Phase 1 Study Of BPI-442096 In Advanced Solid Tumor Patients

Study Overview

Phase 1 Study of BPI-442096 in Advanced Solid Tumor Patients

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-442096, a SHP2 inhibitor, in patients with advanced solid tumors.

The first-in-human (FIH) study of BPI-442096 will be an open-label, non-randomized, Phase 1 study utilizing a modified ȣ+3" dose escalation followed by an expansion phase in patients with KRAS G12 mutation, class-3 BRAF mutation, NF1 LOF mutation or RTK mutation, amplification or rearrangement advanced solid tumors. The primary objective is to determine safety and tolerability of BPI-442096, the MTD and RP2D. The secondary objectives are to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profile, preliminary anti-tumor activity of BPI-442096.

Solid Tumor
Non-small Cell Lung Cancer
Pancreatic Cancer
Colorectal Cancer

DRUG: BPI-442096

BTP-661711

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2022-05-05	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2022-06-15
First Submitted that Met QC Criteria 2022-05-09	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2022-06-21
First Posted (ACTUAL) 2022-05-11	Results First Posted N/A	Last Verified 2022-04

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Sequential

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Dose Escalation Oral tablets taken in escalating levels to determine MTD/RP2D. Each treatment cycle will be 21 days in duration with BPI-442096 administered, once daily (QD).	DRUG: BPI-442096 Subjects will receive BPI-442096 until disease progression
EXPERIMENTAL: Dose Expansion Oral tablets administered at MTD/RP2D defined dose. Each treatment cycle will be 21 days in duration with BPI-442096 administered, once daily (QD)	DRUG: BPI-442096 Subjects will receive BPI-442096 until disease progression

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Dose Escalation

Oral tablets taken in escalating levels to determine MTD/RP2D. Each treatment cycle will be 21 days in duration with BPI-442096 administered, once daily (QD).

DRUG: BPI-442096

Subjects will receive BPI-442096 until disease progression

EXPERIMENTAL: Dose Expansion

Oral tablets administered at MTD/RP2D defined dose. Each treatment cycle will be 21 days in duration with BPI-442096 administered, once daily (QD)

DRUG: BPI-442096

Subjects will receive BPI-442096 until disease progression

Primary Outcome Measures	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	Measure Description	Time Frame
Cmax	Maximum observed concentration	Through the Phase I, approximately 24 months
Tmax	Time to reach maximum observed plasma concentration	Through the Phase I, approximately 24 months
t1/2	Half-life time	Through the Phase I, approximately 24 months
AUC0-t	Area under the concentration-time curve from time 0 to t	Through the Phase I, approximately 24 months
the objective response rate (ORR）	The proportion of patients with complete response (CR) and partial response (PR) in all patients	Through the Phase I, approximately 24 months
Disease control rate (DCR）	The proportion of patients with CR, PR and stable disease (SD) in all patients	Through the Phase I, approximately 24 months
Duration of response (DOR）	The time from the first CR or PR to the first PD or death due to any cause	Through the Phase I, approximately 24 months
Progression free survival (PFS)	The time from the date of randomization to disease progression (PD) or death, whichever occurs first	Through the Phase I, approximately 24 months

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Yilong Wu, Ph.D

Phone Number: 020-83525210

Email: syylwu@live.cn

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Signed informed consent;
Age ≥18 and ≤75 years, 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), 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 non-small cell lung cancer, pancreatic cancer, colorectal cancer or other diagnosed solid tumor patients (excluding HCC 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 required for dose expansion phase;
Dose expansion only: Patients must have confirmation of tumour mutation status (including KRAS G12, Class-3 BRAF, NF1 LOF mutations, RTK mutations, amplifications or rearrangements).
Adequate organ function;

Patients who have previously received a SHP2 inhibitor;
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;
Patients with severe or unstable systemic disease, unstable/symptomatic CNS metastasis, other malignant tumors, autoimmune disease, ILD, cardiac disease, bleeding or embolic disease, 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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Yilong Wu, Ph.D, Guangdong Provincial People's Hospital

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Resources

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