Safety and Pharmacokinetics of BPI-9016M in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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BPI-9016M is a novel, highly potent and selective small-molecule inhibitor of c-Met/Axl kinase. In preclinical studies, it demonstrated strong activity in vitro and in vivo against c-Met/Axl kinase and its downstream signaling targets, and inhibited tumor cell growth. This first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of BPI-9016M with single doses and multiple doses.

Detailed Description
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This is a phase Ia study, first-in-human, open-label, dose-escalation study of BPI-9016M administered orally once daily (QD) to patients with locally advanced or metastatic solid tumors.The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single dose and multiple doses of BPI-9016M. All patients will be followed up for adverse events during the study treatment and 28 days after the last dose of study drug. Subjects of this study will be permitted to continue therapy only when BPI-9016M is well tolerated, and tumor response or stable disease is seen.

Official Title
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Safety and Pharmacokinetics of BPI-9016M in Patients With Advanced Solid Tumors: A Phase Ia Study, Open-label, Dose-escalation Study

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: BPI-9016M


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed, locally advanced, or metastatic solid tumor that progressed, or failed to respond to, at least one prior systemic therapy Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors(RECIST1.1) Life expectancy ≥3 months Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Adequate bone marrow, hepatic, and renal function Patients of child bearing potential must agree to take contraception during the study and for 90 days after the last day of treatment Signed Informed Consent Form Exclusion Criteria: Prior treatment with agents of HGF/c-Met inhibitors or HGF/c-Met antibody(Including Crizotinib,Cabozantinib,Volitinib etc.) Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy or radiotherapy within 4 weeks prior to initiation of study treatment History of organ transplant; had surgery or severe injury within 4 weeks Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 2, except for alopecia Any evidence of severe or uncontrolled systemic diseases, including CTCAE 3 or higher active infection, unstable angina pectoris, congestive cardiac failure and severe liver/renal or metabolic disease Pregnant (positive pregnancy test) or lactating women Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease Brain/meninges metastases unless asymptomatic, stable and not requiring steroids for maintenance Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV) Inability to comply with study and follow-up procedures Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications

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-9016M<br>Seven dose cohorts will be evaluated, including 100mg, 200mg, 300mg, 450mg, 600mg, 800mg, 1000mg. BPI-9016M will be administered orally to patients once daily for each dose cohort. | Drug: BPI-9016M<br>* Seven dose cohorts will be evaluated, including 100mg, 200mg, 300mg, 450mg，600mg, 800mg, 1000mg. BPI-9016M will be administered orally to patients once daily for each dose cohort.<br>* Other names: No other name currently;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants with Adverse Events | The safety and tolerability variables include adverse events, physical examinations, vital signs (specifically including blood pressure), clinical laboratory evaluations including serum chemistry, hematology(Maximum Tolerated Dose) , and urinalysis (with detailed sediment analysis, proteinuria, and 24-hour urine for collection for protein), and electrocardiograms (ECGs) in triplicate,Incidence and nature of DLTs(Dose-Limiting Toxicity),To determine the MTD (Maximum Tolerated Dose). | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Day 1-3 for single dose, and day 1-21 for steady state | 1 month | 
| Half-life time | Day 1-3 for single dose, and day 1-21 for steady state | 1 month | 
| Tmax | Time to Cmax | 1 month |