A Phase 1/2 Study of BPI-361175 in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is a phase I/II, open-label study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of BPI-361175 tablets in patients with advanced solid tumors including advanced Non-small cell Lung cancer (NSCLC).This is a three-stage study, consisting of Phase Ia dose escalation, Phase Ib dose expansion and pivotal Phase II Study. The pivotal Phase II study will be designed based on data generated from the Phase I studies.

Official Title
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A Phase 1/2 Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of BPI-361175 in Subjects With Advanced Solid Tumors

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: BPI-361175


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female ≥ 18 years old; Patients with histologically or cytologically confirmed diagnosis of inoperable locally advanced or recurrent/metastatic non-small cell lung cancer (NSCLC) with EGFR sensitive mutations. Patients must have progressed from or be intolerant to or be unfit for standard treatment, or the standard treatment does not exist; For dose expansion and Phase II, patients must be willing to provide tumor tissues (archived tumor tissue samples within 2 years or fresh tumor tissues) and/or blood samples for central lab testing; Measurable or evaluable disease; Adequate bone marrow, liver, and renal function. Exclusion Criteria: Unstable, symptomatic primary CNS tumors/metastasis or leptomeningeal metastases which are not suitable for enrollment, as judged by investigators; Pregnancy or lactation; Other protocol specified criteria.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I<br>Patients will receive a single dose on Day 1, then after an 7-day wash-out period, repeated dosing, once daily will be initiated(Ia). Patients receive BPI-361175 PO. Cycles repeat every 28 days(Ib). | Drug: BPI-361175<br>* Subjects will receive BPI-361175 until disease progression<br>|
| Experimental: Phase II<br>Patients receive BPI-361175 based on RP2D. | Drug: BPI-361175<br>* Subjects will receive BPI-361175 until disease progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: The adverse events (AEs) | Safety and tolerability will be assessed by monitoring frequency, duration and severity of adverse events (AEs). | Through the Phase I, approximately 24 months | 
| Phase I: Determine the recommended Phase II dose (RP2D) | Number of subjects with dose limiting toxicity | Through the Phase I, approximately 24 months | 
| Phase II: the objective response rate (ORR) | The proportion of patients with complete response (CR) and partial response (PR) in all patients. | Through the Phase II, approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase I: Evaluate the pharmacokinetics of BPI-361175 | Blood plasma concentration | Through the Phase I, approximately 24 months | 
| Phase I: the objective response rate (ORR) | The proportion of patients with complete response (CR) and partial response (PR) in all patients. | Through the Phase I, approximately 24 months | 
| Phase II: Disease control rate (DCR) | The proportion of patients with CR, PR and stable disease (SD) in all patients. | Through the Phase II, approximately 24 months | 
| Phase II: Progression free survival (PFS) | The time from the first study dose to disease progression (PD) or death, whichever occurs first. | Through the Phase II, approximately 24 months | 
| Phase II: Overall survival (OS) | The time from the first study dose to death due to any cause. | Through the Phase II, approximately 24 months | 
| Phase II: Duration of response (DOR) | The time from the first CR or PR to the first PD or death due to any cause. | Through the Phase II, approximately 24 months | 
| Phase II: The adverse events (AEs) | Safety and tolerability will be assessed by monitoring frequency, duration and severity of adverse events (AEs). | Through the Phase II, approximately 24 months | 
| Phase I: Disease control rate (DCR) | The proportion of patients with CR, PR and stable disease (SD) in all patients. | Through the Phase I, approximately 24 months | 
| Phase I: Progression free survival (PFS) | The time from the first study dose to disease progression (PD) or death, whichever occurs first. | Through the Phase I, approximately 24 months | 
| Phase I: Overall survival (OS) | The time from the first study dose to death due to any cause. | Through the Phase I, approximately 24 months |