SHP2 Inhibitor BBP-398 in Combination With Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation
- Conditions
- Metastatic Solid TumorMetastatic NSCLCNon Small Cell Lung CancerSolid Tumor, Adult
- Interventions
- Registration Number
- NCT05480865
- Lead Sponsor
- Navire Pharma Inc., a BridgeBio company
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 28
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation: BBP-398 Level 1 and sotorasib BBP-398 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 Dose Escalation: BBP-398 Level 2 and sotorasib BBP-398 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 Dose Escalation: BBP-398 Level 3 and sotorasib BBP-398 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 Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib BBP-398 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 Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib BBP-398 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 Dose Escalation: BBP-398 Level 1 and sotorasib 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 Dose Escalation: BBP-398 Level 2 and sotorasib 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 Dose Escalation: BBP-398 Level 3 and sotorasib 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 Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib 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 Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib 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
- Primary Outcome Measures
Name Time Method 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
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 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
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) 8 weeks Time from treatment start to progression of disease or death by any cause
Phase 1a Dose Escalation Secondary Objectives: Overall Response Rate (ORR) 8 weeks Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1
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
Observed Maximum Plasma Concentration (Cmax) of sotorasib Cycle 2 Day 1 Maximum plasma concentration of sotorasib in combination with BBP-398
Overall survival (OS) 8 weeks Time from treatment start to death
Half-life (T1/2) of BBP-398 Cycle 2 Day 1 Terminal half-life of BBP-398 in combination with sotorasib
Circulating and intratumoral target engagement biomarkers of BBP-398 activity in combination with sotorasib 24 months Raw, normalized, and/or baseline adjusted analyte signal
Duration of response 8 weeks Defined by RECIST v1.1
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
Time to Cmax (Tmax) of sotorasib Cycle 2 Day 1 Amount of time to reach Cmax of sotorasib in combination with BBP-398
Trial Locations
- Locations (25)
Cancer Research SA
🇦🇺Adelaide, South Australia, Australia
Southern Oncology Clinical Research Unit
🇦🇺Adelaide, South Australia, Australia
Peninsula & South Eastern Haematology and Oncology Group
🇦🇺Frankston, Victoria, Australia
One Clinical Research
🇦🇺Perth, Western Australia, Australia
St John of God Subiaco Hospital
🇦🇺Subiaco, Western Australia, Australia
Orange Health Service
🇦🇺Orange, Australia
Rigshospitalet
🇩🇰Copenhagen, Denmark
Institute Bergonie
🇫🇷Bordeaux, France
Centre Georges François Leclerc
🇫🇷Dijon, France
CHU Grenobles Aples
🇫🇷Grenoble, France
Hopital Bichat-Claude Bernard
🇫🇷Paris, France
CHU de Rennes - Hôpital Pontchaillou
🇫🇷Rennes, France
St. Luke's Hospital S.A.
🇬🇷Thessaloníki, Greece
Careggi University Hospital
🇮🇹Florence, Largo Brambilla, Italy
Spedali Civili - Brescia
🇮🇹Brescia, Italy
Istituto Nazionale Tumori (INT) "Fondazione G. Pascale"
🇮🇹Napoli, Italy
U.O.C Oncoematologia AOU "Luigi Vanvitelli"
🇮🇹Napoli, Italy
Het Nederlands Kanker Instituut - Antoni van Leewenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
Quiron Salud Barcelona
🇪🇸Barcelona, Spain
Vall d'Heborn University Hospital - VHIO
🇪🇸Barcelona, Spain
Clinica Universidad de Navarra
🇪🇸Madrid, Spain
Quiron Salud Madrid
🇪🇸Madrid, Spain
Virgen De La Victoria
🇪🇸Málaga, Spain
Hospital Universitario Virgen De La Macarena
🇪🇸Sevilla, Spain