Solid TumorPhase 2NCT04647838
Tepotinib in Solid Tumors Harboring MET Alterations
A Phase 2 study testing Tepotinib in people with Solid Tumor and MET Exon 14 Skipping Mutation, run by Chungbuk National University Hospital at 22 sites in South Korea.
Trial summary
The aim of this study is to understand efficacy of tepotinib in patients with solid cancers harbouring c-MET amplification or exon 14 mutation who progressed after standard treatment for metastatic disease. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Solid Tumor, MET Exon 14 Skipping Mutation, MET Amplification
- What is being tested?
- Tepotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 22 sitesSouth Korea
- Study dates
- 16 Jan 2020to 31 Aug 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed solid cancers (NSCLC, gastric cancer, colorectal cancer, breast cancer, hepatocellular cancer, head and neck cancer, RCC and other solid cancers)
- Subjects who are not eligible for surgical and/or local-regional therapies or who have progressive disease (PD) after surgical and/or local-regional therapies
- Subjects who have disease progression or are intolerant to the prior standard treatment for advanced solid cancers
- A tumor biopsy (excluding fine needle aspiration and cytology samples) is required for determining MET status (a fresh pretreatment tumor biopsy is recommended but archived tumor sample is acceptable).
- Patients with MET exon 14 skipping mutation detected by NGS method and c-MET copy number gain (≥6.0) in the archival or fresh tumor tissue specimen identified in K-MASTER panel. All genetic findings must be reviewed by the study Molecular Steering Committee, prior to study entry.
- Male or female, 19 years of age or older
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- Measurable disease in accordance with Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). The target lesion that has received previous local therapy should not be considered as measurable unless clear progression has been documented since the therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Signed and dated informed consent indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrollment
- Life expectancy judged by the Investigator of at least 3 months
Who cannot join
- 1. Eligibility criteria:
- Histologically or cytologically confirmed solid cancers (NSCLC, gastric cancer, colorectal cancer, breast cancer, hepatocellular cancer, head and neck cancer, RCC and other solid cancers)
- Subjects who are not eligible for surgical and/or local-regional therapies or who have progressive disease (PD) after surgical and/or local-regional therapies
- Subjects who have disease progression or are intolerant to the prior standard treatment for advanced solid cancers
- A tumor biopsy (excluding fine needle aspiration and cytology samples) is required for determining MET status (a fresh pretreatment tumor biopsy is recommended but archived tumor sample is acceptable).
- Patients with MET exon 14 skipping mutation detected by NGS method and c-MET copy number gain (≥6.0) in the archival or fresh tumor tissue specimen identified in K-MASTER panel. All genetic findings must be reviewed by the study Molecular Steering Committee, prior to study entry.
Show all 35Show fewer
- Male or female, 19 years of age or older
- Measurable disease in accordance with Response Evaluation Criteria in Solid Tumors (RECIST v 1.1). The target lesion that has received previous local therapy should not be considered as measurable unless clear progression has been documented since the therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
- Signed and dated informed consent indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrollment
- Life expectancy judged by the Investigator of at least 3 months
- 2. Exclusion criteria
- Prior treatment with any agent targeting the HGF/c-MET pathway
- Prior EGFR therapy for EGFR activating mutant NSCLC
- Patients who received local treatment within 4 weeks prior to the first administration of tepotinib (e.g., major surgery, radiation therapy, hepatic arterial embolization, transcatheter arterial chemoembolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation). NOTE: palliative radiotherapy should be completed at least 7 days prior to the first administration of the tepotinib.
- Prior history of organ transplant
- Laboratory index at screening(refer to protocol)
- Past or current history of neoplasm other than current cancer, except for curatively treated non-melanoma skin cancer, in situ carcinoma of the cervix, node-negative thyroid cancer or other cancer curatively treated and with no evidence of disease for at least 3 years
- Known central nervous system (CNS) or brain metastasis that is either symptomatic or untreated
- Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested products
- Clinically significant gastrointestinal bleeding within 4 weeks prior to the first administration of tepotinib.
- Impaired cardiac function(refer to protocol)
- Hypertension uncontrolled by standard therapies (not stabilized to ≤ 150/90 mmHg)
- Subject with a family history of long QT syndrome or who take any agent that is known to prolong QT/QTc interval or with a marked prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval > 450 msec)
- Known human immunodeficiency virus (HIV) infection
- Subjects who were diagnosed with acute pancreatitis and/or chronic pancreatitis by related symptoms or imaging study.
- Known or suspected drug hypersensitivity to any ingredients of tepotinib
- Female subjects who are pregnant or lactating, or males and females of reproductive potential not willing or not able to employ a highly effective method of birth control/contraception to prevent pregnancy from 2 weeks before receiving study drug until 3 months after receiving the last dose of study drug. A highly effective method of contraception is defined as having a low failure rate (< 1% per year) when used consistently and correctly.
