Safety, Efficacy and Pharmacokinetic of BPI-9016M in Patients With c-Met- Dysregulated Advanced NSCLC

Safety, Efficacy and Pharmacokinetic of BPI-9016M in Patients With c-Met- Dysregulated Advanced NSCLC: A Phase Ib Study,Open-label,Dose-expansion Study

The main objective of this study is to evaluate the safety, tolerability, efficacy and pharmacokinetics of BPI-9016M in patients with c-Met-dysregulated advanced NSCLC. Biomarkers related to the efficacy of BPI-9016M will be investigated.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: BPI-9016M

Detailed Description

This study was a multicenter, open, single-arm, Ib-stage expanded clinical study.

Part I：On the basis of Ia-stage dose escalation study, a safe and effective dose of -300 mg, 450 mg, 600 mg and 800 mg was selected to enlarge the enrollment study in patients with c-Met-dysregulated advanced NSCLC, and continuously administered until the disease progressed or could not be tolerated, in order to further evaluate the safety, ttolerability, efficacy and pharmacokinetics of BPI-9016M.

Part II：On the basis of the completed research results of Ia stage and part I, a safe and effective dose of 400 mg twice a day (bid) was selected to conduct an expanded enrollment study in NSCLC patients with MET exon 14 skipping alterations, and continuously administered until the disease progressed or could not be tolerated, in order to further evaluate the safety, ttolerability, efficacy and pharmacokinetics of BPI-9016M.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yuankai Shi, MD; Email: syuankai@yahoo.cn

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • Recruiting
      • The Second Affiliated Hospital of Anhui Medical University
      • Contact: hui zhao, MD
  • Beijing
    • Beijing, Beijing, China, 100032
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Mengzhao Wang, MD
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
      • Contact: Ziping Wang, MD
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences
      • Contact: Yuankai Shi, MD; Email: syuankaipumc@126.com
  • Hebei
    • Shijiazhuang, Hebei, China, 050011
      • Not yet recruiting
      • Fourth Hospital of Hebei Medical University
      • Principal Investigator: Mingxia Wang
      • Principal Investigator: Da Jiang, MD
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150081
      • Not yet recruiting
      • Affiliated Cancer Hospital of Harbin Medical University
      • Contact: Yan Yu, MD
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • Recruiting
      • The First Hospital of China Medical University
      • Contact: Yunpeng Liu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed, locally advanced or metastatic NSCLC patients, who is not suitable for surgery or radiotherapy
• Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors(RECIST1.1)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Life expectancy ≥12 weeks
• Must have evidence of positive c-Met protein expression by IHC from either local data or the results of molecular pre-screening evaluations；Must haved evidence of MET exon 14 skipping alterations in blood and/or tissue samples.
• Adequate bone marrow, hepatic, and renal function
• Patients of child bearing potential must agree to take contraception during the study and for 3 months after the last day of treatment
• Signed Informed Consent Form

Exclusion Criteria:

• Prior or current treatment with the type II of c-MET inhibitor or HGF/c-Met antibody therapy
• Confirmed ALK or ROS1 rearrangement
• Prior treatment with targeting agents (Including EGFR tyrosine kinase inhibitors,VEGFR TKIs,the tpye I of MET TKIs, etc.) within 14 days or 5 half-life
• Prior treatment with anticancer agents (Including cytotoxic chemotherapy,radiotherapy, immunotherapy etc.) within 4 weeks
• Brain/meninges metastases unless asymptomatic, stable and not requiring steroids for maintenance
• History of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis which required steroid treatment, or any evidence of clinically active interstitial lung disease, radiological documentation of idiopathic pulmonary fibrosis at baseline; uncontrolled pleural effusion/pericardial effusion
• Any evidence of severe or uncontrolled systemic diseases, including CTCAE 2 or higher active infection, unstable angina pectoris, congestive cardiac failure and severe liver/renal or metabolic disease
• Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
• History of organ transplant; had surgery or severe injury within 4 weeks
• Uncontrolled hypertension（Systolic blood pressure≥160mmHg and/or diastolic blood pressure≥100mmHg ）
• Patients unable to swallow orally administered medication, prior surgical procedures affecting absorption.
• Pregnant (positive pregnancy test) or lactating women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BPI-9016M; Part I：Four dose cohorts will be evaluated, including 300mg, 450mg, 600mg, 800mg. BPI-9016M Tablet will be administered orally to patients once daily for each dose cohort. Part II：400mg BPI-9016M Tablet will be administered orally to patients twice a day.	Drug: BPI-9016M; Part I：Four dose cohorts will be evaluated, including 300mg, 450mg, 600mg, 800mg. BPI-9016M Tablet will be administered orally to patients once daily for each dose cohort. Part II：400mg BPI-9016M Tablet will be administered orally to patients twice a day.; Other Names: No other name so far

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Participants with Adverse Events	18 months
Objective Response Rate	16 weeks
Disease Control Rate	16 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival	24 months
Progression-Free Survival	18 months
AUCss	4 weeks
Css-min	18 months

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Anticipated): November 1, 2024
• Study Completion (Anticipated): November 1, 2024

Study Registration Dates

• First Submitted: October 7, 2016
• First Submitted That Met QC Criteria: October 10, 2016
• First Posted (Estimate): October 11, 2016

Study Record Updates

• Last Update Posted (Actual): September 13, 2021
• Last Update Submitted That Met QC Criteria: September 5, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: BD-CM-I02

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