A Phase 1，Open-label Study of BPI-421286 in Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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Evaluate the safety and tolerability of BPI-421286 in adult subjects with advanced solid tumors. Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in adult subjects with advanced solid tumors.

Official Title
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A Phase 1，Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BPI-421286 in Subjects With Advanced Solid Tumors

Conditions
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Malignant Neoplasms, Metastatic Cancer

Intervention / Treatment
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* Drug: BPI-421286


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically documented, locally-advanced or metastatic malignancy Standard treatment is not available or patient declines Adequate organ function Exclusion Criteria: Active brain metastases from non-brain tumors. Gastrointestinal (GI) tract disease causing the inability to take oral medication. Other protocol specified criteria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dose exploration<br>Enrollment into the dose exploration cohorts may be from any eligible solid tumor type. Dose escalation will begin with 1-6 subjects treated at the lowest planned dose level. If no DLT is observed, dose escalation will continue to the next planned dose cohort | Drug: BPI-421286<br>* Characterize the pharmacokinetics (PK)，safety，effcicay of BPI-421286 following administration as an oral Tablet formulation<br>|
| Experimental: dose expansion<br>dose expansion may proceed with 2 groups consisting of subjects with KRAS p.G12C mutant advanced solid tumors. Dose expansion in these 2 groups may be done concurrently | Drug: BPI-421286<br>* Characterize the pharmacokinetics (PK)，safety，effcicay of BPI-421286 following administration as an oral Tablet formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the safety and tolerability of BPI-421286 in subjects with advanced solid tumor malignancies | Number of subjects with treatment related adverse events | 20 months | 
| determine the recommended Phase II dose (RP2D) and preliminarily to develop a suitable dosing regimen | Number of subjects with dose limiting toxicity | 20 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the pharmacokinetics of BPI-421286 | Blood plasma concentration | 20 months | 
| To determine overall response rate (ORR),calculated as the proportion of subjects with confirmed complete (CR) or partial response (PR) to BPI-421286 | Evaluate clinical activity/efficacy of BPI-421286 | 20 months | 
| To evaluate the duration of response (DOR) in subjects with CR or PR as best response | Evaluate clinical activity/efficacy of BPI-421286 | 20 months | 
| to evaluate the disease control rate (DCR) | Evaluate clinical activity/efficacy of BPI-421286 | 20 months | 
| To evaluate progression-free survival (PFS) following initiation of BPI-421286 | Evaluate clinical activity/efficacy of BPI-421286 | 20 months | 
| To evaluate overall (OS) following initiation of BPI-421286 | Evaluate clinical activity/efficacy of BPI-421286 | 20 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antineoplastic Agents, KRAS, NSCLC, Colorectal Cancer, Pancreatic Cancer, KRAS G12C