Phase 1 Study of BPI-442096 in Advanced Solid Tumor Patients

Study Overview
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Brief Summary
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A first-in-human study to evaluate the safety, tolerability and maximum tolerated dose (MTD) and establish the recommended phase 2 dose (RP2D) of BPI-442096, a SHP2 inhibitor, in patients with advanced solid tumors.

Detailed Description
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The first-in-human (FIH) study of BPI-442096 will be an open-label, non-randomized, Phase 1 study utilizing a modified 3+3 dose escalation followed by an expansion phase in patients with KRAS G12 mutation, class-3 BRAF mutation, NF1 LOF mutation or RTK mutation, amplification or rearrangement advanced solid tumors. The primary objective is to determine safety and tolerability of BPI-442096, the MTD and RP2D. The secondary objectives are to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profile, preliminary anti-tumor activity of BPI-442096.

Official Title
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Phase 1 Study of BPI-442096 in Advanced Solid Tumor Patients

Conditions
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Solid Tumor, Non-small Cell Lung Cancer, Pancreatic Cancer, Colorectal Cancer

Intervention / Treatment
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* Drug: BPI-442096


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent; Age ≥18 and ≤75 years, male and female patients; Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1; Dose escalation phase: histologically or cytologically confirmed locally advanced or metastatic solid tumor patients (excluding HCC 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 non-small cell lung cancer, pancreatic cancer, colorectal cancer or other diagnosed solid tumor patients (excluding HCC patients), 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 required for dose expansion phase; Dose expansion only: Patients must have confirmation of tumour mutation status (including KRAS G12, Class-3 BRAF, NF1 LOF mutations, RTK mutations, amplifications or rearrangements). Adequate organ function; Exclusion Criteria: Patients who have previously received a SHP2 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; Patients with severe or unstable systemic disease, unstable/symptomatic CNS metastasis, other malignant tumors, autoimmune disease, ILD, 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
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: 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-442096 administered, once daily (QD). | Drug: BPI-442096<br>* Subjects will receive BPI-442096 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-442096 administered, once daily (QD) | Drug: BPI-442096<br>* Subjects will receive BPI-442096 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 | 
| Determine the recommended Phase II dose (RP2D) | Number of subjects with dose limiting toxicity | 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 | 
| AUC0-t | Area under the concentration-time curve from time 0 to t | 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 | 
| 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 | 
| 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 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 |