A Study of BPI-1178 in Patients With Advanced Solid Tumor and HR+/HER2- Breast Cancer

Advanced Solid Tumor Clinical Trial

Official title: A Phase 1/2a Study to Evaluate the Tolerability, Safety, Pharmacokinetics and Efficacy of BPI-1178 Alone in Advanced Solid Tumor and of BPI-1178 in Combination With Endocrine Therapy in Advanced HR+/HER2- Breast Cancer

Status Recruiting

Clinical Trial Summary

BPI-1178 is a novel, orally administered inhibitor of both cyclin-dependent kinase 4（CDK4）and CDK6 kinase activity. This Phase I study is a first-in-human (FIH) clinical trial designed to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of oral BPI-1178 in patients with advanced solid tumors. The Phase IIa trial is designed to investigate the anti-tumor activity and safety of BPI-1178 in combination with endocrine therapy in patients with HR+/HER2-advanced breast cancer and to determine the dosing regimen for combination with endocrine therapy in a later confirmatory study.

Clinical Trial Description

This is a study which consists of phase １study（dose-escalation study、dose-expansion study and PK trial） and phase 2a study.

Phase 1 study will adopt the classical 3+3 dose escalation design, exploring the safety and tolerance of 6 dose cohorts (25mg, 75mg, 150mg, 250mg, 400mg and 500mg) in subjects with advanced solid tumor and determining the maximum tolerated dose of BPI-1178 for phase 2a study.

Phase 2a is an open-label clinical study in subjects of HR+/HER2- breast cancer using 3+3 design, to evaluate the efficacy and safety of BPI-1178 in combination with endocrine therapy. Cohort A is BPI-1178 in combination with fulvestrant for advanced or recurrent HR+/HER2- breast cancer after failure or intolerance of non-fulvestrant first-line endocrine therapy. Cohort B is BPI-1178 in combination with letrozole for advanced or relapse more than 1 year after the end of adjuvant endocrine therapy as first-line treatment.

Phase 1 and 2a consist of screening period (28 days before enrollment), treatment period and follow up period (every 3 months until death or the end of study). Phase 1 study: Subjects in each dose group will first receive a single dose. After a single dose for washout period, if the subject has no dose-limiting toxicity (DLT) related to the investigational product, the subject will enter the continuous dose cycle and receive continuous dose in a 28-day treatment cycle (single daily dose for 3 consecutive weeks/drug withdrawal for 1 week) .Once the maximum tolerated dose (MTD) is reached in phase 1, phase 2a study will explore the dose of BPI-1178 from MTD in combination with fulvestrant or letrozole. Phase 2a study: Subjects in Cohort A and Cohort B with intermittent dosing (3-week continuous dosing followed by 1-week rest) and continuous dosing (28-day continuous dosing) will be received in combination with fulvestrant or letrozole. Each 28-day is a complete treatment cycle during the concomitant-drug period.

Dose limiting toxicity (DLT) will be recorded for the single dose period of 7 days and the multiple dose period up to 28 days in phase 1 study, as well as 28 days after the first dose of BPI-1178 in phase 2a. Efficacy will be evaluated by RECIST v1.1 and the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) every 2 months. Adverse events will be monitored throughout the trial. Other exploration of pharmacokinetic information will be assessed throughout the trial. ;

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Breast Neoplasms

• NCT number: NCT04282031
• Study type: Interventional
• Source: Beta Pharma (Suzhou) Co., Ltd.
• Contact: Wenxiang Lu
• Phone: +86-021-62165501
• Email: wenxiang.lu@betapharma.com
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: June 15, 2020
• Completion date: March 15, 2024