SHP2 Inhibitor BBP-398 in Combination With Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation (Argonaut)
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| ClinicalTrials.gov Identifier: NCT05480865 |
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Recruitment Status :
Recruiting
First Posted : July 29, 2022
Last Update Posted : February 1, 2024
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Sponsor:
Navire Pharma Inc., a BridgeBio company
Collaborator:
Amgen
Information provided by (Responsible Party):
Navire Pharma Inc., a BridgeBio company
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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 |
|---|---|---|
| Solid Tumor, Adult Metastatic Solid Tumor Metastatic NSCLC Non Small Cell Lung Cancer | Drug: BBP-398 Drug: sotorasib | Phase 1 |
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 Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 85 participants |
| Allocation: | Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Phase 1 Study of the SHP2 Inhibitor BBP-398 (Formerly Known as IACS-15509) in Combination With the KRAS-G12C Inhibitor Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation |
| Actual Study Start Date : | July 6, 2022 |
| Estimated Primary Completion Date : | June 2024 |
| Estimated Study Completion Date : | June 2025 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
Drug Information
available for:
Sotorasib
| Arm | Intervention/treatment |
|---|---|
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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
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Drug: BBP-398
BBP-398 administered orally Drug: sotorasib sotorasib administered orally |
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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
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Drug: BBP-398
BBP-398 administered orally Drug: sotorasib sotorasib administered orally |
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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
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Drug: BBP-398
BBP-398 administered orally Drug: sotorasib sotorasib administered orally |
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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
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Drug: BBP-398
BBP-398 administered orally Drug: sotorasib sotorasib administered orally |
Primary Outcome Measures :
- Phase 1a Dose Escalation Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, Serious Adverse Events, and Dose Limiting Toxicities [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 8 weeks ]Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1
- Duration of response [ Time Frame: 8 weeks ]Defined by RECIST v1.1
- Progression Free Survival (PFS) [ Time Frame: 8 weeks ]Time from treatment start to progression of disease or death by any cause
- Overall survival (OS) [ Time Frame: 8 weeks ]Time from treatment start to death
- Maximum Observed Plasma Concentration (Cmax) of BBP-398 [ Time Frame: Cycle 2 Day 1 ]Maximum plasma concentration of BBP-398 in combination with sotorasib
- Time to Cmax (Tmax) of BBP-398 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Cycle 2 Day 1 ]Terminal half-life of BBP-398 in combination with sotorasib
- Observed Maximum Plasma Concentration (Cmax) of sotorasib [ Time Frame: Cycle 2 Day 1 ]Maximum plasma concentration of sotorasib in combination with BBP-398
- Time to Cmax (Tmax) of sotorasib [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 24 months ]Raw, normalized, and/or baseline adjusted analyte signal
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05480865
Contacts
| Contact: Navire Clinical Operations | 650-391-9740 | NAV1003ct.gov@bridgebio.com |
Locations
Show 25 study locations
Sponsors and Collaborators
Navire Pharma Inc., a BridgeBio company
Amgen
| Responsible Party: | Navire Pharma Inc., a BridgeBio company |
| ClinicalTrials.gov Identifier: | NCT05480865 |
| Other Study ID Numbers: |
NAV-1003 |
| First Posted: | July 29, 2022 Key Record Dates |
| Last Update Posted: | February 1, 2024 |
| Last Verified: | January 2024 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
Keywords provided by Navire Pharma Inc., a BridgeBio company:
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KRAS-G12C mutation SHP2 MAPK-pathway alterations NSCLC |
Additional relevant MeSH terms:
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Neoplasms Sotorasib Immune Checkpoint Inhibitors |
Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Immunological Antineoplastic Agents |