- Concurrent treatment with anti-cancer therapy
- Substance abuse, other acute or chronic medical or psychiatric condition that may increase the risk associated with trial participation in the opinion of the Investigator
- Participation in another interventional clinical trial within 28 days prior to the first administration of tepotinib or within a time period that is less than the cycle length for the investigational treatment (whichever is shorter), or if the subject has any AE caused by the investigational treatment that has not recovered to Grade 0-1
- Previous anticancer treatment-related toxicities not recovered to baseline or Grade 1 (except alopecia) prior to administratin of tepotinib
- Subjects with any concurrent medical condition or disease that will potentially compromise the conduct of the study at the discretion of the Investigators
- Clinically significant third space fluid accumulation (despite the use of diuretics), e.g., uncontrolled pleural effusion or ascites
- Uncontrolled venous or arterial thromboembolism
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
South Korea22 sites, 3 recruiting
- Recruiting
Dankook University Hospital
Cheonan
Soon Il Lee, avnrt@hanmail.net
- Active, not recruiting
Chungbuk National University Hospital
Cheongju-si, North Chungcheong, 28644
- Active, not recruiting
Keimyung University Dongsan Hospital
Daegu
- Active, not recruiting
Konyang University Hospital
Daejeon
- Active, not recruiting
National Cancer Center
Goyang-si
- Active, not recruiting
Hallym University Dongtan Sacred Heart Hospital
Hwaseong-si
- Active, not recruiting
Chonnam National University Hwasun Hospital
Hwasun, Chonnam
- Active, not recruiting
Gachon University Gil Medical Center
Incheon
- Active, not recruiting
The Catholic University of Korea Incheon St. Marry Hospital
Incheon
- Active, not recruiting
Gyeongsang National University Hospital
Jinju
- Active, not recruiting
Inje University Haeundae Pain Hospital
Pusan
- Active, not recruiting
Kosin University Gaspel Hospital
Pusan
- Recruiting
Seoul National University Bundang Hospital
Seongnam-si
Yu Jeong Kim, cong1005@gmail.com
- Active, not recruiting
Chungang University Hospital
Seoul
- Active, not recruiting
Gangnam Severance Hospital
Seoul
- Active, not recruiting
Inje University Sanggye Paik Hospital
Seoul
- Recruiting
Korea University Anam Hospital
Seoul
Yun Ji Choe, yj_choi@korea.ac.kr
- Active, not recruiting
Korea University Guro Hospital
Seoul
- Active, not recruiting
Samsung Medical Center
Seoul
- Active, not recruiting
Seoul National University Hospital
Seoul
- Active, not recruiting
Severance Hospital
Seoul
- Active, not recruiting
Pusan National University Yangsan Hospital
Yangsan
About this study
Official title: A Phase II Study of Tepotinib in Patients With Solid Cancers Harboring c-MET Amplification or Exon 14 Mutation Who Progressed After Standard Treatment for Advanced/Metastatic Disease
The aim of this study is to understand efficacy of tepotinib in patients with solid cancers harbouring c-MET amplification or exon 14 mutation who progressed after standard treatment for metastatic disease.
Read the detailed description
This study is a basket trial with two strata(NSCLC and other cancer). If MET exon 14 skipping mutation or MET amplification(copy number gain ≥6.0 ) is detected by NGS method, then confirmation of genetic findings by Molecular Steering Committee will be followed. Patient can participate in this trial after confirmation of genetic analysis and reviewing other inclusion/exclusion criteria.
- Being tested
- Tepotinib
- Keywords
- solid tumors, MET Exon 14, MET Amplification, cMET, lung, neoplasm, cMET amplification, METex14, cancer, MET Exon 14 skipping
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TepotinibDrug
Also called MSC2156119J, EMD 1214063
Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily
| Study group | Role | What they receive |
|---|---|---|
| NSCLC | Experimental | Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily Receives: Drug: Tepotinib |
| Other cancers | Experimental | Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily Receives: Drug: Tepotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rates (RECIST1.1)
Objective response will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator.
Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial 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 is 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.
Measured: Baseline up to 20 months
Secondary outcomes (4)
Progression free survival
Progression free survival as assessed by investigators is defined as the time (in months) from the first administration of trial treatment to the date of the first documentation of PD (based on independent review) or death due to any cause within 84 days of the last tumor assessment, whichever occurs first
Measured: Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months
Disease control rate
Objective disease control is defined as either a confirmed CR or PR, or stable disease (SD) lasting at least 12 weeks (84 days) as assessed by investigator. CR: Disappearance of all evidence of target and non-target lesions.
Measured: Baseline up to 20 months
Overall survival
Overall survival is defined as the time (in months) from first trial treatment administration to the date of death.
Measured: Baseline until death, assessed up to 20 months
Toxicity and drug compliance
This outcome measure will be presented as the percentage of subjects with any adverse event (AE). Percentages are calculated using total number of subjects per treatment cohort as the denominator.
