Metastatic NSCLC, Metastatic Solid Tumor, Non Small Cell Lung Cancer, Solid Tumor, Adult
Conditions
Keywords
KRAS-G12C mutation, SHP2, MAPK-pathway alterations, NSCLC
Brief summary
This is a Phase 1 study of BBP-398, a SHP2 inhibitor, in combination with sotorasib, a KRAS-G12C inhibitor (KRAS-G12Ci), in patients with a KRAS-G12C mutation. The study involves 2 parts: Phase 1a Dose Escalation and Phase 1b Dose Expansion/Optimization.
Detailed description
The primary objectives for Phase 1a Dose Escalation are to evaluate safety and tolerability, and recommend a phase 1b dose (RP1bD) of the combination. The primary objectives for Phase 1b Dose Expansion/Optimization are to evaluate safety and tolerability, and the antitumor activity (defined by the ORR assessed by the investigator according to RECIST v1.1) of BBP-398 when used in combination with sotorasib across two dose regimens in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS-G12C mutation and who are KRAS-G12Ci naïve, and recommend a phase 2 dose (RP2D) of the combination.
Interventions
DRUGBBP-398
BBP-398 administered orally
DRUGsotorasib
sotorasib administered orally
Sponsors
Amgen
Navire Pharma Inc., a BridgeBio company
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Patients must have histologically documented, locally advanced and unresectable, or metastatic solid tumor with documentation of a KRAS-G12C mutation within 2 years 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 all available standard of care therapies. * 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 untreated and/or active CNS metastases. * Patients that have a history of allogenic bone marrow transplant.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a Dose Escalation Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, Serious Adverse Events, and Dose Limiting Toxicities | Completion of 1 Cycle (28 days) | Number of patients experiencing treatment-emergent adverse events, serious adverse events, including changes in lab parameters, vital signs and electrocardiogram changes; duration, and severity based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 |
| Phase 1b Dose Expansion/Optimization Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, and Serious Adverse Events | Completion of 1 Cycle (28 days) | Number of patients experiencing treatment-emergent adverse events, serious adverse events, including changes in lab parameters, vital signs and electrocardiogram changes; duration, and severity based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 |
| Phase 1b Dose Expansion/Optimization Primary Objective: Overall Response Rate (ORR) | 8 weeks | Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 8 weeks | Time from treatment start to death |
| Maximum Observed Plasma Concentration (Cmax) of BBP-398 | Cycle 2 Day 1 | Maximum plasma concentration of BBP-398 in combination with sotorasib |
| Time to Cmax (Tmax) of BBP-398 | Cycle 2 Day 1 | Amount of time to reach Cmax of BBP-398 in combination with sotorasib |
| Area under the plasma concentration-time curve (AUC) of BBP-398 | Cycle 2 Day 1 | Area under the plasma concentration versus time curve of BBP-398 in combination with sotorasib |
| Half-life (T1/2) of BBP-398 | Cycle 2 Day 1 | Terminal half-life of BBP-398 in combination with sotorasib |
| Phase 1a Dose Escalation Secondary Objectives: Overall Response Rate (ORR) | 8 weeks | Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1 |
| Time to Cmax (Tmax) of sotorasib | Cycle 2 Day 1 | Amount of time to reach Cmax of sotorasib in combination with BBP-398 |
| Area under the plasma concentration-time curve (AUC) over dosing interval of sotorasib | Cycle 2 Day 1 | Area under the plasma concentration versus time curve of sotorasib in combination with BBP-398 |
| Half-life (T1/2) of sotorasib | Cycle 2 Day 1 | Terminal half-life of sotorasib in combination with BBP-398 |
| Circulating and intratumoral target engagement biomarkers of BBP-398 activity in combination with sotorasib | 24 months | Raw, normalized, and/or baseline adjusted analyte signal |
| Observed Maximum Plasma Concentration (Cmax) of sotorasib | Cycle 2 Day 1 | Maximum plasma concentration of sotorasib in combination with BBP-398 |
| Duration of response | 8 weeks | Defined by RECIST v1.1 |
| Progression Free Survival (PFS) | 8 weeks | Time from treatment start to progression of disease or death by any cause |
Countries
Australia, Denmark, France, Greece, Italy, Netherlands, Spain
Outcome results
None listed