Phase I Study of the BBP-398 in Patients With Advance Solid Tumors

NCT ID: NCT05621525

Last Updated: 2024-06-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-18
• Study Completion Date: 2024-03-29

Brief Summary

This is an open label, dose escalation and expansion, two-part Phase I study for SHP-2 inhibitor BBP-398 to evaluate the safety, tolerability, pharmacokinetics, determine MTD and/or RP2D, and preliminary anti- cancer activity in Chinese subjects with advanced solid tumors and in Chinese subjects with advanced or metastatic EGFR-mutant NSCLC.

Detailed Description

The Part A of this phase I trial is an abbreviated dose escalation study of BBP-398 following the USA mono dose escalation study (Study NAV- 1001, clinicaltrials.gov ID NCT04528836). The purpose of this part is to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-cancer activity in Chinese subjects with advanced solid tumors. The Part B of this study is to explore the safety, tolerability and efficacy of BBP-398 in Chinese subjects with advanced or metastatic EGFR- mutant NSCLC at MTD and/or RP2D. This Phase I study will provide supportive data to enable Chinese patients to join the combo dose escalation and expansion studies and/or other clinical trials of BBP-398.

Conditions

Advanced Solid Tumor; Advanced or Metastatic Non-small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A Dose Escalation and Part B Dose Expansion

Part A: Oral capsules taken in escalating levels to determine MTD/RP2D. Each treatment cycle will be 28 days in duration with BBP-398 administered, once daily (QD).

Part B: Oral capsules administered at MTD/RP2D defined dose. Each treatment cycle will be 28 days in duration with BBP-398 administered, once daily (QD)

Group Type: EXPERIMENTAL

BBP-398

Intervention Type: DRUG

BBP-398 (formerly known as IACS-15509) is a potent, selective, orally active allosteric inhibitor of SHP2, a tyrosine phosphatase that plays a key role in the RTK -MAPK signal transduction pathway. Key components of the MAPK pathway include the small GTPase RAS, the serine/threonine-protein kinase RAF, mitogen-activated protein kinase (MEK) and ERK. In cells, SHP2 binds to phosphorylated tyrosine residues in the intracellular domain of RTKs such as the EGFR, leading to activation of the downstream MAPK signaling pathway.

Interventions

BBP-398

BBP-398 (formerly known as IACS-15509) is a potent, selective, orally active allosteric inhibitor of SHP2, a tyrosine phosphatase that plays a key role in the RTK -MAPK signal transduction pathway. Key components of the MAPK pathway include the small GTPase RAS, the serine/threonine-protein kinase RAF, mitogen-activated protein kinase (MEK) and ERK. In cells, SHP2 binds to phosphorylated tyrosine residues in the intracellular domain of RTKs such as the EGFR, leading to activation of the downstream MAPK signaling pathway.

Intervention Type: DRUG

Other Intervention Names

IACS-15509

Eligibility Criteria

Inclusion Criteria

1. Patients must have the ability to understand and the willingness to sign a written informed consent document 2 Patients must be willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other specified study procedures 3. Age ≥18, male or female 4.Dose escalation: locally advanced or metastatic solid tumors Dose expansion: Advanced or metastatic EGFR-mutant NSCLC 5. Patients must have measurable disease by RECIST v1.1. 6. Patients must have an ECOG performance status (PS) ≤2 7.Patients with a life expectancy of ≥12 weeks. 8. Patients must have adequate organ function

Exclusion Criteria

1. Patients with a known additional malignancy that is progressing or requires active treatment

2. Patients who have previously received a SHP-2 inhibitor

3. Patients who are hypersensitivity to SHP-2 inhibitor or any ingredients

4. Treatment with any of the related anti-cancer therapies prior to the first dose of BBP-398 within the stated timeframes

5. Patients with known active Hepatitis B, Hepatitis C infection, or HIV infection.

6. Patients with any of the cardiac-related issues or findings

7. Patients with a history of CVA, myocardial infarction or unstable angina within the previous 6 months before starting therapy.

8. Patients with known central nervous system (CNS) tumors

9. Patients with known active CNS metastases and/or carcinomatous meningitis.

10. Patients with persisting toxicity related to prior therapy.

11. Patients who have undergone major surgery within 4 weeks prior to study enrollment.

12. Pregnant or breastfeeding female patients.

13. Patients with inability to swallow oral medications or with gastrointestinal illness that would preclude the absorption of an oral agent.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

LianBio LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li Zhang, Master

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Yongsheng Wang, Doctor

Role: PRINCIPAL_INVESTIGATOR

West China Hospital

Locations

Sun Yat-sen University Cancer Center

Guanzhou, Guangdong, China

West China Hospital Sichuan University

Chengdu, Sichuan, China

Countries

China

Other Identifiers

LB1002-101

Identifier Type: -

Identifier Source: org_study_id