized to receive 500 milligram per square meter (mg/m^2) of Pemetrexed as intravenous infusion over 10 minutes in combination with Cisplatin (75 mg/m2 as an intravenous infusion over 2 hours) or Carboplatin (intravenously at a dose of area under curve (AUC) 5 or AUC6 at the discretion of the Investigator) on Day 1 of each 21-day cycle until progressive disease, intolerable toxicity or withdrawal from treatment or up to 6 cycles if or 4 cycles followed by Pemetrexed maintenance monotherapy.
Receives: Drug: Pemetrexed; Drug: Cisplatin; Drug: Carboplatin
Phase 2: Single-arm Cohort (MET+ T790M positive)ExperimentalParticipants with MET+ T790M positive Non-small Cell Lung Cancer (NSCLC) received a Tepotinib recommended Phase 2 dose 500 mg once daily along with 250 mg Gefitinib tablets orally once daily over a 21-day treatment cycle until progressive disease, intolerable toxicity or withdrawal from treatment.
Receives: Drug: Tepotinib; Drug: Gefitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b: Number of Participants Experiencing at Least One Dose Limiting Toxicity (DLT)

    Dose limiting toxicity (DLT) using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 was defined as toxicities at any dose level and judged to be related to the study treatment by investigator and/or the sponsor. DLTs included Grade 4 neutropenia for more than 7 days; Grade greater than or equal to (>=) 3 febrile neutropenia for more than 1 day; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with non-traumatic bleeding; Grade >= 3 uncontrolled nausea/vomiting and/or diarrhea despite adequate and optimal treatment and Grade >= 3 any non-hematological adverse event (AE), except the aforementioned gastrointestinal events and alopecia. Number of participants who experienced DLT during Phase 1b were reported.

    Measured: Day 1 to Day 21 of Cycle 1 (each cycle is 21 days)

  2. Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

    An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs and serious TEAEs were reported.

    Measured: Up to 175 weeks

  3. Phase 2 (Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by the Investigator

    Progression-free survival (assessed by the Investigator) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease (PD) by the investigator or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter (mm). PFS was measured using Kaplan-Meier (KM) estimates.

    Measured: Up to 328 weeks

Secondary outcomes (41)

  1. Phase 1b: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time AUC (0-t) of Tepotinib, Its Metabolites and Gefitinib

    Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule.

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

  2. Phase 1b: Area Under the Plasma Concentration-Time Curve Within 1 Dosing Interval (AUC 0-tau) of Tepotinib, Its Metabolites and Gefitinib

    AUC (0-tau) is the area under the plasma concentration time curve within 1 dosing interval.

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

  3. Phase 1b: Maximum Observed Plasma Concentration (Cmax) of Tepotinib, Its Metabolites and Gefitinib

    Cmax is the maximum observed plasma concentration obtained directly from the concentration versus time curve.

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

  4. Phase 1b: Average Observed Plasma Concentration (Cavg) of Tepotinib, Its Metabolites and Gefitinib

    Cavg is the average plasma concentration within 1 dosing interval obtained directly from the concentration versus time curve.

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 15 of Cycle 1 (each Cycle is 21 days)

  5. Phase 1b: Minimum Observed Plasma Concentration (Cmin) of Tepotinib, Its Metabolites and Gefitinib

    Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve.

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 15 of Cycle 1 (each Cycle is 21 days)

  6. Phase 1b: Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib, Its Metabolites and Gefitinib

    Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve.

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

  7. Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC 0-infinity) of Tepotinib, Its Metabolites and Gefitinib

    The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

  8. Phase 1b: Apparent Total Body Clearance From Plasma (CL/F) of Tepotinib and Gefitinib

    The CL/f is a measure of the rate at which it was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed. The CL/F from plasma was calculated using the formula: Dose divided by area under the concentration time curve from time zero to infinity (AUC0-inf).

