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

NCT ID: NCT02478866

Last Updated: 2021-09-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-11
• Study Completion Date: 2017-11-30

Brief Summary

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.

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.

Conditions

Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

BPI-9016M

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

No other name currently

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Betta Pharmaceuticals Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yuankai Shi, MD

Role: STUDY_CHAIR

Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences

Pei Hu, MD

Role: STUDY_CHAIR

Peking Union Medical College Hospital

Locations

Department of Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Peking Union College Hospital

Beijing, Beijing Municipality, China

Countries

China

References

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.

Reference Type: DERIVED

PMID: 31948451 (View on PubMed)

Other Identifiers

BD-CM-I01

Identifier Type: -

Identifier Source: org_study_id