Phase 1 Study of BPI-460372 in Advanced Solid Tumor Patients

Study Overview
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Brief Summary
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This study is an open-label, single arm, dose escalation and dose expansion phase 1 study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of BPI-460372 in solid tumor patients.

Official Title
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A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of BPI-460372 in Advanced Solid Tumor Patients

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: BPI-460372


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent; Age ≥18, male and female patients； Expected survival ≥ 3 months； Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1; Dose escalation phase: 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: histologically or cytologically confirmed locally advanced Malignant mesothelioma, Epithelioid hemangioendothelioma or other diagnosed solid tumor patients with NF2 defects, YAP/TAZ fusion, LATS1/2 mutations, and other Hippo signaling pathway abnormalities , who had disease progression after standard therapy, intolerable to standard therapy, refuse to standard therapy or for whom no standard therapy exists; Evaluable lesion required for dose escalation phase and at least 1 measurable lesion as per RECIST v1.1 or mRECIST v1.1 required for dose expansion phase; Exclusion Criteria: Patients who have previously received a TEAD inhibitor; Inadequate wash-out of prior therapies described per protocol, which may include anti-tumor therapies, tumor adjuvant drugs, organ or stem cell transplantation，etc； Patients with severe or unstable systemic disease, unstable/symptomatic CNS metastasis, meningeal metastasis and spinal cord compressionother， malignant tumors, cardiac disease, bleeding or embolic disease, infectious disease, conditions affecting drug swallow and absorption, medical history leading to chronic diarrhea, etc; Pregnancy or lactation; Other conditions considered not appropriate to participate in this trial by the investigators.

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-460372 administered, once daily (QD). | Drug: BPI-460372<br>* Subjects will receive BPI-460372 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-460372 administered, once daily (QD) | Drug: BPI-460372<br>* Subjects will receive BPI-460372 until disease progression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| The dose-limiting toxicity | The dose-limiting toxicity | Through the Phase I, approximately 24 months | 
| Determine the Maximum Tolerated Dose (MTD) | The MTD will be based on DLT. | Through the Phase I, approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the pharmacokinetics of BPI-460372 | Based on blood plasma concentration | Time Frame: Through the Phase I, approximately 24 months | 
| Evaluate the effectiveness of BPI-460372 | Efficacy assessments (tumor evaluation) will be performed per RECIST1.1 or mRECIST1.1 | Time Frame: Through the Phase I, approximately 24 months |