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 15 of Cycle 1 (each Cycle is 21 days)

  9. Phase 1b: Apparent Volume of Distribution (Vz/F) During the Terminal Phase of Tepotinib, Its Metabolites and Gefitinib

    The Vz/f was defined as the theoretical volume in which the total amount of required to uniformly distribute to produce the desired plasma concentration. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction 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) multiply Lambda(z).

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

  10. Phase 1b: Apparent Volume of Distribution During the Steady State (Vss/F) of Tepotinib, Its Metabolites and Gefitinib

    Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss/f after oral dose was influenced by the fraction absorbed.

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

  11. Phase 1b: Apparent Terminal Elimination Rate Constant Lambda(z) of Tepotinib, Its Metabolites and Gefitinib

    Lambda(z) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

  12. Phase 1b: Apparent Terminal Half-Life (t1/2) of Tepotinib, Its Metabolites and Gefitinib

    Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination.

    Measured: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

  13. Phase 1b: Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

    Objective response (OR) was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to local radiological assessments from randomization/the first administration of the study treatment to the first observation of disease progression (PD). 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 and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: Up to 328 weeks

  14. Phase 1b: Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

    Disease control defined as CR, PR, or stable disease(SD) as the best overall response according to local radiological assessments from the date of randomization/the first administration of the study treatment to the first observation of PD. CR: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:at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD: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 and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5mm. SD:as any cases that do not qualify for either PR or PD at minimum interval of 42 days after randomization/start of study treatment

    Measured: Up to 328 weeks

  15. Phase 1b: Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Serious TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03

    An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE was defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Treatment-related AE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator.

    Measured: Up to 175 weeks

  16. Phase 1b: Number of Participants With Grade 3/4 Treatment-Emergent Adverse Events (TEAEs) and Grade 3/4 Treatment-Related TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03

    An adverse event (AE) was defined as any untoward medical occurrence in participant which does not necessarily have casual relationship with treatment was any unfavorable and unintended sign(including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. Term TEAE was defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Treatment-related TEAE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator. As per NCI-CTCAE, Grade 3 is Severe, Grade 4 is Life-threatening and Grade 5 or Death. Number of participants with Grade 3/4 TEAEs and Grade 3/4 treatment-related TEAEs were reported.

    Measured: Up to 175 weeks

  17. Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Permanent Treatment Discontinuation

    An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Number of participants with TEAEs leading to permanent treatment discontinuation were reported.

    Measured: Up to 175 weeks

  18. Phase 1b: Number of Participants With Death and Reasons

    Number of participants with death due to progressive disease (PD), adverse event (AE) related to study treatment, AE not related to study treatment were reported. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. 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 and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. Number of participants with deaths due to PD, AE related to study treatment, AE not related to study treatment were reported.

    Measured: Up to 175 weeks

  19. Phase 1b: Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI-CTCAE Version 4.03 Reported as Treatment-Emergent Adverse Events (TEAEs)

    The laboratory measurements included hematology and coagulation, biochemistry and urinalysis.

    Measured: Up to 175 weeks

  20. Phase 1b: Number of Participants With Clinically Significant Abnormalities in Vital Signs

    Vital signs assessment included blood pressure, heart rate, respiratory rate and body temperature. Number of Participants with any clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator.

    Measured: Up to 175 weeks

  21. Phase 1b: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiograms (ECG) Findings

    ECG parameters included heart rhythm, pulse rate intervals, QRS, QT intervals, RR intervals and corrected QT(QTc) intervals. Clinical significance was determined by the investigator. Number of participants with clinically significant abnormalities in 12-lead ECG were reported.

    Measured: Up to 175 weeks

  22. Phase 1b: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2

    ECOG PS score is widely used by doctors and researchers to assess how a participants' disease is progressing, and is used to assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. The score ranges from Grade 0 to Grade 5, where Grade 0 = Fully active, able to carry on all pre-disease performance without restriction, Grade 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade 2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade 5 = Death. Number of participants with ECOG performance status score of 2 or higher than 2 were reported.

