Argonaut: SHP2 Inhibitor BBP-398 in Combination With Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Escalation: BBP-398 Level 1 and sotorasib BBP-398 dose Level 1 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle |
Drug: BBP-398
BBP-398 administered orally
Drug: sotorasib
sotorasib administered orally
|
| Experimental: Dose Escalation: BBP-398 Level 2 and sotorasib BBP-398 dose Level 2 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle |
Drug: BBP-398
BBP-398 administered orally
Drug: sotorasib
sotorasib administered orally
|
| Experimental: Dose Escalation: BBP-398 Level 3 and sotorasib BBP-398 dose Level 3 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle |
Drug: BBP-398
BBP-398 administered orally
Drug: sotorasib
sotorasib administered orally
|
| Experimental: Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib BBP-398 Dose Regimen 1 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle |
Drug: BBP-398
BBP-398 administered orally
Drug: sotorasib
sotorasib administered orally
|
| Experimental: Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib BBP-398 Dose Regimen 2 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle |
Drug: BBP-398
BBP-398 administered orally
Drug: sotorasib
sotorasib administered orally
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Phase 1a Dose Escalation Secondary Objectives: Overall Response Rate (ORR) [8 weeks]
Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1
- 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
- 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
- Observed Maximum Plasma Concentration (Cmax) of sotorasib [Cycle 2 Day 1]
Maximum plasma concentration of sotorasib in combination with BBP-398
- 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
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cancer Research SA | Adelaide | South Australia | Australia | 5000 |
Sponsors and Collaborators
- Navire Pharma Inc., a BridgeBio company
- Amgen
Investigators
- Study Director: Lauren Wood, MD, Navire Pharma Inc., a BridgeBio company
- Study Director: Susanna Wen, MsM, PhD, Navire Pharma Inc., a BridgeBio company
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NAV-1003