Non Small Cell Lung Cancer, Solid Tumor
Conditions
Keywords
KRAS mutation, MAPK-pathway alterations, NSCLC, SHP2
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.
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.
Interventions
DRUGBBP-398 with nivolumab
BBP-398 administered orally once a day (QD); nivolumab administered intravenously every 4 weeks (Q4wks)
Sponsors
Bristol-Myers Squibb
Navire Pharma Inc., a BridgeBio company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) | — |
Countries
United States
Outcome results
None listed