A Study of Tepotinib Plus Osimertinib in Osimertinib Relapsed MET Amplified NSCLC (INSIGHT 2)
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03940703
- Brief Summary
This study was to 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 available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 140
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Tepotinib Mono-therapy Tepotinib Participants received a single oral dose of Tepotinib 500 mg until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal. Tepotinib and Osimertinib Tepotinib Participants received a single oral dose of Tepotinib 500 milligrams (mg) followed by Omisertinib 80 mg once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal. Tepotinib and Osimertinib Osimertinib Participants received a single oral dose of Tepotinib 500 milligrams (mg) followed by Omisertinib 80 mg once daily until disease progression, death, adverse event leading to discontinuation, study withdrawal or consent withdrawal.
- Primary Outcome Measures
Name Time Method Combined Therapy: Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Per Independent Review Committee in Participants With MET Amplification Determined Centrally by Fluorescence in Situ Hybridization(FISH) Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib+Osimertinib): 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) Up to Day 21 of Cycle 1 (each Cycle is of 21 days) DLTs are defined as any of the following toxicities and judged by the Investigator and/or the Sponsor to be not attributable to the disease or disease-related processes under investigation: Grade 4 neutropenia for more than 7 days; Grade greater than or equal to (\>=) 3 febrile neutropenia; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with non-traumatic bleeding; Grade \>= 3 nausea/vomiting and/or diarrhea that has not improved within 72 hours despite adequate and optimal treatment; Any other Grade \>= 3 non-hematological AE, except alopecia or Grade 3 nauseas/vomiting and/or diarrhea that has improved within 72 hours with optimal treatment.
- Secondary Outcome Measures
Name Time Method Monotherapy (Tepotinib): Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1 as Per Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. 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 were defined as events with onset date or worsening during the on-treatment period. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs is defined as reasonably related to the study intervention.
Combined Therapy: Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Per Independent Review Committee in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Related TEAEs Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) The laboratory measurements included hematology, biochemistry, coagulation and urinalysis. Number of participants with clinically significant abnormalities in laboratory values reported as treatment related TEAEs were reported. Clinical significance was decided by investigator.
Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Progression-Free Survival (PFS) According to RECIST Version1.1 as Per Independent Review Committee in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Overall Survival in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing Time from first administration of study treatment to the date of death, assessed approximately up to 42 months Overall survival is defined as the time from first administration of study treatment to the date of death.
Combined Therapy (Tepotinib + Osimertinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy: Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1 Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Progression-Free Survival (PFS) According to RECIST Version1.1 as Assessed by the Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Assessed by the Investigator in Participants With MET Amplification Determined Centrally by FISH time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Combined Therapy ((Tepotinib + Osimertinib): Progression-Free Survival (PFS) According to RECIST Version1.1 as Assessed by the Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Monotherapy (Tepotinib): Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Per Investigator in Participants With MET Amplification Determined Centrally by Fluorescence in Situ Hybridization(FISH) Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD) .CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Monotherapy (Tepotinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Number of Participants With Markedly Abnormal Vital Sign Measurements Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Vital signs included systolic blood pressure (SBP) and diastolic blood pressure (DBP), pulse rate (PR), respiratory rate (RR) body weight (BW) and body temperature (BT). Markedly abnormal value (MAV) criteria for vital signs: SBP and DBP: maximal on treatment (TR) increase or decrease greater than (\>) 40 millimeter of mercury (mmHg); PR: maximal on TR increase or decrease \>40 beats per minute (bpm); RR: maximal on TR increase or decrease \>10 breaths per minute (breaths/minute), BW: maximum on TR increase or decrease \>=10% and BT: maximal on TR increase greater than or equal to (\>=)2 degree Celsius. Number of participants who met the MAV criteria for vital signs at least once post dose were reported.
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. ECOG performance status was reported in terms of number of participants with shifts in score from baseline value vs worst post-baseline value (that is \[i.e.\] highest score).
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Findings Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Electrocardiograms (ECG) was obtained after the participant has been in a semi-supine position for at least 5 min. ECG parameters included heart rate, PQ/PR duration, QRS and QT duration, QT Interval. Clinical significance was determined by the investigator. Number of participants with clinically significant abnormalities in 12-lead ECG were reported.
Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Overall Survival in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment to the date of death, assessed approximately up to 42 months Overall survival is defined as the time from first administration of study treatment to the date of death.
Combined Therapy: Objective Response According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Objective response was defined as percentage of participants with either a confirmed complete response (CR) or partial response (PR) from first administration of study treatment to first observation of progressive disease (PD). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by Blood-Based Next Generation Sequencing Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Monotherapy (Tepotinib): Number of Participants With Confirmed Complete Response (CR) Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Confirmed CR was defined as the disappearance of all evidence of target and non-target lesions.
Monotherapy (Tepotinib): Disease Control Rate Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Monotherapy (Tepotinib): Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Assessed by the Investigator in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Monotherapy (Tepotinib): Duration of Response Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Monotherapy (Tepotinib): Disease Control Rate Assessed by Investigator in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment up to data cutoff (approximately assessed up to 42 months) Disease control rate is defined as the percentage of participants with objective resposne (complete resposne \[CR\] or partial resposne \[PR\] or stable disease \[SD\]). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD while on study. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status) at Safety Follow-up (42 Months) Baseline, safety follow-up (up to 42 months) EORTC QLQ-C30 was 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, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL.
Monotherapy (Tepotinib): Duration of Response Assessed by Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH From first documented objective response to PD or death due to any cause, assessed approximately up to 42 months DOR was defined for participants with objective response, as the time from first documentation of objective response (Complete Response \[CR\] or Partial Response \[PR\]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Change From Baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Visual Analog Scale (VAS) at Safety Follow-up (42 Months) Baseline, safety follow-up (assessed up to 42 months) The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L profile defines health in terms of mobility, self-care, usual activities, pain or discomfort, and anxiety or depression. Each dimension has five levels: 1: no problems, 2: slight problems, 3: moderate problems, 4: severe problems, and 5: extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine.
Combined Therapy (Tepotinib + Osimertinib): Apparent Total Body Clearance (CL/f) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 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) ] CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
Monotherapy (Tepotinib): Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors(RECIST)Version1.1as Assessed by the Independent Review Committee in Participants With MET Amplification Determined Centrally by FISH Time from first administration of study treatment to the date of the first documentation of PD or death due to any cause, assessed approximately up to 42 months PFS was defined as the time is defined as the time from first administration of study treatment to the date of the first documentation of PD or death due to any cause within 126 days of the last tumor assessment, whichever occurs first. PD is defined as at least a 20 % increase in the SLD of target lesion, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
Combined Therapy (Tepotinib + Osimertinib): Change From Baseline in Health-Related Quality of Life as Assessed by Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) at Safety Follow-up (42 Months) Baseline, safety follow-up (up to 42 months) NSCLC-SAQ was a question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 5 domains: cough, pain, dyspnea, fatigue, and appetite. The NSCLC-SAQ score ranged from 0 to 20; High score indicated more severe NSCLC-related symptomatology. mains: cough, pain, dyspnea, fatigue, and appetite.
Combined Therapy (Tepotinib + Osimertinib): Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 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) ] Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule.
Combined Therapy (Tepotinib + Osimertinib): Time to Reach Maximum Observed Plasma Concentration (Tmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 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) ] Tmax was obtained directly from the concentration versus time curve.
Combined Therapy (Tepotinib + Osimertinib): Apparent Volume Of Distribution (Vz/F) of of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 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) ] Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf\*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve.
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) From Day 1 of Cycle 3 up to end of treatment (14 days after last dose, approximately assessed up to 35.6 months) (each Cycle is for 21 days) Percentage of participants with resistant mutations of the EGFR gene or other pathways as assessed in ctDNA were reported.
Combined Therapy (Tepotinib + Osimertinib): Maximum Observed Plasma Concentration (Cmax) of Tepotinib and Its Metabolites (MSC2571109A, MSC2571107A), Osimertinib and Its Metabolite AZD5104 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) ] Cmax was obtained directly from the concentration versus time curve.
