Assess the Anti-tumor Activity and Safety of Glumetinib in Patient With Advanced c-MET-positive Non-Small Cell Lung Cancer
- Conditions
- Advance Non-Small Cell Lung CarcinomaLung Cancer, Non-Small Lung Cancer, NSCLC, Met inhibitor, MET exon14 skipping mutationD008175
- Registration Number
- JPRN-jRCT2051200072
- Lead Sponsor
- Hayashi Hidetoshi
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 24
1. Provide informed consent to participate in this study voluntarily.
2. Male and female patients >= 18 years of age (or having reached the age of majority according to local laws and regulations, if the age is > 18 years).
3. Histologically or cytologically confirmed diagnosis of NSCLC.
4. Patients with stage IIIb or IIIc NSCLC who are not candidates for definitive surgical resection or concurrent chemoradiation or patients with stage IV NSCLC (AJCC version 8).
5. For Phase Ib study, patients should carry at least one of the following MET alterations (by local or Sponsor-designated central laboratory screening):
- METex14 skipping mutation who had previously responded to and later progressed on another MET inhibitor or
- MET amplification (FISH GCN >= 5 or MET/CEP7 ratio >= 2) or
- MET over-expression (IHC3+). Patients harboring METex14 skipping mutation who have been treated with another MET inhibitor, should also meet all of the following requirements:
a) Only one MET inhibitor as monotherapy has been treated previously.
b) Achieved one of the following objective clinical benefits on MET inhibitor treatment:
- Documented confirmed partial or complete response (RECIST)
- Significant and long-lasting (>= 3 months) clinical benefits of stable disease as defined by RECIST
c) Had radiologic progression on MET inhibitor treatment
6. For Phase II study, patients with METex14 skipping mutation in tumor or ctDNA samples (local testing is acceptable for eligibility; all patients in Phase II study will have confirmation of METex14 skipping mutation by Sponsor-designated central laboratory but this result is not necessary for eligibility).
7. Availability of tumor tissue sample (either fresh tumor biopsy or archival tumor tissue sample); ctDNA sample (optional).
8. For Phase II study, patients are either systemic treatment naive (the patients should be chemotherapy intolerance or not eligible for chemotherapy or patients refusing of chemotherapy after well-informed) or no more than 2 prior systemic therapies for the advanced NSCLC. Prior neoadjuvant/adjuvant platinum containing chemotherapy will count as having received prior platinum, provided that disease recurred within 6 months of completion of neoadjuvant/adjuvant therapy.
9. At least one measurable lesion as per RECIST 1.1. (A previously irradiated site lesion may only be counted as a target lesion if there is clear sign of progression since the irradiation.)
10. ECOG Performance Status (PS): 0-1. 11. Adequate bone marrow reserve, renal and liver function:
- Absolute neutrophil count >= 1.5 x 109/L;
- Hemoglobin >= 9 g/dL;
- Platelet count >= 75 x 109/L;
- Serum total bilirubin <= ULN (<= 3 x ULN for patients with Gilbert's syndrome);
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x ULN (<= 5.0 x ULN for patients with hepatic metastasis);
- Creatinine clearance (calculated* or measured value**) >= 50 mL/min *For calculated creatinine clearance (Ccr) value, the eligibility should be determined using the Cockcroft-Gault formula: Male Ccr (mL/min) = body weight (kg) x (140-age)/[72 x creatinine (mg/dL)] Female Ccr (mL/min) = male Ccr x 0.85 ** A measured value - International normalized ratio (INR) < 1.3 (or < 3.0 if on anticoagulation)
1. Patients with targetable activating EGFR mutation, ALK rearrangement, ROS1 rearrangement, BRAF mutation or NTRK fusion that have available standard of care therapies.
2. Patients who have symptomatic CNS metastasis which is neurologically unstable or those who have CNS disease requiring increase in the dose of steroid. (Note: Patients with controlled CNS metastasis can participate in the trial. Before entering the study, patients should have finished radiotherapy, or have received operation for CNS tumor metastasis at least two weeks before. Patients' neurological function must be in a stable state; no new neurological deficit is found during clinical examination and no new problem is found during CNS imaging examinations. If patients need to use steroids to treat CNS metastasis, the therapeutic dose of steroid should be stable for >= 3 months at least two weeks prior to entering the study with treatment dose no more than dexamethasone 4 mg daily or an equivalent dose of steroids.)
3. Prior exposure to MET-directed therapy (except patients harboring METex14 skipping in Phase Ib study).
4. Evidence of past or current primary malignancies other than NSCLC (except for non-melanoma skin cancer, in situ breast cancer or in situ cervical carcinoma and superficial bladder cancer, or other cancer curatively treated and with no evidence of disease for at least 5 years).
5. Subjects with clinically significant cardiovascular disease, including:
- NYHA Class III or higher congestive heart failure;
- History or current evidence of serious uncontrolled ventricular arrhythmias requiring drug therapy;
- Acute myocardial infarction, severe or unstable angina pectoris, coronary artery or peripheral artery bypass graft received within 6 months prior to the first dose;
- Left ventricular ejection fraction (LVEF) < 50%;
- Fridericia's corrected QT interval (QTcF) > 460 ms on ECG conducted during screening;
- Congenital long QT syndrome, or any known history of torsade de pointes (TdP), or family history of unexplained sudden death;
- Clinically uncontrolled hypertension (after standard antihypertensive treatment, systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg);
6. Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2 prior neuropathy.
7. Known HIV infection with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunity infection within the past 12 months; active hepatitis B and hepatitis C. Patients whose test results meet one of the following will not be enrolled:
- for patients in China and Japan, confirmed HIV antibody positive. For patients in the US, patients with a history of HIV but no history of AIDS or an AIDS-defining opportunistic infection are allowed to be enrolled;
- serum HBsAg positive and HBV DNA>200 IU/ml or 1000 copies/mL;
- For patients in Japan, whose results are HBsAg antigen negative; however, when HBsAb or HBcAb positive, the patients whose HBV DNA < 200 IU/ml or 1000 copies/mL could be enrolled.
- serum HCV antibody and HCV RNA positive.
8. Anticancer therapy (including chemotherapy, targeted therapy, biotherapy, hormone therapy or other investigational agents) within 4 weeks or 5 times of half-lives (whichever is shorter) prior to the first dose of the study drug or who have not recovered from the side effect of such therapy.
9. Radical radiation therapy (including radiation ther
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method