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

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

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.

Study Overview

• Status: Terminated
• Conditions: Tumor, Solid
• Intervention / Treatment: Drug: BBP-398 (Formerly known as IACS-15509)

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.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010
      • City Of Hope
    • La Jolla, California, United States, 92037
      • Scripps MD Anderson Cancer Center
    • Orange, California, United States, 92868
      • UC Irvine Health
    • Santa Monica, California, United States, 90404
      • UCLA Hematology/Oncology - Santa Monica
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77096
      • The University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Virginia
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Institute for Research & Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; 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).	Drug: BBP-398 (Formerly known as IACS-15509); oral capsules
Experimental: Dose Expansion; 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	Drug: BBP-398 (Formerly known as IACS-15509); oral capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Navire Pharma Inc., a BridgeBio company
• Investigators: Study Director: Lauren Wood, MD, Navire Pharma Inc., a BridgeBio company; Study Director: Susanna Wen, Ms.M, Ph.D, Navire Pharma Inc., a BridgeBio company

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Actual): March 22, 2024
• Study Completion (Actual): July 30, 2024

Study Registration Dates

• First Submitted: July 27, 2020
• First Submitted That Met QC Criteria: August 24, 2020
• First Posted (Actual): August 27, 2020

Study Record Updates

• Last Update Posted (Estimated): December 12, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Cancer; MAPK-pathway alterations
• Other Study ID Numbers: NAV-1001

Drug and device information, study documents

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