Trial Locations
- Locations (179)
Community Health Network
🇺🇸Indianapolis, Indiana, United States
Comprehensive Cancer Centers of Nevada
🇺🇸Las Vegas, Nevada, United States
The First Affiliated Hospital, Zhejiang University
🇨🇳Hangzhou, China
Holy Cross
🇺🇸Fort Lauderdale, Florida, United States
Utah Cancer Specialists
🇺🇸Salt Lake City, Utah, United States
Ventura County Hematology Oncology Specialists
🇺🇸Oxnard, California, United States
Memorial Care
🇺🇸Long Beach, California, United States
Azienda Ospedaliera Universitaria Integrata Verona (Ospedale Borgo Roma) - U.O.C. Oncologia
🇮🇹Verona, Italy
Pius-Hospital Oldenburg - Klinik f. Haematologie und Onkologie
🇩🇪Oldenburg, Germany
Nagoya University Hospital - Dept of Respiratory Medicine
🇯🇵Nagoya-shi, Japan
Saitama Cancer Center
🇯🇵Kitaadachi-gun, Japan
Hamamatsu University School of Medicine, University Hospital - Dept of Respiratory Medicine
🇯🇵Hamamatsu-shi, Japan
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Azienda Socio Sanitaria Territoriale Sette Laghi (Presidio Ospedale di Circolo e Fondazione Macchi) - Oncologia Medica
🇮🇹Varese, Italy
Okayama University Hospital - Dept of Respiratory Medicine/Allergy
🇯🇵Okayama-shi, Japan
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Kindai University Hospital
🇯🇵Osakasayama-shi, Japan
NHO Yamaguchi - Ube Medical Center
🇯🇵Ube-shi, Japan
Chonnam National University Hwasun Hospital
🇰🇷Hwasun-gun, Korea, Republic of
Kurume University Hospital
🇯🇵Kurume-shi, Japan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Kanagawa Cancer Center - Dept of Respiratory Medicine
🇯🇵Yokohama-shi, Japan
Hyogo College of Medicine Hospital - Dept of Respiratory Medicine
🇯🇵Nishinomiya-shi, Japan
Osaka City General Hospital
🇯🇵Osaka-shi, Japan
Hospital Tengku Ampuan Afzan
🇲🇾Kuantan, Malaysia
ICO Badalona - Hospital Germans Trias i Pujol - Servicio de Oncologia Medica
🇪🇸Badalona, Spain
Pham Ngoc Thach Hospital
🇻🇳Ho Chi Minh City, Vietnam
National Lungs Hospital
🇻🇳Hanoi, Vietnam
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
Hospital Regional Universitario de Malaga
🇪🇸Málaga, Spain
ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia
🇪🇸L'Hospitalet de Llobregat, Spain
Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia
🇪🇸Madrid, Spain
Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica
🇪🇸Valencia, Spain
Hospital Universitario Quiron Madrid - Unidad Integral de Oncologia
🇪🇸Pozuelo de Alarcon, Spain
Hospital Universitario Virgen Macarena - Servicio de Oncologia
🇪🇸Sevilla, Spain
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Korea, Republic of
Staedtisches Krankenhaus Kiel
🇩🇪Kiel, Germany
Ospedale Monaldi
🇮🇹Napoli, Italy
Yuma Regional Medical Center
🇺🇸Yuma, Arizona, United States
Compassionate Care Research Group Inc - Edinger Medical Group, Inc.
