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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Other
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2023

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.

Interventions

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

Arms, Groups and Cohorts

  • 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).
  • 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 KRAS G12C NSCLC Cohort B: Advanced KRAS G12C non-NSCLC Cohort C: Advanced solid tumor with NF1 loss-of-function (LOF) Cohort D: Advanced EGFR-mutant NSCLC
  • Experimental: Food Effect/PK Cohort
    • BBP-398 Monotherapy

Clinical Trial Outcome Measures

Primary Measures

  • Determination of Maximum Tolerated Dose (MTD) of BBP-398.
    • Time Frame: Completion of 1 Cycle ( 28 days)
    • The MTD will be based on DLT.

Secondary Measures

  • 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)
  • 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
  • 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
  • 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
  • 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

Participating in This Clinical Trial

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 the following 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. Food Effect (FE) Cohort of the Sub-study Only: Patients who have a diet incompatible with the on-study diet, in the opinion of the investigator.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Navire Pharma Inc., a BridgeBio company
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Lauren Wood, MD, Study Director, Navire Pharma Inc., a BridgeBio company
    • Susanna Wen, Ms.M, Ph.D, Study Director, Navire Pharma Inc., a BridgeBio company
  • Overall Contact(s)
    • Hiywot Takkele Clinical Operations Lead, 510-387-0916, Hiywot.Takkele@bridgebio.com

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