Phase 3 clinical study of gumarontinib for NSCLC with MET overexpression

JRCT ID: jRCT2031240494

Registered date:19/11/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: Non small cell lung cancer with MET overexpression
• Date of first enrollment: 20/12/2024
• Target sample size: 580
• Countries of recruitment: China,Japan,US,Japan
• Study type: Interventional

Intervention(s)

Glumetinib will be administered orally once daily continuously in a 3-week (21-day) treatment cycle.
Docetaxel will be administered by intravenous drip at a recommended dose of 75 mg/m2 over 1 hour once every 3 weeks (21-day) on Day 1 of each 3-week (21-day) cycle.

Outcome(s)

• Primary Outcome: Evaluation on comparing the OS of glumetinib with docetaxel.

Secondary Outcome

Key secondary objective:
Evaluation on comparing the PFS ofglumetinib with docetaxel.
Secondary objectives:
To evaluate other efficacy variables of glumetinib and docetaxel.
To evaluate the safety and tolerability of glumetinib and docetaxel.
To evaluate the effect of glumetinib and docetaxel on patients' quality of life (QoL).

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Include criteria: Locally advanced or metastatic NSCLC patients with MET overexpression (IHC 3+) who are driver gene-negative [definitive absence of EGFR mutations, ALK fusions, ROS1 fusions, MET exon 14 skipping mutation, and no known BRAF, NTRK, RET, KRAS, ERBB2 (HER-2) mutations] and have progressed after prior immunotherapy (anti-PD-1/PD-L1 antibodies) and platinum-based doublet chemotherapy (combination or sequential treatment).

Exclude criteria

1. Prior treatment with MET inhibitor.
2. Docetaxel was included in the prior treatment regimen.
5. Patients with active leptomeningeal disease or uncontrolled, untreated brain metastasis.
7. Having central squamous cell lung cancer with cavitation or hemoptysis (> 50 mL/day).
8. Patients with a history of gastrointestinal disease or surgery, gastrointestinal disorders, or other diseases that may affect the absorption of the study drug (e.g., inability to swallow medication, severe ulcers, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, colitis ulcerative, extensive resection of the stomach and small bowel) within 6 months prior to randomization.
9. Receiving major surgery or having significant traumatic injury within 28 days prior to randomization or having not recovered from major side effects.
10. Having interstitial lung disease (ILD) or drug-induced interstitial pneumonia, noninfectious pneumonitis, including radiation pneumonitis, pulmonary fibrosis, or acute lung disease requiring steroid treatment.
11. Patients with clinically significant pericardial effusion
13. Presence of >= Grade 2 edema and lymphoid tissue edema that cannot be resolved with clinical intervention.
14. Any active malignancy =< 2 years prior to randomization, except for the specific cancer being studied in this study and locally recurrent cancers that have been cured (e.g., resected basal cell or squamous cell skin cancer, superficial bladder cancer, in situ cervical or breast cancer).
18. Any clinically significant toxicities related to prior therapy (eg., surgery, chemotherapy, immunotherapy, radiotherapy, etc.) that have not resolved to =< Grade 1 (per CTCAE 5.0) prior to randomization, or toxicities related to prior therapy that are unstable and clinically significant (except for alopecia and CTCAE Grade 2 peripheral neurotoxicity).
19. Patients with clinically significant cardiovascular disease must meet one of the following criteria:
- History or current evidence of severe and uncontrolled clinically significant arrhythmia;
- Acute myocardial infarction, severe/unstable angina, coronary or peripheral artery bypass grafting, cardiac failure congestive with cardiac function >= NYHA Class III within 6 months prior to the first dose;
- Left ventricular ejection fraction (LVEF) < 50%;
- The screening ECG show QT interval (QTcF) > 460 ms (corrected by Fridricias formula)
- Presence of congenital long QT syndrome, a history of Torsades de Pointe or a family history of unexplained sudden death;
- Uncontrolled hypertension (defined as systolic blood pressure >= 140 mmHg and/or diastolic blood pressure >= 90 mmHg after standard antihypertensive treatment).
20. Known history of human immunodeficiency virus (HIV) infection or known history of acquired immunodeficiency syndrome (AIDS);
21. Active hepatitis B and hepatitis C. Patients will be excluded if they meet any of the following criteria:
a) Serum HBsAg positive and HBV DNA > 200 IU/mL or > 1000 copies/mL;
b) Serum HBsAg negative, or if HBcAb results are positive with HBV DNA > 200 IU/mL or 1000 copies/mL;
c) Serum HCV antibody and HCV RNA positive.

Related Information

• Primary Sponsor: Onishi Shintaro