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

NCT05375084 | Terminated Phase 1 FDA Drug

• 1 other identifier: NAV-1004
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 15

Brief Summary

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.

Conditions

Non Small Cell Lung Cancer; Solid Tumor

Keywords

KRAS mutation; MAPK-pathway alterations; NSCLC; SHP2

Outcome Measures

Primary Outcomes (2)

• Phase 1a Dose Escalation: Assess safety, tolerability, and recommended phase 2 dose (RP2D) of BBP-398 in combination with nivolumab

  Completion of 1 Cycle (28 days)

• Phase 1b Dose Expansion: Assess antitumor activity of BBP-398 in combination with nivolumab

  Anti-tumor activity will be defined by objective response rate (ORR) according to RECIST v1.1

  Completion of 1 Cycle (28 days)

Secondary Outcomes (2)

• Assess preliminary antitumor activity of BBP-398 in combination with nivolumab

  Completion of 1 Cycle (28 days)

• Phase 1b Dose Expansion: Assess safety and tolerability of BBP-398 at the RP2D, in combination with nivolumab

  Completion of 1 Cycle (28 days)

Study Arms (4)

Dose Escalation Level 1

EXPERIMENTAL

Level 1 oral capsules administered in combination with nivolumab

Drug: BBP-398 with nivolumab

Dose Escalation Level 2

EXPERIMENTAL

Level 2 oral capsules administered in combination with nivolumab

Drug: BBP-398 with nivolumab

Dose Escalation Level 3

EXPERIMENTAL

Level 3 oral capsules administered in combination with nivolumab

Drug: BBP-398 with nivolumab

Dose Expansion

EXPERIMENTAL

RP2D defined dose. Oral capsules administered in combination with nivolumab

Drug: BBP-398 with nivolumab

Interventions

BBP-398 with nivolumab DRUG

BBP-398 administered orally once a day (QD); nivolumab administered intravenously every 4 weeks (Q4wks)

Dose Escalation Level 1; Dose Escalation Level 2; Dose Escalation Level 3; Dose Expansion

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Navire Pharma Inc., a BridgeBio company: lead
• Bristol-Myers Squibb: collaborator

Study Sites (15)

Highlands Oncology

Springdale, Arkansas, 72762, United States

Location

Scripps Clinic Torrey Pines

La Jolla, California, 92037, United States

Location

Providence Medical Foundation

Santa Rosa, California, 95403, United States

Location

Memorial Regional Hospital (Memorial Cancer Institute)

Hollywood, Florida, 33021, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21224, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14203, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

University of Pennsylvania (Abramson Cancer Center)

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina (MUSC) - Hollings Cancer Center

Charleston, South Carolina, 29425, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Millennium Research and Clinical Development

Houston, Texas, 77090, United States

Location

NEXT Oncology

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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: May 10, 2022
• First Posted: May 16, 2022
• Study Start: October 20, 2022
• Primary Completion: April 12, 2024
• Study Completion: July 15, 2024
• Last Updated: December 12, 2024

Record last verified: 2024-12

Locations

US (15)