A Phase 1 Study of BPI-371153 in Subjects With Advanced Solid Tumors or Relapsed/Refractory Lymphoma

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-371153, a PD-L1 Inhibitor, in patients with advanced solid tumors or relapsed/refractory lymphoma.

Official Title
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A Phase 1 Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of BPI-371153 in Subjects With Advanced Solid Tumors or Relapsed/Refractory Lymphoma

Conditions
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Advanced Solid Tumor, Lymphoma, NSCLC, HCC

Intervention / Treatment
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* Drug: BPI-371153


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Dose escalation phase: Age ≥18 and ≤65 years, male and female patients; Dose expansion phase: Age ≥18, 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) or relapsed/refractory lymphoma, 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 or relapsed/metastatic Non-Driver Mutation NSCLC, relapsed/refractory lymphoma, HCC with Child-Pugh A or B(≤ 7 points), or other diagnosed 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; Evaluable lesion required for dose escalation phase and at least 1 measurable lesion as per RECIST v1.1( for other diagnosed solid tumos excluding HCC), mRECIST(for HCC) or Lugano 2014(for lymphoma); Adequate organ function; Exclusion Criteria: Dose escalation phase: Prior immune checkpoint inhibition with anti-programmed cell death-1 (PD1)/programmed death ligand-1(PD-L1) or programmed death ligand-2(PD-L2) therapy; Dose expansion phase: Prior immune checkpoint inhibition with anti-programmed cell death-1 (PD1)/programmed death ligand-1(PD-L1) or programmed death ligand-2(PD-L2) therapy within 28 days prior to treatment. Subjects with a history of a Grade 3 or higher immune-related AE from prior immunotherapies; Prior other specific T cell targeting agents; Use of systemic or absorbable topical corticosteroids therapy(≥ 10 mg/day prednisone or equivalent) two weeks prior to start of treatment. 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, and vaccine; Patients with major surgery within 4 weeks, severe or unstable systemic disease, unstable/symptomatic CNS metastasis, other malignant tumors, autoimmune disease, ILD, clinical significant cardiac disease, bleeding or embolic disease, active 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 capsules taken in escalating levels to determine MTD/RP2D. Each treatment cycle will be 21 days in duration with BPI-371153 administered, once daily (QD). | Drug: BPI-371153<br>* Subjects will receive BPI-371153 until disease progression<br>|
| Experimental: Dose Expansion<br>Oral capsules administered at recommended doses. Each treatment cycle will be 21 days in duration with BPI-371153 administered, once daily (QD). Cohort 1: Advanced NSCLC Cohort 2: Relapsed/refractory lymphoma Cohort 3: Advanced HCC Cohort 4: Other Advanced Solid Tumors | Drug: BPI-371153<br>* Subjects will receive BPI-371153 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 |
| --- | --- | --- |
| Evaluate the pharmacokinetics of BPI-371153 | Based on blood plasma concentration | Through the Phase I, approximately 24 months | 
| Determination of anti-tumor activity of BPI-371153 | Efficacy assessments (tumor evaluation) will be performed per RECIST1.1, mRECIST or Lugano 2014 depending on tumor type. | Through the Phase I, approximately 24 months | 
| To explore the levels of expression of PD-L1 associated with BPI-371153 clinical activity | Based on the levels of expression of PD-L1 and anti-tumor activity of BPI-371153 | Through the Phase I, approximately 24 months |