A Study of BPI-452080 in Subjects With Solid Tumors

Study Overview
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Brief Summary
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This open-label Phase 1 study will evaluate the efficacy and safety of BPI-452080 in patients with Solid Tumors

Official Title
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A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of BPI-452080 in Subjects With Solid Tumors

Conditions
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Solid Tumor, Renal Cell Carcinoma, Von Hippel-Lindau Disease

Intervention / Treatment
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* Drug: BPI-452080


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed locally advanced or metastatic solid tumor patients, who had disease progression after standard therapy, intolerable to standard therapy, refuse to standard therapy or for whom no standard therapy exists Dose expansion phase: Arm1：has locally advanced or metastatic ccRCC and has progressed during treatment with at least one prior therapeutic regimen Arm2：Von Hippel-Lindau Disease-Associated Clear Cell Renal Cell Carcinoma Arm3：Other solid tumors Adequate organ function Evaluable lesion required for dose escalation phase and at least 1 measurable lesion required for dose expansion phase Exclusion Criteria: Has received prior treatment with another HIF-2α inhibitor Inadequate wash-out of prior therapies described per protocol, which may include anti-tumor therapies, tumor adjuvant drugs, organ or stem cell transplantation, moderate or strong CYP3A inhibitor or inducer, etc Patients with major surgery within 4 weeks, severe or unstable systemic disease, unstable/symptomatic CNS metastasis, other malignant tumors, ILD, clinical significant cardiac disease, bleeding or embolic disease, active infectious disease, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results, in the opinion of the investigator or medical monitor Pregnancy or lactation

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: Dose Escalation<br>Oral tablets taken in escalating levels to determine MTD/RP2D. Each treatment cycle will be 21 days in duration with BPI-452080 administered once daily. | Drug: BPI-452080<br>* Subjects will receive BPI-452080 until disease progression<br>|
| Experimental: Dose Expansion<br>Oral tablets administered at MTD/RP2D defined dose. Each treatment cycle will be 21 days in duration with BPI-452080 administered once daily. Cohort 1: Locally Advanced or Metastatic ccRCC Cohort 2: VHL disease associated RCC Cohort 3: Other Advanced Solid Tumors | Drug: BPI-452080<br>* Subjects will receive BPI-452080 until disease progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events (AEs) | Safety and tolerability will be assessed by monitoring frequency, duration and severity of adverse events | Through the Phase I, approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum observed concentration | Through the Phase I, approximately 24 months | 
| Tmax | Time to reach maximum observed plasma concentration | Through the Phase I, approximately 24 months | 
| t1/2 | Half-life time | Through the Phase I, approximately 24 months | 
| 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 | 
| Progression free survival (PFS) | The time from the date of randomization to disease progression (PD) or death, whichever occurs first | Through the Phase I, approximately 24 months |