🇺🇸Fountain Valley, California, United States
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Eastern Connecticut Hematology & Oncology Associates
🇺🇸Norwich, Connecticut, United States
Memorial Healthcare System
🇺🇸Hollywood, Florida, United States
University Cancer and Blood Center
🇺🇸Athens, Georgia, United States
Ocala Oncology
🇺🇸Ocala, Florida, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Fort Wayne Medical Oncology and Hematology
🇺🇸Fort Wayne, Indiana, United States
Beacon Health
🇺🇸South Bend, Indiana, United States
Boston Medical Center - Dept. Hematology/Oncology
🇺🇸Boston, Massachusetts, United States
Pontchartrain
🇺🇸Hammond, Louisiana, United States
Frederick Health- James M Stockman Cancer Institute
🇺🇸Frederick, Maryland, United States
Medstar Franklin Square Clinical Research Center
🇺🇸Baltimore, Maryland, United States
The Center for Cancer & Blood Disorders - Maryland
🇺🇸Bethesda, Maryland, United States
Sparrow Hospital Herbert - Herman Cancer Center
🇺🇸Lansing, Michigan, United States
Central Care Cancer Center (CCCC)
🇺🇸Bolivar, Missouri, United States
St. Louis Cancer Care, LLP
🇺🇸Bridgeton, Missouri, United States
New Jersey Cancer Care and Blood Disorders
🇺🇸Belleville, New Jersey, United States
Summit Medical Group
🇺🇸Florham Park, New Jersey, United States
Mosaic Life Care
🇺🇸Saint Joseph, Missouri, United States
NYU Langone Clinical Cancer Center - NYU Langone Medical Center
🇺🇸New York, New York, United States
NYU Langone Clinical Cancer Center - NYU Langone Medical Cente
🇺🇸New York, New York, United States
OhioHealth
🇺🇸Columbus, Ohio, United States
Southeastern Medical Oncology Center
🇺🇸Goldsboro, North Carolina, United States
Weill Cornell Medical College - Gastroenterology
🇺🇸New York, New York, United States
University Hospitals Seidman
🇺🇸Cleveland, Ohio, United States
Oklahoma Cancer Specialists and Research Institute
🇺🇸Tulsa, Oklahoma, United States
Oregon Oncology Specialists
🇺🇸Salem, Oregon, United States
Gettysburg Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States
Sanford Health
🇺🇸Sioux Falls, South Dakota, United States
Baptist Cancer Center
🇺🇸Memphis, Tennessee, United States
Tennessee Oncology
🇺🇸Nashville, Tennessee, United States
Avera Cancer Institute
🇺🇸Sioux Falls, South Dakota, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
University of Texas MD Anderson Cancer Center - Unit 432 Thoracic Head and Neck Medical Oncology
🇺🇸Houston, Texas, United States
Community Cancer Trials of Utah
🇺🇸Ogden, Utah, United States
Hematology Oncology Associates of Fredericksburg
🇺🇸Fredericksburg, Virginia, United States
UZ Leuven
🇧🇪Gasthuisberg, Belgium
Northwest Medical Specialties
🇺🇸Tacoma, Washington, United States
UZ Antwerpen - Department of Oncology
🇧🇪Edegem, Belgium
AZ Delta
🇧🇪Roeselare, Belgium
Beijing Hospital
🇨🇳Beijing, China
Peking Union Medical College Hospital
🇨🇳Beijing, China
Jilin Cancer Hospital - Oncology
🇨🇳Changchun, China
Peking University Cancer Hospital
🇨🇳Beijing, China
The First Hospital of Jilin University
🇨🇳Changchun, China
Hunan Cancer Hospital
🇨🇳Changsha, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Guangdong General Hospital
🇨🇳Guangzhou, China
Affiliated Tumor Hospital of Harbin Medical University
🇨🇳Harbin, China
Anhui Chest Hospital
🇨🇳Hefei, China
Shanghai Cancer Hospital, Fudan University
🇨🇳Shanghai, China
Linyi Tumor Hospital
🇨🇳Linyi, China
Jiangsu Province Hospital
🇨🇳Nanjing, China
Shanghai Chest Hospital
🇨🇳Shanghai, China
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang, China
The Affiliated Cancer Hospital of Xinjiang Medical university
🇨🇳Urumqi, China
Centre Francois Baclesse - Service d'Oncologie Medicale
🇫🇷Caen Cedex 05, France
Hubei Cancer Hospital
🇨🇳Wuhan, China
Centre Hospitalier Intercommunal de Créteil - Service de Pneumologie
🇫🇷Creteil Cedex, France
Union Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, China
CHU Limoges - Hôpital Dupuytren - Unite d'Oncologie Thoracique et Cutanée
