Clinical trial NCT05369312: Phase 1 Study of BPI-442096 in Advanced Solid Tumor Patients
Official title: Phase 1 Study of BPI-442096 in Advanced Solid Tumor Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Solid Tumor
Non-small Cell Lung Cancer
Pancreatic Cancer
Colorectal Cancer
Lead sponsor: Betta Pharmaceuticals Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-05-11
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The adverse events (AEs)
timeFrame: Through the Phase I, approximately 24 months
measure: Determine the recommended Phase II dose (RP2D)
timeFrame: Through the Phase I, approximately 24 months
Secondary outcomes:
measure: Cmax
timeFrame: Through the Phase I, approximately 24 months
measure: Tmax
timeFrame: Through the Phase I, approximately 24 months
measure: t1/2
timeFrame: Through the Phase I, approximately 24 months
measure: AUC0-t
timeFrame: Through the Phase I, approximately 24 months
measure: the objective response rate (ORR）
timeFrame: Through the Phase I, approximately 24 months
measure: Disease control rate (DCR）
timeFrame: Through the Phase I, approximately 24 months
measure: Duration of response (DOR）
timeFrame: Through the Phase I, approximately 24 months
measure: Progression free survival (PFS)
timeFrame: Through the Phase I, approximately 24 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun yat-sen university
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Tumor Hospital
state: Henan
city: Xuhui
country: China
facility: Zhongshan Hospital affiliated to Fudan University
state: Shanghai
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Yilong Wu, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: