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

Advanced Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05621525
• Other study ID #: LB1002-101
• Status: Recruiting
• Phase: Phase 1
• Start date: October 18, 2022
• Est. completion date: September 2024

Study information

• Verified date: December 2023
• Source: LianBio LLC
• Contact: Lei Mu, Master
• Phone: +86-021-23081188
• Email: Lei.mu[@]lianbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 28
• Est. completion date: September 2024
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced or Metastatic Non-small Cell Lung Cancer
• Advanced Solid Tumor
• Carcinoma, Non-Small-Cell Lung
• Neoplasms

Intervention

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.

Locations

Country	Name	City	State
China	West China Hospital Sichuan University	Chengdu	Sichuan
China	Sun Yat-sen University Cancer Center	Guanzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
LianBio LLC

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of Maximum Tolerated Dose (MTD) of BBP-398	The MTD will be based on DLT	Completion of 1 Cycle (28 days)
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part B: Concentration of BBP-398 in plasma	To evaluate BBP-398 plasma concentration after multiple dose administration of BBP-398.	Approximately 6 months