First-in-Human Study of the SHP2 Inhibitor BBP-398 in Patients With Advanced Solid Tumors

Tumor, Solid Clinical Trial

Official title:

A Phase 1/1B First-in-Human Study of the SHP2 Inhibitor BBP-398 (Formerly Known as IACS-15509) in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04528836
• Other study ID #: NAV-1001
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 12, 2020
• Est. completion date: February 2025

Study information

• Verified date: March 2024
• Source: Navire Pharma Inc., a BridgeBio company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 130
• Est. completion date: February 2025
• Est. primary completion date: May 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria

• Male and non-pregnant females >18 years old.

• Patients must have a diagnosis of advanced (primary or recurrent) or metastatic solid tumor with MAPK-pathway alterations as assessed by clinically validated and/or FDA-approved molecular diagnostic and no available standard of care or curative therapies (MAPK-pathway alterations include, for example KRASG12C mutant, EGFR-mutant).

• Dose expansion only: Patients with specific genomically defined tumor types will be recruited.

• Patients must have measurable disease by RECIST v1.1.

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2.

• Patients must have adequate organ function.

• Patients must have the ability to understand and the willingness to sign a written informed consent document prior to the initiation of the study and any study procedures.

• Patients must be willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other specified study procedures.

Key Exclusion Criteria

• Patients with known active Hepatitis B, Hepatitis C infection, or HIV infection.

• Patients with a history of CVA, myocardial infarction or unstable angina within the previous 6 months before starting therapy.

• Patients with clinically significant cardiac disease.

• Patients with tumors harboring known activating mutations.

• Patients with a known additional malignancy that is progressing or requires active treatment.

• Patients with known central nervous system (CNS) tumors.

• Patients with known active CNS metastases and/or carcinomatous meningitis.

• Patients who have previously received a SHP2 inhibitor.

• Patients with inability to swallow oral medications or with gastrointestinal illness that would preclude the absorption of an oral agent.

• Patients on dialysis.

• Patients with a life expectancy of =12 weeks after the start of IP according to the investigator's judgement.

• Patients with known intolerance/hypersensitivity to BBP-398 or its excipients.

Related Conditions & MeSH terms

• Tumor, Solid

Intervention

Drug:
• BBP-398 (Formerly known as IACS-15509)
oral capsules

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Sarah Cannon Research Institute	Denver	Colorado
United States	City of Hope	Duarte	California
United States	NEXT Virginia	Fairfax	Virginia
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Scripps MD Anderson Cancer Center	La Jolla	California
United States	UC Irvine Health	Orange	California
United States	Huntsman Cancer Institute	Salt Lake City	Utah
United States	UCLA Hematology/Oncology - Santa Monica	Santa Monica	California
United States	MultiCare Institute for Research & Innovation	Tacoma	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Navire Pharma Inc., a BridgeBio company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determination of Maximum Tolerated Dose (MTD) and establish the RP2D of BBP-398.	The MTD will be based on DLT.	Completion of 1 Cycle ( 28 days)
Secondary	Determination of anti-tumor activity of BBP-398	Anti-tumor activity will be defined by objective response rate (ORR2, complete response + partial response rate) and duration of response (DOR3)	After 1 dose of BBP-398
Secondary	Maximum observed plasma concentration (Cmax) of BBP-398	Maximum plasma concentration of BBP-398 after single and multiple dose administration of BBP-398	Approximately 6 weeks
Secondary	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 weeks
Secondary	Terminal half-life (t1/2) of BBP-398	Terminal half-life (t1/2) after single and multiple dose administration of BBP-398	Approximately 6 weeks
Secondary	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 weeks