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

Phase 1

Terminated

• Conditions: Advanced Solid Tumor; Advanced or Metastatic Non-small Cell Lung Cancer
• Interventions: Drug: BBP-398

• Registration Number: NCT05621525
• Lead Sponsor: LianBio LLC

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.

Study Timeline

• Study Start: 2022-10-18
• Study First Submitted: 2022-11-10
• Study First Submitted QC: 2022-11-10
• Study First Posted: 2022-11-18
• Primary Completion: 2024-03-29
• Study Completion: 2024-03-29
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-24
• Last Update Posted: 2024-06-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Part A Dose Escalation and Part B Dose Expansion	BBP-398	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)

Primary Outcome Measures

Name	Time	Method
Determination of anti-tumor activity of BBP-398	Completion of 1 Cycle (28 days)	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
Determination of Maximum Tolerated Dose (MTD) of BBP-398	Completion of 1 Cycle (28 days)	The MTD will be based on DLT

Secondary Outcome Measures

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

Trial Locations

Locations (2)

West China Hospital Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Sun Yat-sen University Cancer Center; 🇨🇳 Guanzhou, Guangdong, China