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.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer; Pancreatic Cancer; Solid Tumor; Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: BPI-442096

Detailed Description

The first-in-human (FIH) study of BPI-442096 will be an open-label, non-randomized, Phase 1 study utilizing a modified "3+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.

• Study Type: Interventional
• Enrollment (Anticipated): 230
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yilong Wu, Ph.D; Phone Number: 020-83525210; Email: syylwu@live.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University
      • Contact: Yubiao Guo, Ph.D; Phone Number: 020-87608185; Email: guoyubiao@hotmail.com
    • Guangzhou, Guangdong, China, 510080
      • Guangdong Provincial People's Hospital
      • Contact: Yilong Wu, Ph.D; Phone Number: 020-83525210; Email: syylwu@live.cn
  • Henan
    • Zhengzhou, Henan, China, 453100
      • Henan Tumor Hospital
      • Contact: Huijuan Wang, Ph.D; Phone Number: 0371-65587418; Email: 18638561588@163.com
  • Shanghai
    • Xuhui, Shanghai, China, 200032
      • Zhongshan Hospital Affiliated to Fudan University
      • Contact: Tianshu Liu, Ph.D; Phone Number: 021-31587861; Email: liu.tianshu@zs-hospital.sh.cn
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310004
      • Zhejiang Cancer Hospital
      • Contact: Xinmin Yu, Ph.D; Phone Number: 0571-88122168; Email: yuxm@zjcc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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;

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

2

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the recommended Phase II dose (RP2D)	Number of subjects with dose limiting toxicity	Through the Phase I, approximately 24 months
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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Betta Pharmaceuticals Co., Ltd.
• Investigators: Principal Investigator: Yilong Wu, Ph.D, Guangdong Provincial People's Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 1, 2022
• Primary Completion (ANTICIPATED): May 1, 2024
• Study Completion (ANTICIPATED): May 1, 2025

Study Registration Dates

• First Submitted: May 5, 2022
• First Submitted That Met QC Criteria: May 9, 2022
• First Posted (ACTUAL): May 11, 2022

Study Record Updates

• Last Update Posted (ACTUAL): June 21, 2022
• Last Update Submitted That Met QC Criteria: June 15, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: BTP-661711

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