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

NCT04528836 | Terminated Phase 1 FDA Drug

• 1 other identifier: NAV-1001
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 10

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.

Conditions

Tumor, Solid

Keywords

Cancer; MAPK-pathway alterations

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Determination of anti-tumor activity of BBP-398

  After 1 dose of BBP-398

• Maximum observed plasma concentration (Cmax) of BBP-398

  Approximately 6 weeks

• Time to reach Cmax (Tmax) of BBP-398

  Approximately 6 weeks

• Terminal half-life (t1/2) of BBP-398

  Approximately 6 weeks

• Area under the plasma concentration-time curve (AUC) of BBP-398

  Approximately 6 weeks

Study Arms (2)

Dose Escalation

EXPERIMENTAL

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)

Dose Expansion

EXPERIMENTAL

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)

Interventions

BBP-398 (Formerly known as IACS-15509) DRUG

oral capsules

Dose Escalation; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Navire Pharma Inc., a BridgeBio company: lead

Study Sites (10)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

Scripps MD Anderson Cancer Center

La Jolla, California, 92037, United States

Location

UC Irvine Health

Orange, California, 92868, United States

Location

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, 90404, United States

Location

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77096, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

NEXT Virginia

Fairfax, Virginia, 22031, United States

Location

MultiCare Institute for Research & Innovation

Tacoma, Washington, 98405, United States

Location

MeSH Terms

Conditions

Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2020
• First Posted: August 27, 2020
• Study Start: November 12, 2020
• Primary Completion: March 22, 2024
• Study Completion: July 30, 2024
• Last Updated: December 12, 2024

Record last verified: 2024-12

Locations

US (10)