    Measured: Up to 175 weeks

  23. Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-Related TEAEs and Treatment-Related Serious TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03

    An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs was defined as AEs that started or worsened in severity within the first dosing day of study treatment after the last dose of study treatment. TEAEs include both Serious TEAEs and non-serious TEAEs Treatment related AE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator.

    Measured: Up to 328 weeks

  24. Phase 2: Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent Adverse Events (TEAEs) and >= Grade 3 Treatment-Related TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03

    An adverse event (AE) was defined as any untoward medical occurrence in participant which does not necessarily have casual relationship with treatment was any unfavorable and unintended sign(including abnormal laboratory finding), symptom/disease temporally associated with use of medicinal product, whether/not considered related to medicinal product. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Treatment-related AE was defined as having a "Possible" or "Related" relationship to study treatment, as assessed by the Investigator. As per NCI-CTCAE, Grade 3 is Severe, Grade 4 is Life-threatening and Grade 5 or Death. Number of Participants With >= Grade 3 TEAEs and >= Grade 3 treatment-related TEAEs were reported.

    Measured: Up to 328 weeks

  25. Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Permanent Treatment Discontinuation

    An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Number of participants with TEAEs leading to permanent treatment discontinuation were reported.

    Measured: Up to 328 weeks

  26. Phase 2: Number of Participants With Death and Reasons

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. 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 and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. Number of participants with deaths due to progression disease (PD), AE related to study treatment, unknown reason was reported.

    Measured: Up to 328 weeks

  27. Phase 2: Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI-CTCAE Version 4.03 Reported as Treatment-Emergent Adverse Events (TEAEs)

    The laboratory measurements included hematology and coagulation, biochemistry and urinalysis.

    Measured: Up to 328 weeks

  28. Phase 2: Number of Participants With Clinically Significant Abnormalities in Vital Signs

    Vital signs assessment included blood pressure, heart rate, respiratory rate and body temperature. Number of Participants with any clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator.

    Measured: Up to 328 weeks

  29. Phase 2: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiograms (ECG) Findings

    ECG parameters included heart rhythm, pulse rate intervals, QRS, QT intervals, RR intervals and corrected QT(QTc) intervals. Clinical significance was determined by the investigator. Number of participants with clinically significant abnormalities in 12-lead ECG were reported.

    Measured: Up to 328 weeks

  30. Phase 2: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2

    ECOG PS score is widely used by doctors and researchers to assess how a participants' disease is progressing, and is used to assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. The score ranges from Grade 0 to Grade 5, where Grade 0 = Fully active, able to carry on all pre-disease performance without restriction, Grade 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade 2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade 5 = Death. Number of participants with ECOG performance status score of 2 or higher than 2 were reported.

    Measured: Up to 328 weeks

  31. Phase 2 (Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Independent Review Committee (IRC)

    Progression-free survival (assessed by Independent Review Committee) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease (PD) by the IRC or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. PFS was measured using Kaplan-Meier (KM) estimates.

    Measured: Up to 328 weeks

  32. Phase 2: (Randomized Part Only): Overall Survival (OS) Time

    Overall survival time was measured as time in months between the date of randomization and the date of death.

    Measured: Up to 328 weeks

  33. Phase 2 (Randomized Part Only): Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

    Objective response (OR) was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to local radiological assessments from randomization/the first administration of the study treatment to the first observation of disease progression (PD). 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 and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: Up to 328 weeks

  34. Phase 2 (Randomized Part Only): Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

    Disease control defined as CR, PR, or stable disease(SD) as the best overall response according to local radiological assessments from the date of randomization/the first administration of the study treatment to the first observation of PD. CR: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:at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD: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 and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5mm. SD:as any cases that do not qualify for either PR/PD at minimum interval of 42 days after randomization/start of study treatment.

