Safety, Tolerability and Pharmacokinetic Profile of BPI-15086 in EGFR T790M Mutation-positive NSCLC Patients

Study Overview
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Brief Summary
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The main objective of this study is to evaluate the safety and tolerability of BPI-15086.

Detailed Description
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The main objective of this study is to evaluate the safety and tolerability of BPI-15086. In addition, the anti-cancer effect of BPI-15086 in EGFR T790M mutation-positive advanced NSCLC patients who have progressed on a previous EGFR tyrosine kinase inhibitor therapy will also be evaluated. Biomarkers related to the efficacy of BPI-15086 will be investigated.

Official Title
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A Phase 1 Study of BPI-15086 in Patients With Epidermal Growth Factor Receptor T790M Mutation-positive Non-Small Cell Lung Cancer Who Have Progressed on Previous EGFR Tyrosine Kinase Inhibitor Therapy

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: BPI-15086


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed, locally advanced or metastatic NSCLC patients, who is not suitable for surgery or radiotherapy Radiological documentation of disease progression while on a previous continuous EGFR TKI (e.g. icotinib, gefitinib, afatinib, neratinib, dacomitnib, or erlotinib) treatment Patients must fulfil one of the following: Confirmation that the tumour harbours EGFR sensitivity mutation (exon 19 deletion, L858R and L861R, G719X) Must have experienced clinical benefit from EGFR TKIs, according to the Jackman criteria Confirmation of T790M mutation positive after disease progression on EGFR TKIs Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 and estimated life expectancy of at least 12 weeks Measurable lesion per Response Evaluation Criteria in Solid Tumors(RECIST1.1) Adequate bone marrow, hepatic, and renal function Women: For pre-menopausal women who have a childbearing potential, they must have a pregnancy test within 7 days before starting treatment. The serum or urine pregnancy test must be negative and must be non-lacking; all patients (whether male or female) should be Adequate barrier contraceptive measures during the entire treatment period and 3 months after the end of treatment Have signed Informed Consent Form Exclusion Criteria: Any other malignancy within 5 years of the first dose of study treatment Radiotherapy for target lesion within 4 weeks of the first dose of study treatment. From the treatment of reversible EGFR TKI drugs (e.g. Ectinib, Gefitinib, Erlotinib) to the first use of drugs, the time did not exceed 8 days or 5 half-lives (take the long time)；Irreversible EGFR TKI drugs (e.g. Alfatinib, Neratinib, Dacomitinib) did not last more than 14 days or 5 half-lives (take the long term) Investigational agents or anticancer drugs (Including cytotoxic chemotherapy) from a previous treatment regimen or clinical study within 14 days of the first dose of study treatment Prior treatment with other third generation EGFR TKIs, including osimertinib, rociletinib, EGF816, olmutinib, ASP8273 and avitinib Brain/meninges metastases unless asymptomatic, stable and not requiring steroids for at least 4 weeks prior to start of study treatment History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease, radiological documentation of idiopathic pulmonary fibrosis at baseline; uncontrolled pleural effusion/pericardial effusion Any evidence of severe or uncontrolled systemic diseases, including CTCAE 2 or higher active infection, uncontrolled hypertension, unstable angina pectoris, congestive cardiac failure and severe liver/renal or metabolic disease Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV) History of organ transplant; had surgery or severe injury within 4 weeks Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG eg, complete left bundle branch block, third degree heart block, second degree heart block, PR interval >240msec, or QRS> 110 msec Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medication known to prolong the QT interval Poorly controlled hyperglycemia(fasting blood glucose level ≥7.0 mmol/L). Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment with the exception of alopecia Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of BPI-15086 It is known that the study drug or any of its excipients (microcrystalline cellulose, lactose, crospovidone, hydroxypropyl cellulose, magnesium stearate) are severely allergic CYP3A4 strong inhibitors or inducers or Chinese herbal medicine for anti-tumor indications were used within 1 week before the first dose Abuse of drugs and medical, psychological or social conditions in patients may interfere with participating in the study or assessment of the results of the study Any condition that is unstable or may compromise patient safety and compliance with the study Researchers believe that patients who are not suitable for treatment with this regimen

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BPI-15086<br>BPI-15086, orally administered daily | Drug: BPI-15086<br>* BPI-15086 is administered once daily with a starting dose of 25 mg in a 21-day cycle. When tolerated, increasing doses of BPI-15086 will be tested in subsequent cohorts, until a maximum tolerated dose is determined.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax |  | 4 weeks | 
| Half life |  | 4 weeks | 
| AUC |  | 4 weeks | 
| Objective Response Rate |  | 12 weeks | 
| Progression-Free Survival |  | 18 months |