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

NCT05621525 | Terminated Phase 1

• 1 other identifier: LB1002-101
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Keywords

Solid Tumors, NSCLC

Outcome Measures

Primary Outcomes (2)

• Determination of Maximum Tolerated Dose (MTD) of BBP-398

  The MTD will be based on DLT

  Completion of 1 Cycle (28 days)

• Determination of anti-tumor activity of BBP-398

  Anti-tumor activity will be defined by objective response rate (ORR, complete response + partial response rate) and duration of response (DOR) according to RECIST v1.1

  Completion of 1 Cycle (28 days)

Secondary Outcomes (6)

• Part A:Maximum plasma concentration (Cmax) of BBP-398

  Approximately 6 months

• Part A:Time to reach Cmax (Tmax) of BBP-398

  Approximately 6 months

• Part A: Terminal half-life (t1/2) of BBP-398

  Approximately 6months

• Part A: Area under the plasma concentration-time curve (AUC) of BBP-398

  Approximately 6 months

• Part A: Concentration of BBP-398 in urine

  Approximately 6 months

Study Arms (1)

Part A Dose Escalation and Part B Dose Expansion

EXPERIMENTAL

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)

Drug: BBP-398

Interventions

BBP-398 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.

Also known as: IACS-15509

Part A Dose Escalation and Part B Dose Expansion

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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

You may not qualify if:

• Patients with a known additional malignancy that is progressing or requires active treatment
• Patients who have previously received a SHP-2 inhibitor
• Patients who are hypersensitivity to SHP-2 inhibitor or any ingredients
• Treatment with any of the related anti-cancer therapies prior to the first dose of BBP-398 within the stated timeframes
• Patients with known active Hepatitis B, Hepatitis C infection, or HIV infection.
• Patients with any of the cardiac-related issues or findings
• Patients with a history of CVA, myocardial infarction or unstable angina within the previous 6 months before starting therapy.
• Patients with known central nervous system (CNS) tumors
• Patients with known active CNS metastases and/or carcinomatous meningitis.
• Patients with persisting toxicity related to prior therapy.
• Patients who have undergone major surgery within 4 weeks prior to study enrollment.
• Pregnant or breastfeeding female patients.
• Patients with inability to swallow oral medications or with gastrointestinal illness that would preclude the absorption of an oral agent.

Sponsors & Collaborators

• LianBio LLC: lead

Study Sites (2)

Sun Yat-sen University Cancer Center

Guanzhou, Guangdong, 510060, China

Location

West China Hospital Sichuan University

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Li Zhang, Master

  West China Hospital

  PRINCIPAL INVESTIGATOR

• Yongsheng Wang, Doctor

  West China Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2022
• First Posted: November 18, 2022
• Study Start: October 18, 2022
• Primary Completion: March 29, 2024
• Study Completion: March 29, 2024
• Last Updated: June 25, 2024

Record last verified: 2024-06

Locations

CN (2)