Measured: From the first dose of study drug administration until 33 days after the last dose of study drug administration, assessed up to 20 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2020
- Study start16 Jan 2020
- Primary completion28 Feb 2023 (estimated)
- Study completion31 Aug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Experimental: Arm 1\_NSCLC Patients with non-small cell lung cancer (NSCLC) harboring MET alteration Experimental: Arm 2\_Other solid tumors Solid tumors excluding NSCLC harboring MET alteration
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chungbuk National University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Ki Hyeong Lee, M.D., Study chair, Chungbuk National University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04647838
- Sponsor's protocol ID
- KM08
- Status last verified
- Nov 2020
- First submitted
- 23 Nov 2020
- Last updated
- 2 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Tepotinib in Patients With Solid Cancers Harboring c-MET Amplification or Exon 14 Mutation Who Progressed After Standard Treatment for Advanced/Metastatic Disease
- ClinicalTrials.gov ID
- NCT04647838
- Acronym / sponsor ID
- KM08
- Keywords
- solid tumors, MET Exon 14, MET Amplification, cMET, lung, neoplasm, cMET amplification, METex14
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Chungbuk National University HospitalUniversity, hospital or other
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- 16 Jan 2020 (actual)
- Primary completion
- 28 Feb 2023 (estimated)
- Study completion
- 31 Aug 2024 (estimated)
- First posted
- 1 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is to understand efficacy of tepotinib in patients with solid cancers harbouring c-MET amplification or exon 14 mutation who progressed after standard treatment for metastatic disease.
Detailed description
This study is a basket trial with two strata(NSCLC and other cancer). If MET exon 14 skipping mutation or MET amplification(copy number gain ≥6.0 ) is detected by NGS method, then confirmation of genetic findings by Molecular Steering Committee will be followed. Patient can participate in this trial after confirmation of genetic analysis and reviewing other inclusion/exclusion criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Experimental: Arm 1_NSCLC Patients with non-small cell lung cancer (NSCLC) harboring MET alteration Experimental: Arm 2_Other solid tumors Solid tumors excluding NSCLC harboring MET alteration
| Arm | Type | Receives |
|---|---|---|
| NSCLC | Experimental | Drug: TepotinibTepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily |
| Other cancers | Experimental | Drug: TepotinibTepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily |
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Histologically or cytologically confirmed solid cancers (NSCLC, gastric cancer, colorectal cancer, breast cancer, hepatocellular cancer, head and neck cancer, RCC and other solid cancers)
- Subjects who are not eligible for surgical and/or local-regional therapies or who have progressive disease (PD) after surgical and/or local-regional therapies
- Subjects who have disease progression or are intolerant to the prior standard treatment for advanced solid cancers
- A tumor biopsy (excluding fine needle aspiration and cytology samples) is required for determining MET status (a fresh pretreatment tumor biopsy is recommended but archived tumor sample is acceptable).
- Patients with MET exon 14 skipping mutation detected by NGS method and c-MET copy number gain (≥6.0) in the archival or fresh tumor tissue specimen identified in K-MASTER panel. All genetic findings must be reviewed by the study Molecular Steering Committee, prior to study entry.
Key exclusion criteria (35 listed)
- Histologically or cytologically confirmed solid cancers (NSCLC, gastric cancer, colorectal cancer, breast cancer, hepatocellular cancer, head and neck cancer, RCC and other solid cancers)
- Subjects who are not eligible for surgical and/or local-regional therapies or who have progressive disease (PD) after surgical and/or local-regional therapies
- Subjects who have disease progression or are intolerant to the prior standard treatment for advanced solid cancers
- A tumor biopsy (excluding fine needle aspiration and cytology samples) is required for determining MET status (a fresh pretreatment tumor biopsy is recommended but archived tumor sample is acceptable).
- Patients with MET exon 14 skipping mutation detected by NGS method and c-MET copy number gain (≥6.0) in the archival or fresh tumor tissue specimen identified in K-MASTER panel. All genetic findings must be reviewed by the study Molecular Steering Committee, prior to study entry.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TepotinibAlso: MSC2156119J, EMD 1214063Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily | Drug | NSCLC, Other cancers |
Primary outcome
Objective response rates (RECIST1.1)
Time frame: Baseline up to 20 months
Objective response will be determined according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator. Objective response is defined as either a confirmed complete response (CR) or partial response (PR) from first administration of trial 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 is 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.
4 secondary outcomes
Progression free survival
Time frame: Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months
Disease control rate
Time frame: Baseline up to 20 months
Overall survival
Time frame: Baseline until death, assessed up to 20 months
Toxicity and drug compliance
Time frame: From the first dose of study drug administration until 33 days after the last dose of study drug administration, assessed up to 20 Months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ki Hyeong Lee, M.D. study chair
Chungbuk National University Hospital
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tepotinib in people with Solid Tumor and MET Exon 14 Skipping Mutation, run by Chungbuk National University Hospital at 22 sites in South Korea.
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 10 inclusion and 35 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: status not confirmed, as of the sponsor's last update on 2 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in South Korea. 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 phase mean?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ki Hyeong Lee, M.D. (+82432696015, kihlee@chungbuk.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rates (RECIST1.1) (time frame: Baseline up to 20 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 Dec 2020.