SHP2 Inhibitor BBP-398 in Combination With Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer With a KRAS Mutation

February 14, 2024 updated by: Navire Pharma Inc., a BridgeBio company

A Phase 1 Study of the SHP2 Inhibitor BBP-398 (Formerly Known as IACS-15509) in Combination With the Programmed Death Receptor-1 Blocking Antibody Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer With a KRAS Mutation

This is a Phase 1 study of BBP-398, a SHP2 inhibitor, in combination with nivolumab, a PD-1 antibody, in patients with NSCLC with a KRAS mutation. The study involves 2 parts: Phase 1a Dose Escalation and Phase 1b Dose Expansion.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The primary objective for Phase 1a Dose Escalation is to evaluate the safety, tolerability, and RP2D of BBP-398, a SHP2 inhibitor, when used in combination with nivolumab in patients with advanced NSCLC with a KRAS mutation who have failed standard of care treatment.

The primary objective for Phase 1b Dose Expansion is to evaluate the antitumor activity of BBP-398, as defined by the ORR (per investigator) according to RECIST v1.1, when used in combination with nivolumab in patients with advanced NSCLC with a KRAS mutation who have failed standard of care treatment.

Study Type

Interventional

Enrollment (Estimated)

45

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Arkansas
      • Springdale, Arkansas, United States, 72762
        • Recruiting
        • Highlands Oncology
        • Contact:
        • Principal Investigator:
          • Eric S Schaefer, MD
    • California
      • La Jolla, California, United States, 92037
      • Santa Rosa, California, United States, 95403
        • Recruiting
        • Providence Medical Foundation
        • Principal Investigator:
          • Ian Anderson, MD
        • Contact:
    • Florida
      • Hollywood, Florida, United States, 33021
        • Recruiting
        • Memorial Regional Hospital (Memorial Cancer Institute)
        • Principal Investigator:
          • Luis E Raez, MD
        • Contact:
          • Tamara Quintana
          • Phone Number: 954-265-4325
          • Email: lraez@mhs.net
        • Contact:
          • Milton Sanchez
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Contact:
        • Principal Investigator:
          • Bruna Pellini, MD
    • Maryland
      • Baltimore, Maryland, United States, 21224
        • Recruiting
        • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Kristen Marrone, MD
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
    • New York
      • Buffalo, New York, United States, 14203
        • Recruiting
        • Roswell Park Cancer Institute
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • Cleveland Clinic
        • Contact:
        • Principal Investigator:
          • Nathan Pennell, MD, PhD
    • Oregon
      • Portland, Oregon, United States, 97213
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • University of Pennsylvania (Abramson Cancer Center)
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Recruiting
        • Medical University of South Carolina (MUSC) - Hollings Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Marcelo V Negrao
      • Houston, Texas, United States, 77090
        • Recruiting
        • Millennium Research and Clinical Development
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • NEXT Oncology
        • Contact:
        • Principal Investigator:
          • Alex Spira

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  • Patients must have histologically documented, locally advanced and unresectable, or metastatic NSCLC with documentation of a KRAS mutation within the 1 year prior to screening.
  • Patients must have measurable disease by RECIST v1.1.
  • Patients must have a minimum life expectancy of >12 weeks after start of study treatment.
  • Patients must have progression or disease recurrence on or after at least one prior line of systemic therapy, which must include platinum-based doublet chemotherapy and anti-PD-(L)1 therapy.
  • Patients must have experienced progressive or recurrent disease occurring either during treatment or within 90 days after discontinuing anti-PD-(L)1 therapy.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.
  • Patients must have adequate organ function.

Key Exclusion Criteria:

  • Patients that have participated in an interventional clinical study within the last 4 weeks.
  • Patients that have received radiotherapy or proton therapy with a limited field of radiation for palliation within 1 week of the start of study treatment, OR radiation to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the start of study treatment.
  • Patients with known central nervous system (CNS) tumors or active CNS metastases.
  • Patients that have experienced progressive disease (PD) within the first 120 days of initiating treatment with an anti- PD-(L)1 agent (e.g., primary refractory).
  • Patients that have a history of allogenic bone marrow transplant.
  • Patients that have select known or suspected autoimmune disease.
  • Patients that have a condition requiring systemic treatment with either corticosteroids (>10 mg prednisone equivalent) or other immunosuppressive medication within 14 days of study start.
  • Patients that have received any live/attenuated vaccine within 30 days of first study treatment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation Level 1
Level 1 oral capsules administered in combination with nivolumab
Drug: BBP-398 with nivolumab
BBP-398 administered orally once a day (QD); nivolumab administered intravenously every 4 weeks (Q4wks)
Experimental: Dose Escalation Level 2
Level 2 oral capsules administered in combination with nivolumab
Drug: BBP-398 with nivolumab
BBP-398 administered orally once a day (QD); nivolumab administered intravenously every 4 weeks (Q4wks)
Experimental: Dose Escalation Level 3
Level 3 oral capsules administered in combination with nivolumab
Drug: BBP-398 with nivolumab
BBP-398 administered orally once a day (QD); nivolumab administered intravenously every 4 weeks (Q4wks)
Experimental: Dose Expansion
RP2D defined dose. Oral capsules administered in combination with nivolumab
Drug: BBP-398 with nivolumab
BBP-398 administered orally once a day (QD); nivolumab administered intravenously every 4 weeks (Q4wks)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1a Dose Escalation: Assess safety, tolerability, and recommended phase 2 dose (RP2D) of BBP-398 in combination with nivolumab
Time Frame: Completion of 1 Cycle (28 days)
Completion of 1 Cycle (28 days)
Phase 1b Dose Expansion: Assess antitumor activity of BBP-398 in combination with nivolumab
Time Frame: Completion of 1 Cycle (28 days)
Anti-tumor activity will be defined by objective response rate (ORR) according to RECIST v1.1
Completion of 1 Cycle (28 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess preliminary antitumor activity of BBP-398 in combination with nivolumab
Time Frame: Completion of 1 Cycle (28 days)
Anti-tumor activity will be defined by objective response rate (ORR) [escalation], duration of response (DOR) and progression free survival (PFS), as defined by RECIST v1.1. and overall survival (OS) [both escalation and expansion]
Completion of 1 Cycle (28 days)
Phase 1b Dose Expansion: Assess safety and tolerability of BBP-398 at the RP2D, in combination with nivolumab
Time Frame: Completion of 1 Cycle (28 days)
Completion of 1 Cycle (28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Navire Pharma Inc., a BridgeBio company

Collaborators

Bristol-Myers Squibb

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 20, 2022

Primary Completion (Estimated)

July 1, 2024

Study Completion (Estimated)

January 1, 2025

Study Registration Dates

First Submitted

May 10, 2022

First Submitted That Met QC Criteria

May 10, 2022

First Posted (Actual)

May 16, 2022

Study Record Updates

Last Update Posted (Actual)

February 16, 2024

Last Update Submitted That Met QC Criteria

February 14, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NAV-1004

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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