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

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ClinicalTrials.gov Identifier: NCT04528836
Recruitment Status : Recruiting
First Posted : August 27, 2020
Last Update Posted : February 1, 2023
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Tumor, Solid Drug: BBP-398 (Formerly known as IACS-15509) Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 130 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 12, 2020
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : October 2023

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

Primary Outcome Measures :
  1. Determination of Maximum Tolerated Dose (MTD) and establish the RP2D of BBP-398. [ Time Frame: Completion of 1 Cycle ( 28 days) ]
    The MTD will be based on DLT.

Secondary Outcome Measures :
  1. Determination of anti-tumor activity of BBP-398 [ Time Frame: 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)

  2. Maximum observed plasma concentration (Cmax) of BBP-398 [ Time Frame: Approximately 6 weeks ]
    Maximum plasma concentration of BBP-398 after single and multiple dose administration of BBP-398

  3. Time to reach Cmax (Tmax) of BBP-398 [ Time Frame: Approximately 6 weeks ]
    The amount of time to reach Cmax after single and multiple dose administration of BBP-398

  4. Terminal half-life (t1/2) of BBP-398 [ Time Frame: Approximately 6 weeks ]
    Terminal half-life (t1/2) after single and multiple dose administration of BBP-398

  5. Area under the plasma concentration-time curve (AUC) of BBP-398 [ Time Frame: Approximately 6 weeks ]
    Area under the plasma concentration versus time curve after single and multiple dose administration of BBP-398

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04528836

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Contact: Navire Clinical Operations 650-391-9740 nav1001ct.gov@bridgebio.com

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United States, Alabama
University of Alabama at Birmingham Not yet recruiting
Birmingham, Alabama, United States, 35249
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Principal Investigator         
Principal Investigator: Jyoti Malhotra, MD         
Scripps MD Anderson Cancer Center Not yet recruiting
La Jolla, California, United States, 92037
UC Irvine Health Recruiting
Orange, California, United States, 92868
Contact: Study Coordinator    877-827-8839    ucstudy@hs.uci.edu   
UCLA Hematology/Oncology - Santa Monica Recruiting
Santa Monica, California, United States, 90404
Contact: Clinical Research Coordinator    310-633-8400 ext 16136      
Principal Investigator: Saeed Sadeghi, MD         
United States, Colorado
Sarah Cannon Research Institute Recruiting
Denver, Colorado, United States, 80218
Contact: Study Coordinator    720-754-2610      
Principal Investigator: Gerald Falchook, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77096
Contact: Study Coordinator askMDAnderson    877-632-6789      
Principal Investigator: David Hong, MD         
NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Study Coordinator    210-589-9500      
Principal Investigator: David Sommerhalder, MD         
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Study Coordinator    888-424-2100    cancerinfo@hci.utah.edu   
Principal Investigator: Ignacio Garrido-Laguna, MD         
United States, Virginia
NEXT Virginia Not yet recruiting
Fairfax, Virginia, United States, 22031
United States, Washington
MultiCare Institute for Research & Innovation Not yet recruiting
Tacoma, Washington, United States, 98405
Sponsors and Collaborators
Navire Pharma Inc., a BridgeBio company
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Responsible Party: Navire Pharma Inc., a BridgeBio company
ClinicalTrials.gov Identifier: NCT04528836    
Other Study ID Numbers: NAV-1001
First Posted: August 27, 2020    Key Record Dates
Last Update Posted: February 1, 2023
Last Verified: July 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Navire Pharma Inc., a BridgeBio company:
MAPK-pathway alterations