Tepotinib in Solid Tumors Harboring MET Alterations

Sponsor

Chungbuk National University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04647838

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

100

Enrollment

Locations

Arms

55.5

Anticipated Duration (Months)

4.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor MET Exon 14 Skipping Mutation MET Amplification	Drug: Tepotinib	Phase 2

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

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention 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 alterationExperimental: 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)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 16, 2020

Anticipated Primary Completion Date :

Feb 28, 2023

Anticipated Study Completion Date :

Aug 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: NSCLC Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily	Drug: Tepotinib Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily Other Names: MSC2156119J EMD 1214063
Experimental: Other cancers Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily	Drug: Tepotinib Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily Other Names: MSC2156119J EMD 1214063

Arm

Intervention/Treatment

Experimental: NSCLC

Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily

Drug: Tepotinib

Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily

Other Names:

MSC2156119J

EMD 1214063

Experimental: Other cancers

Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily

Drug: Tepotinib

Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily

Other Names:

MSC2156119J

EMD 1214063

Outcome Measures

Primary Outcome Measures

Objective response rates (RECIST1.1) [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.

Secondary Outcome Measures

Progression free survival [Baseline until PD or death within 84 days of last tumor assessment; assessed up to 20 months]
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
Disease control rate [Baseline up to 20 months]
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.
Overall survival [Baseline until death, assessed up to 20 months]
Overall survival is defined as the time (in months) from first trial treatment administration to the date of death.
Toxicity and drug compliance [From the first dose of study drug administration until 33 days after the last dose of study drug administration, assessed up to 20 Months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion 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.
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

Exclusion Criteria:

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.
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
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chonnam National University Hwasun Hospital	Hwasun	Chonnam	Korea, Republic of
2	Chungbuk National University Hospital	Cheongju-si	Chungcheongbuk-do	Korea, Republic of	28644
3	Dankook University Hospital	Cheonan		Korea, Republic of
4	Keimyung University Dongsan Hospital	Daegu		Korea, Republic of
5	Konyang University Hospital	Daejeon		Korea, Republic of
6	National Cancer Center	Goyang-si		Korea, Republic of
7	Hallym University Dongtan Sacred Heart Hospital	Hwaseong-si		Korea, Republic of
8	Gachon University Gil Medical Center	Incheon		Korea, Republic of
9	The Catholic University of Korea Incheon St. Marry Hospital	Incheon		Korea, Republic of
10	Gyeongsang National University Hospital	Jinju		Korea, Republic of
11	Inje University Haeundae Pain Hospital	Pusan		Korea, Republic of
12	Kosin University Gaspel Hospital	Pusan		Korea, Republic of
13	Seoul National University Bundang Hospital	Seongnam-si		Korea, Republic of
14	Chungang University Hospital	Seoul		Korea, Republic of
15	Gangnam Severance Hospital	Seoul		Korea, Republic of
16	Inje University Sanggye Paik Hospital	Seoul		Korea, Republic of
17	Korea University Anam Hospital	Seoul		Korea, Republic of
18	Korea University Guro Hospital	Seoul		Korea, Republic of
19	Samsung Medical Center	Seoul		Korea, Republic of
20	Seoul National University Hospital	Seoul		Korea, Republic of
21	Severance Hospital	Seoul		Korea, Republic of
22	Pusan National University Yangsan Hospital	Yangsan		Korea, Republic of