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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Lymphoma; HCC; NSCLC; Advanced Solid Tumor
• Intervention / Treatment: Drug: BPI-371153

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yuankai Shi, Ph.D; Phone Number: 010-67781331; Email: syuankaipumc@126.com

Study Locations

• China
  • Beijing
    • Chaoyang, Beijing, China, 100021
      • Cancer Institute and Hospital, Chinese Academy of Medical Sciences
      • Contact: Yuankai Shi, Ph.D; Phone Number: 010-67781331; Email: syuankaipumc@126.com
  • Hebei
    • Cangzhou, Hebei, China, 062650
      • Cangzhou Central Hospital
      • Contact: Jinghua Zhang, Ph.D; Email: zhangjinghuazlnk@163.com
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Cancer Hospital
      • Contact: Xiubao Ren, Ph.D; Phone Number: 022-23340123; Email: rwziyi@yahoo.com
    • Tianjin, Tianjin, China, 300070
      • Tianjin Medical University General Hospital
      • Contact: Diansheng Zhong, Ph.D; Phone Number: 022-60817009; Email: zhongdsh@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; 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; Subjects will receive BPI-371153 until disease progression
Experimental: Dose Expansion; 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; Subjects will receive BPI-371153 until disease progression

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.
• Investigators: Principal Investigator: Yuankai Shi, Ph.D, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2022
• Primary Completion (Anticipated): June 1, 2024
• Study Completion (Anticipated): June 1, 2025

Study Registration Dates

• First Submitted: April 18, 2022
• First Submitted That Met QC Criteria: April 18, 2022
• First Posted (Actual): April 22, 2022

Study Record Updates

• Last Update Posted (Actual): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 15, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma
• Other Study ID Numbers: BTP-661611

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No