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

Sponsor

Navire Pharma Inc., a BridgeBio company (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05375084

Collaborator

Bristol-Myers Squibb (Industry)

Enrollment

Location

Arms

32.1

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer Solid Tumor	Drug: BBP-398 with nivolumab	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

45 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

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

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2024

Anticipated Study Completion Date :

Jan 1, 2025

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures

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 [Completion of 1 Cycle (28 days)]
Anti-tumor activity will be defined by objective response rate (ORR) according to RECIST v1.1

Secondary Outcome Measures

Assess preliminary antitumor activity of BBP-398 in combination with nivolumab [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]
Phase 1b Dose Expansion: Assess safety and tolerability of BBP-398 at the RP2D, in combination with nivolumab [Completion of 1 Cycle (28 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.