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

NCT ID: NCT04528836

Last Updated: 2024-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-11-12

Study Completion Date

2024-07-30

Brief Summary

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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

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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.

Conditions

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Tumor, Solid

Keywords

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Cancer MAPK-pathway alterations

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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).

Group Type EXPERIMENTAL

BBP-398 (Formerly known as IACS-15509)

Intervention Type DRUG

oral capsules

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

Group Type EXPERIMENTAL

BBP-398 (Formerly known as IACS-15509)

Intervention Type DRUG

oral capsules

Interventions

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BBP-398 (Formerly known as IACS-15509)

oral capsules

Intervention Type DRUG

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Navire Pharma Inc., a BridgeBio company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status

City of Hope

Duarte, California, United States

Site Status

Scripps MD Anderson Cancer Center

La Jolla, California, United States

Site Status

UC Irvine Health

Orange, California, United States

Site Status

UCLA Hematology/Oncology - Santa Monica

Santa Monica, California, United States

Site Status

Sarah Cannon Research Institute

Denver, Colorado, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

NEXT Virginia

Fairfax, Virginia, United States

Site Status

MultiCare Institute for Research & Innovation

Tacoma, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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NAV-1001

Identifier Type: -

Identifier Source: org_study_id