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Tepotinib in Solid Tumors Harboring MET Alterations

C

Chungbuk National University Hospital

Status and phase

Enrolling
Phase 2

Conditions

Solid Tumor
MET Exon 14 Skipping Mutation
MET Amplification

Treatments

Drug: Tepotinib

Study type

Interventional

Funder types

Other
Industry

Identifiers

Details and patient eligibility

About

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.

Full 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.

Enrollment

100 estimated patients

Sex

All

Ages

19+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  1. Histologically or cytologically confirmed solid cancers (NSCLC, gastric cancer, colorectal cancer, breast cancer, hepatocellular cancer, head and neck cancer, RCC and other solid cancers)
  2. 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
  3. Subjects who have disease progression or are intolerant to the prior standard treatment for advanced solid cancers
  4. 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).
  5. 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.
  6. Male or female, 19 years of age or older
  7. 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.
  8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1
  9. Signed and dated informed consent indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrollment
  10. Life expectancy judged by the Investigator of at least 3 months

Exclusion criteria

  1. Eligibility criteria:

  2. Histologically or cytologically confirmed solid cancers (NSCLC, gastric cancer, colorectal cancer, breast cancer, hepatocellular cancer, head and neck cancer, RCC and other solid cancers)

  3. 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

  4. Subjects who have disease progression or are intolerant to the prior standard treatment for advanced solid cancers

  5. 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).

  6. 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.

  7. Male or female, 19 years of age or older

  8. 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.

  9. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

  10. Signed and dated informed consent indicating that the subject has been informed of all the pertinent aspects of the trial prior to enrollment

  11. Life expectancy judged by the Investigator of at least 3 months

  12. Exclusion criteria

  13. Prior treatment with any agent targeting the HGF/c-MET pathway

  14. Prior EGFR therapy for EGFR activating mutant NSCLC

  15. 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.

  16. Prior history of organ transplant

  17. Laboratory index at screening(refer to protocol)

  18. 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

  19. Known central nervous system (CNS) or brain metastasis that is either symptomatic or untreated

  20. Medical history of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease, or conditions that may hamper compliance and/or absorption of the tested products

  21. Clinically significant gastrointestinal bleeding within 4 weeks prior to the first administration of tepotinib.

  22. Impaired cardiac function(refer to protocol)

  23. Hypertension uncontrolled by standard therapies (not stabilized to ≤ 150/90 mmHg)

  24. 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)

  25. Known human immunodeficiency virus (HIV) infection

  26. Subjects who were diagnosed with acute pancreatitis and/or chronic pancreatitis by related symptoms or imaging study.

  27. Known or suspected drug hypersensitivity to any ingredients of tepotinib

  28. 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.

  29. Concurrent treatment with anti-cancer therapy

  30. 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

  31. 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

  32. Previous anticancer treatment-related toxicities not recovered to baseline or Grade 1 (except alopecia) prior to administratin of tepotinib

  33. Subjects with any concurrent medical condition or disease that will potentially compromise the conduct of the study at the discretion of the Investigators

  34. Clinically significant third space fluid accumulation (despite the use of diuretics), e.g., uncontrolled pleural effusion or ascites

  35. Uncontrolled venous or arterial thromboembolism

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

100 participants in 2 patient groups

NSCLC
Experimental group
Description:
Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily
Treatment:
Drug: Tepotinib
Other cancers
Experimental group
Description:
Tepotinib 500mg (2 tablets of 250mg) per day D1-21 orally, once daily
Treatment:
Drug: Tepotinib

Trial contacts and locations

22

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Central trial contact

Ki Hyeong Lee, M.D.; Eun Joo Kang, M.D.

Data sourced from clinicaltrials.gov

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