    Measured: Up to 328 weeks

  35. Phase 2 (Non-Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Investigator

    Progression-free survival (assessed by Investigator) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease by the Investigator or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. PFS was measured using Kaplan-Meier (KM) estimates.

    Measured: Up to 328 weeks

  36. Phase 2 (Non-Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Independent Review Committee (IRC)

    Progression-free survival (assessed by Independent Review Committee) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease by the IRC or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. PFS was measured using Kaplan-Meier (KM) estimates.

    Measured: Up to 328 weeks

  37. Phase 2: (Non-Randomized Part Only): Overall Survival (OS) Time

    Overall survival time was measured as time in months between the date of randomization and the date of death.

    Measured: Up to 328 weeks

  38. Phase 2 (Non-Randomized Part Only): Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

    Objective response (OR) was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to local radiological assessments from randomization/the first administration of the study treatment to the first observation of disease progression (PD). 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 and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: Up to 328 weeks

  39. Phase 2 (Non-Randomized Part Only): Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

    Disease control defined as CR, PR, or stable disease(SD) as the best overall response according to local radiological assessments from the date of randomization/the first administration of the study treatment to the first observation of PD. CR: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:at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD: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 and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5mm. SD:as any cases that do not qualify for either PR/PD at minimum interval of 42 days after randomization/start of study treatment.

    Measured: Up to 328 weeks

  40. Phase 2: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score at End of Treatment (EOT)

    EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.

    Measured: Baseline and EOT (up to 110 weeks)

  41. Phase 2: Time-to-Symptom Progression (TTSP)

    TTSP was measured from randomization to symptomatic progression by lung cancer symptom scale (LCSS) used to measure symptom changes relevant to quality of life (QoL).It consisted of 9 items focused on cancer symptoms (loss of appetite, fatigue, cough, shortness of breath, blood in sputum, pain, symptoms of cancer, illness affecting normal activity, QoL).For each symptom score distance from left boundary to point where participant has marked line was measured in millimeters (mm).Total scale length was 100 mm. Symptomatic progression was defined as increase/worsening of average symptomatic burden index (ASBI) (mean of 6 major lung cancer specific symptom scores);Worsening defined as 10% increase of scale breadth from baseline. Score 0 indicate no/minimum symptoms;100 indicates maximum level of symptoms.

    Measured: Up to 328 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2013 (estimated)
  2. Study start23 Dec 2013
  3. Primary completion12 Dec 2017
  4. Study completion14 Oct 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
88 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01982955
Sponsor's protocol ID
EMR 200095-006
Other IDs
2016-001604-28, 2016
Status last verified
Oct 2022
First submitted
29 Oct 2013
Last updated
8 Nov 2022
Data monitoring committee
Yes

Publications

  • Wu YL, Cheng Y, Zhou J, Lu S, Zhang Y, Zhao J, Kim DW, Soo RA, Kim SW, Pan H, Chen YM, Chian CF, Liu X, Tan DSW, Bruns R, Straub J, Johne A, Scheele J, Park K, Yang JC; INSIGHT Investigators. Tepotinib plus gefitinib in patients with EGFR-mutant non-small-cell lung cancer with MET overexpression or MET amplification and acquired resistance to previous EGFR inhibitor (INSIGHT study): an open-label, phase 1b/2, multicentre, randomised trial. Lancet Respir Med. 2020 Nov;8(11):1132-1143. doi: 10.1016/S2213-2600(20)30154-5. Epub 2020 May 29.

    PubMed 32479794

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Tepotinib, Gefitinib and Pemetrexed in people with Non-small Cell Lung Cancer, run by Merck KGaA, Darmstadt, Germany at 44 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in China, South Korea, Taiwan, Spain, Singapore and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b: Number of Participants Experiencing at Least One Dose Limiting Toxicity (DLT) (time frame: Day 1 to Day 21 of Cycle 1 (each cycle is 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01982955, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.

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