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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05369312
• Other study ID #: BTP-661711
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 2022
• Est. completion date: May 1, 2025

Study information

• Verified date: April 2022
• Source: Betta Pharmaceuticals Co., Ltd.
• Contact: Yilong Wu, Ph.D
• Phone: 020-83525210
• Email: syylwu[@]live.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 230
• Est. completion date: May 1, 2025
• Est. primary completion date: May 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• BPI-442096
Subjects will receive BPI-442096 until disease progression

Locations

Country	Name	City	State
China	Guangdong Provincial People's Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital of Sun yat-sen university	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Zhongshan Hospital affiliated to Fudan University	Xuhui	Shanghai
China	Henan Tumor Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Betta Pharmaceuticals Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Determine the recommended Phase II dose (RP2D)	Number of subjects with dose limiting toxicity	Through the Phase I, approximately 24 months
Secondary	Cmax	Maximum observed concentration	Through the Phase I, approximately 24 months
Secondary	Tmax	Time to reach maximum observed plasma concentration	Through the Phase I, approximately 24 months
Secondary	t1/2	Half-life time	Through the Phase I, approximately 24 months
Secondary	AUC0-t	Area under the concentration-time curve from time 0 to t	Through the Phase I, approximately 24 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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