First-in-Human Study of the SHP2 Inhibitor BBP-398 in Patients With Advanced Solid Tumors
- Conditions
- Tumor, Solid
- Interventions
- Drug: BBP-398 (Formerly known as IACS-15509)
- Registration Number
- NCT04528836
- Lead Sponsor
- Navire Pharma Inc., a BridgeBio company
- Brief Summary
A first-in-human study to evaluate the safety, tolerability and maximum tolerated dose (MTD) and establish the recommended phase 2 dose (RP2D) of BBP-398, a SHP2 inhibitor, in patients with advanced solid tumors.
- Detailed Description
The first-in-human (FIH) study of BBP-398 will be an open-label, sequential-cohort, non-randomized, Phase 1/1B study utilizing BOIN dose escalation followed by an expansion phase in patients with MAPK pathway- or RTK-driven advanced solid tumors. The primary objective is to determine safety and tolerability of BBP-398, the MTD and RP2D. The secondary objectives are to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profile, preliminary anti-tumor activity, objective response rate (ORR, complete response + partial response rate) and the duration of response (DoR) of BBP-398. The exploratory objective is to assess predictive biomarkers of response.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 72
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation BBP-398 (Formerly known as IACS-15509) 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). Dose Expansion BBP-398 (Formerly known as IACS-15509) Oral capsules administered at MTD/RP2D defined dose. Each treatment cycle will be 28 days in duration with BBP-398 administered, once daily (QD) * Cohort A: Advanced or metastatic KRAS mutant solid tumor * Cohort B: Advanced solid tumor with NF1 loss-of-function (LOF) or metastatic BRAF class II/III mutant solid tumor
- Primary Outcome Measures
Name Time Method Determination of Maximum Tolerated Dose (MTD) and establish the RP2D of BBP-398. Completion of 1 Cycle ( 28 days) The MTD will be based on DLT.
- Secondary Outcome Measures
Name Time Method Time to reach Cmax (Tmax) of BBP-398 Approximately 6 weeks The amount of time to reach Cmax after single and multiple dose administration of BBP-398
Determination of anti-tumor activity of BBP-398 After 1 dose of BBP-398 Anti-tumor activity will be defined by objective response rate (ORR2, complete response + partial response rate) and duration of response (DOR3)
Terminal half-life (t1/2) of BBP-398 Approximately 6 weeks Terminal half-life (t1/2) after single and multiple dose administration of BBP-398
Maximum observed plasma concentration (Cmax) of BBP-398 Approximately 6 weeks Maximum plasma concentration of BBP-398 after single and multiple dose administration of BBP-398
Area under the plasma concentration-time curve (AUC) of BBP-398 Approximately 6 weeks Area under the plasma concentration versus time curve after single and multiple dose administration of BBP-398
Trial Locations
- Locations (10)
UCLA Hematology/Oncology - Santa Monica
🇺🇸Santa Monica, California, United States
Sarah Cannon Research Institute
🇺🇸Denver, Colorado, United States
Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
City of Hope
🇺🇸Duarte, California, United States
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Scripps MD Anderson Cancer Center
🇺🇸La Jolla, California, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
MultiCare Institute for Research & Innovation
🇺🇸Tacoma, Washington, United States
NEXT Virginia
🇺🇸Fairfax, Virginia, United States
UC Irvine Health
🇺🇸Orange, California, United States