This is an open label phase I/phase II clinical study designed to evaluate the safety, tolerability, pharmacokinetics, preliminary efficacy of Dositinib in participants of locally advanced or metastatic non-small cell lung cancer with positive EGFR mutation.
18-75 years old (including 18 and 75 years old), male or female.
Histologically or cytologically confirmed patients with locally advanced NSCLC (stage IIIB / IIIc) or metastatic NSCLC (stage IV) who are unable to undergo radical surgery or radiotherapy (International Alliance against cancer, 8th Edition, 2017).
Locally advanced or metastatic NSCLC patients who have documentation of disease progression (with imaging evidence) while on previous continuous treatments with EGFR-TKI (such as gefitinib, erlotinib, icotinib, afatinib, etc., excluding the third-generation EGFR TKI drugs), or cannot tolerate the treatments for various reasons (only applicable to dose escalation part).
Patients with confirmed EGFR activating mutations that are sensitive to EGFR TKI at any time after initial diagnosis, in dose escalation part including G719X, exon 19 deletion, L858R, L861Q, in dose expansion part including exon 19 deletion and L858R.
Within 28 days before the first administration of the study treatment, the patients have used any chemotherapy drugs and / or immunotherapy drugs in the previous treatment regimen or clinical study; or have undergone major surgery (excluding vascular access establishment surgery) or received > 30Gy within 28 days before the first administration of the study treatment. In addition to the local palliative radiotherapy for bone metastases, the patient have used an experimental drug or other anticancer drugs in the previous treatment regimen or clinical study within 14 days before the first administration of the study treatment, or stopped using other experimental drugs or anticancer drugs for less than 5 ×half-life (e.g., erlotinib less than 8 days, gefitinib less than 10 days, icotinib less than 2 days, afatinib less than 8 days).
Patients who have used the third generation EGFR TKI drugs (such as Osimertinib, rociletinib (co-1686), olmutinib (hm61713), asp8273, egf816, Mefatinib, Avitinib, etc.).
Patients who participated in other therapeutic clinical trials within one month before the first administration (patients who discontinue the experimental drug after more than five half-lives of the drug can be included in the study).
The patients are using (or cannot stop using) CYP3A4 strong inhibitor or inducer or Chinese herbal medicine with anti-tumor indications.
Sequential
Dositinib mesylate tablets
DrugDose-escalation part: Subjects received 90-1408 at doses of 20, 40, 80, 160, 200 and 240 mg. A single oral dose was administered on Cycle 1 Day 1, then once daily from Day 8 onward. Dosing occurred in the morning, with 21 days of continuous treatment per cycle. Dose-expansion part: Subjects received 90-1408 orally at a dose of 80, 160 and 200 mg, administered once daily for 21 consecutive days per cycle.
Incidence and Severity of Adverse Events (AEs)
AEs are assessed based on NCI CTCAE v5.0.
Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of 90-1408 in Single Administration
Pharmacokinetics (PK): Time to Maximum Plasma Concentration (Tmax) of 90-1408 in Single Administration
Pharmacokinetics (PK): Area Under the Plasma Concentration Curve (AUC) of 90-1408 in Single Administration
Pharmacokinetics (PK): Elimination Half-Life (t1/2) of 90-1408 in Single Administration
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