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

Solid Tumor Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05375084
• Other study ID #: NAV-1004
• Status: Recruiting
• Phase: Phase 1
• Start date: October 20, 2022
• Est. completion date: January 2025

Study information

• Verified date: February 2024
• Source: Navire Pharma Inc., a BridgeBio company
• Contact: Navire Clinical Operations
• Phone: 650-391-9740
• Email: NAV1004ct.gov[@]bridgebio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 45
• Est. completion date: January 2025
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer
• Solid Tumor

Intervention

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

Locations

Country	Name	City	State
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Medical University of South Carolina (MUSC) - Hollings Cancer Center	Charleston	South Carolina
United States	Cleveland Clinic	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	NEXT Oncology	Fairfax	Virginia
United States	Memorial Regional Hospital (Memorial Cancer Institute)	Hollywood	Florida
United States	MD Anderson Cancer Center	Houston	Texas
United States	Millennium Research and Clinical Development	Houston	Texas
United States	Scripps Clinic Torrey Pines	La Jolla	California
United States	University of Pennsylvania (Abramson Cancer Center)	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Medical Foundation	Santa Rosa	California
United States	Highlands Oncology	Springdale	Arkansas
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Navire Pharma Inc., a BridgeBio company	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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	Assess preliminary antitumor activity of BBP-398 in combination with nivolumab	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)
Secondary	Phase 1b Dose Expansion: Assess safety and tolerability of BBP-398 at the RP2D, in combination with nivolumab		Completion of 1 Cycle (28 days)