🇫🇷Limoges, France
Centre Léon Bérard
🇫🇷Lyon, France
Universitaetsmedizin Goettingen
🇩🇪Göttingen, Germany
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
Universitaetsklinikum Giessen und Marburg GmbH Standort Giessen
🇩🇪Giessen, Germany
CHU de Toulouse - Hôpital Larrey - Service de Pneumologie et Oncologie Pneumologique
🇫🇷Toulouse, France
Universitaetsklinikum Carl Gustav Carus TU Dresden
🇩🇪Dresden, Germany
Asklepios Fachkliniken Muenchen-Gauting - Abteilung internistische Onkologie
🇩🇪Gauting, Germany
Evangelisches Krankenhaus Hamm GmbH
🇩🇪Hamm, Germany
Thoraxklinik-Heidelberg gGmbH
🇩🇪Heidelberg, Germany
Universitaetsklinikum Koeln - Innere Medizin I, Onkologie, Haematologie
🇩🇪Koeln, Germany
POIS Leipzig GbR
🇩🇪Leipzig, Germany
Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
🇩🇪Luebeck, Germany
Missionsärztliche Klinik
🇩🇪Wuerzburg, Germany
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
IOV - Istituto Oncologico Veneto IRCCS - Oncologia Medica 2
🇮🇹Padova, Italy
Istituto Nazionale Tumori Regina Elena IRCCS - S.C. Oncologia Medica B
🇮🇹Roma, 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
Niigata Cancer Center Hospital - Dept of Internal Medicine
🇯🇵Niigata-shi, Japan
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Pantai Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
Hospital Umum Sarawak
🇲🇾Kuching, Malaysia
BHI of Omsk region "Clinical Oncology Dispensary"
🇷🇺Omsk, Russian Federation
LLC "ClinicaUZI4D"
🇷🇺Pyatigorsk, Russian Federation
Pavlov First Saint Petersburg State Medical University - Research Institute of Pulmunology
🇷🇺St. Petersburg, Russian Federation
LLC "Tonus"
🇷🇺Nizniy Novgorod, Russian Federation
National Cancer Centre - Medical Oncology Pharmacy
🇸🇬Singapore, Singapore
Hospital del Mar - Servicio de Oncologia
🇪🇸Barcelona, Spain
Hospital Universitari Son Espases - Servicio de Oncologia Medica
🇪🇸Palma, Spain
Tri-Service General Hospital
🇨🇳Taipei, Taiwan
Maharaj Nakorn Chiang Mai Hospital
🇹🇭Muang, Thailand
King Chulalongkorn Memorial Hospital
🇹🇭Pathumwan, Thailand
Bach Mai Hospital
🇻🇳Hanoi, Vietnam
K Hospital
🇻🇳Hanoi, Vietnam
Hospital Universitario Materno-Infantil de Canarias - Servicio de Oncologia
🇪🇸Las Palmas de Gran Canaria, Spain
Evangelisches Krankenhaus Hamm gGmbH
🇩🇪Hamm, Germany
Southcoast Center for Cancer Care
🇺🇸Fairhaven, Massachusetts, United States
Cancer Specialists of North Florida
🇺🇸Jacksonville, Florida, United States
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Hospital Pulau Pinang - Clinic Respiratory
🇲🇾Pulau Pinang, Malaysia
China Medical University Hospital
🇨🇳Taichung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
"VitaMed" LLC
🇷🇺Moscow, Russian Federation
Sunway Medical Centre
🇲🇾Petaling Jaya, Selangor, Malaysia
Beacon International Specialist Centre Sdn Bhd
🇲🇾Selangor, Malaysia
Maastricht University Medical Center - Dept of Medical Oncology
🇳🇱Maastricht, Netherlands
SBHI "Krasnoyarsk Regional Oncology Dispensary n.a. A.I. Kryzhanovsky"
🇷🇺Krasnoyarsk, Russian Federation
Icon Cancer Centre
🇸🇬Connexion, Singapore
Cho Ray Hospital
🇻🇳Ho Chi Minh City, Vietnam
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
🇷🇺Saint-Petersburg, Russian Federation
Siriraj Hospital
🇹🇭Bangkoknoi, Thailand
Songklanagarind Hospital
🇹🇭Hat Yai, Thailand
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
The Netherlands Cancer Institute
🇳🇱Amsterdam, Netherlands
Tan Tock Seng Hospital - CTRU/OCS, Research
🇸🇬Singapore, Singapore
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Chi Mei Medical Center, Liou Ying
🇨🇳Tainan, Taiwan
Universitair Medisch Centrum Groningen - Department of Internal Medicine
🇳🇱Groningen, Netherlands
HCMC Oncology Hospital
🇻🇳Ho Chi Minh city, Vietnam
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Hawaii Cancer Care
🇺🇸Honolulu, Hawaii, United States
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
Fujian Cancer Hospital
🇨🇳Fuzhou, China