Safety and Pharmacokinetics of BPI-9016M in Patients With Advanced Solid Tumors

Safety and Pharmacokinetics of BPI-9016M in Patients With Advanced Solid Tumors: A Phase Ia Study, Open-label, Dose-escalation Study

BPI-9016M is a novel, highly potent and selective small-molecule inhibitor of c-Met/Axl kinase. In preclinical studies, it demonstrated strong activity in vitro and in vivo against c-Met/Axl kinase and its downstream signaling targets, and inhibited tumor cell growth. This first-in-human study is conducted to assess the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT), to evaluate the pharmacokinetics, safety and preliminary anti-tumor activity of BPI-9016M with single doses and multiple doses.

Study Overview

• Status: Completed
• Conditions: Solid Tumors
• Intervention / Treatment: Drug: BPI-9016M

Detailed Description

This is a phase Ia study, first-in-human, open-label, dose-escalation study of BPI-9016M administered orally once daily (QD) to patients with locally advanced or metastatic solid tumors.The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single dose and multiple doses of BPI-9016M.

All patients will be followed up for adverse events during the study treatment and 28 days after the last dose of study drug. Subjects of this study will be permitted to continue therapy only when BPI-9016M is well tolerated, and tumor response or stable disease is seen.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences
    • Beijing, Beijing, China, 100032
      • Peking Union College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histologically or cytologically confirmed, locally advanced, or metastatic solid tumor that progressed, or failed to respond to, at least one prior systemic therapy
• Evaluable or measurable disease per Response Evaluation Criteria in Solid Tumors(RECIST1.1)
• Life expectancy ≥3 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Adequate bone marrow, hepatic, and renal function
• Patients of child bearing potential must agree to take contraception during the study and for 90 days after the last day of treatment
• Signed Informed Consent Form

Exclusion Criteria:

• Prior treatment with agents of HGF/c-Met inhibitors or HGF/c-Met antibody(Including Crizotinib,Cabozantinib,Volitinib etc.)
• Any anti-cancer therapy, including chemotherapy, hormonal therapy, biologic therapy or radiotherapy within 4 weeks prior to initiation of study treatment
• History of organ transplant; had surgery or severe injury within 4 weeks
• Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 2, except for alopecia
• Any evidence of severe or uncontrolled systemic diseases, including CTCAE 3 or higher active infection, unstable angina pectoris, congestive cardiac failure and severe liver/renal or metabolic disease
• Pregnant (positive pregnancy test) or lactating women
• Inability to take oral medication, prior surgical procedures affecting absorption, or active peptic ulcer disease
• Brain/meninges metastases unless asymptomatic, stable and not requiring steroids for maintenance
• Active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)
• Inability to comply with study and follow-up procedures
• Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding that, in the investigator's opinion, gives reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or renders the patient at high risk from treatment complications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: BPI-9016M; Seven dose cohorts will be evaluated, including 100mg, 200mg, 300mg, 450mg, 600mg, 800mg, 1000mg. BPI-9016M will be administered orally to patients once daily for each dose cohort.	Drug: BPI-9016M; Seven dose cohorts will be evaluated, including 100mg, 200mg, 300mg, 450mg，600mg, 800mg, 1000mg. BPI-9016M will be administered orally to patients once daily for each dose cohort.; Other Names: No other name currently

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants with Adverse Events	The safety and tolerability variables include adverse events, physical examinations, vital signs (specifically including blood pressure), clinical laboratory evaluations including serum chemistry, hematology(Maximum Tolerated Dose) , and urinalysis (with detailed sediment analysis, proteinuria, and 24-hour urine for collection for protein), and electrocardiograms (ECGs) in triplicate,Incidence and nature of DLTs(Dose-Limiting Toxicity),To determine the MTD (Maximum Tolerated Dose).	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Day 1-3 for single dose, and day 1-21 for steady state	1 month
Half-life time	Day 1-3 for single dose, and day 1-21 for steady state	1 month
Tmax	Time to Cmax	1 month

Other Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	18-24 months

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.
• Investigators: Study Chair: Yuankai Shi, MD, Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences; Study Chair: Pei Hu, MD, Peking Union Medical College Hospital

Publications and helpful links

General Publications

• Hu X, Zheng X, Yang S, Wang L, Hao X, Cui X, Ding L, Mao L, Hu P, Shi Y. First-in-human phase I study of BPI-9016M, a dual MET/Axl inhibitor, in patients with non-small cell lung cancer. J Hematol Oncol. 2020 Jan 16;13(1):6. doi: 10.1186/s13045-019-0834-2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 11, 2015
• Primary Completion (ACTUAL): June 30, 2017
• Study Completion (ACTUAL): November 1, 2017

Study Registration Dates

• First Submitted: May 21, 2015
• First Submitted That Met QC Criteria: June 18, 2015
• First Posted (ESTIMATE): June 23, 2015

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 13, 2021
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: BD-CM-I01

Plan for Individual participant data (IPD)

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