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

A Phase I, Open Label, Dose Escalation and Expansion, Two- Part Study of SHP-2 Inhibitor BBP-398 to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-cancer Activity in Chinese Subjects With Advanced Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor; Advanced or Metastatic Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: BBP-398

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.

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lei Mu, Master; Phone Number: +86-021-23081188; Email: Lei.mu@lianbio.com

Study Locations

• China
  • Guangdong
    • Guanzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Li Zhang, Master; Phone Number: +86-020-87343458; Email: zhangli@sysucc.org.cn
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Recruiting
      • West China Hospital Sichuan University
      • Contact: Yongsheng Wang, Doctor; Phone Number: 18980602258; Email: wangy756@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 97 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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)

Drug: 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.; Other Names: IACS-15509

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A:Maximum plasma concentration (Cmax) of BBP-398	Maximum plasma concentration of BBP-398 after single and multiple dose administration of BBP-398	Approximately 6 months
Part A:Time to reach Cmax (Tmax) of BBP-398	The amount of time to reach Cmax after single and multiple dose administration of BBP-398	Approximately 6 months
Part A: Terminal half-life (t1/2) of BBP-398	Terminal half-life (t1/2) after single and multiple dose administration of BBP-398	Approximately 6months
Part A: Area under the plasma concentration-time curve (AUC) of BBP-398	Area under the plasma concentration versus time curve after single and multiple dose administration of BBP-398	Approximately 6 months
Part A: Concentration of BBP-398 in urine	To evaluate BBP-398 excretion via urine after single and multiple dose administration of BBP-398.	Approximately 6 months
Part B: Concentration of BBP-398 in plasma	To evaluate BBP-398 plasma concentration after multiple dose administration of BBP-398.	Approximately 6 months

Collaborators and Investigators

• Sponsor: LianBio LLC
• Investigators: Principal Investigator: Li Zhang, Master, West China hospital; Principal Investigator: Yongsheng Wang, Doctor, West China hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2022
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: November 10, 2022
• First Submitted That Met QC Criteria: November 10, 2022
• First Posted (Actual): November 18, 2022

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Solid Tumors, NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: LB1002-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No