Solid Tumor, AdultPhase 1ArgonautNCT05480865
SHP2 Inhibitor BBP-398 in Combination With Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation
A Phase 1 study testing BBP-398 and sotorasib in people with Solid Tumor, Adult and Metastatic Solid Tumor, run by Navire Pharma Inc., a BridgeBio company at 25 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Solid Tumor, Adult, Metastatic Solid Tumor, Metastatic NSCLC
- What is being tested?
- BBP-398 and sotorasib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 25 sitesin 7 countries
- Study dates
- 6 Jul 2022to 22 Aug 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
25 sites in 7 countries.
25 sites in 7 countries
Australia6 sites
Cancer Research SA
Adelaide, South Australia, 5000
Southern Oncology Clinical Research Unit
Adelaide, South Australia, 5042
Peninsula & South Eastern Haematology and Oncology Group
Frankston, Victoria, 3199
Orange Health Service
Orange, NSW 2800
One Clinical Research
Perth, Western Australia, 6009
St John of God Subiaco Hospital
Subiaco, Western Australia, 6008
Spain6 sites
Quiron Salud Barcelona
Barcelona, 08023
Vall d'Heborn University Hospital - VHIO
Barcelona, 08035
Clinica Universidad de Navarra
Madrid, 28027
Quiron Salud Madrid
Madrid, 28223
Virgen De La Victoria
Málaga, 29010
Hospital Universitario Virgen De La Macarena
Seville
France5 sites
Institute Bergonie
Bordeaux, 33076
Centre Georges François Leclerc
Dijon, 21079
CHU Grenobles Aples
Grenoble, 38043 CEDEX9
Hopital Bichat-Claude Bernard
Paris, 75018
CHU de Rennes - Hôpital Pontchaillou
Rennes, 35000
Italy4 sites
Spedali Civili - Brescia
Brescia, 25123
Careggi University Hospital
Florence, Largo Brambilla, 50134
Istituto Nazionale Tumori (INT) "Fondazione G. Pascale"
Naples, 80131
U.O.C Oncoematologia AOU "Luigi Vanvitelli"
Naples, 80131
Netherlands2 sites
Het Nederlands Kanker Instituut - Antoni van Leewenhoek Ziekenhuis
Amsterdam, 1066 CX
Erasmus Medical Center
Rotterdam, 3000 CA
About this study
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
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.
Read the 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.
- Being tested
- BBP-398, sotorasib
- Keywords
- KRAS-G12C mutation, SHP2, MAPK-pathway alterations, NSCLC
- Medical subject headings
- Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BBP-398Drug
BBP-398 administered orally
sotorasibDrug
sotorasib administered orally
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation: BBP-398 Level 1 and sotorasib | Experimental | 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 Receives: Drug: BBP-398; Drug: sotorasib |
| Dose Escalation: BBP-398 Level 2 and sotorasib | Experimental | 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 Receives: Drug: BBP-398; Drug: sotorasib |
| Dose Escalation: BBP-398 Level 3 and sotorasib | Experimental | 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 Receives: Drug: BBP-398; Drug: sotorasib |
| Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib | Experimental | 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 Receives: Drug: BBP-398; Drug: sotorasib |
| Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib | Experimental | 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 Receives: Drug: BBP-398; Drug: sotorasib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1a Dose Escalation Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, Serious Adverse Events, and Dose Limiting Toxicities
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
Measured: Completion of 1 Cycle (28 days)
Phase 1b Dose Expansion/Optimization Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, and Serious Adverse Events
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
Measured: Completion of 1 Cycle (28 days)
Phase 1b Dose Expansion/Optimization Primary Objective: Overall Response Rate (ORR)
Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1
Measured: 8 weeks
Secondary outcomes (13)
Phase 1a Dose Escalation Secondary Objectives: Overall Response Rate (ORR)
Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1
Measured: 8 weeks
Duration of response
Defined by RECIST v1.1
Measured: 8 weeks
Progression Free Survival (PFS)
Time from treatment start to progression of disease or death by any cause
Measured: 8 weeks
Overall survival (OS)
Time from treatment start to death
Measured: 8 weeks
Maximum Observed Plasma Concentration (Cmax) of BBP-398
Maximum plasma concentration of BBP-398 in combination with sotorasib
Measured: Cycle 2 Day 1
Time to Cmax (Tmax) of BBP-398
Amount of time to reach Cmax of BBP-398 in combination with sotorasib
Measured: Cycle 2 Day 1
Area under the plasma concentration-time curve (AUC) of BBP-398
Area under the plasma concentration versus time curve of BBP-398 in combination with sotorasib
Measured: Cycle 2 Day 1
Half-life (T1/2) of BBP-398
Terminal half-life of BBP-398 in combination with sotorasib
Measured: Cycle 2 Day 1
Observed Maximum Plasma Concentration (Cmax) of sotorasib
Maximum plasma concentration of sotorasib in combination with BBP-398
Measured: Cycle 2 Day 1
Time to Cmax (Tmax) of sotorasib
Amount of time to reach Cmax of sotorasib in combination with BBP-398
Measured: Cycle 2 Day 1
Area under the plasma concentration-time curve (AUC) over dosing interval of sotorasib
Area under the plasma concentration versus time curve of sotorasib in combination with BBP-398
Measured: Cycle 2 Day 1
Half-life (T1/2) of sotorasib
Terminal half-life of sotorasib in combination with BBP-398
Measured: Cycle 2 Day 1
Circulating and intratumoral target engagement biomarkers of BBP-398 activity in combination with sotorasib
Raw, normalized, and/or baseline adjusted analyte signal
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2022
- Study start6 Jul 2022
- Primary completion22 Aug 2024
- Study completion22 Aug 2024
Why it stopped: Business Reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Navire Pharma Inc., a BridgeBio company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Amgen
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05480865
- Sponsor's protocol ID
- NAV-1003
- Acronym
- Argonaut
- Status last verified
- Dec 2024
- First submitted
- 15 Jul 2022
- Last updated
- 12 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05480865
- Acronym / sponsor ID
- Argonaut / NAV-1003
- Keywords
- KRAS-G12C mutation, SHP2, MAPK-pathway alterations, NSCLC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Reasons
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Navire Pharma Inc., a BridgeBio companyIndustry (pharma, biotech, devices)
- Collaborators
- Amgen
- Study start
- 6 Jul 2022 (actual)
- Primary completion
- 22 Aug 2024 (actual)
- Study completion
- 22 Aug 2024 (actual)
- First posted
- 29 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation: BBP-398 Level 1 and sotorasib | Experimental | Drug: BBP-398, Drug: sotorasibBBP-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 | Experimental | Drug: BBP-398, Drug: sotorasibBBP-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 | Experimental | Drug: BBP-398, Drug: sotorasibBBP-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 | Experimental | Drug: BBP-398, Drug: sotorasibBBP-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 | Experimental | Drug: BBP-398, Drug: sotorasibBBP-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 |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BBP-398BBP-398 administered orally | Drug | Dose Escalation: BBP-398 Level 1 and sotorasib, Dose Escalation: BBP-398 Level 2 and sotorasib, Dose Escalation: BBP-398 Level 3 and sotorasib, Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib, Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib |
| sotorasibsotorasib administered orally | Drug | Dose Escalation: BBP-398 Level 1 and sotorasib, Dose Escalation: BBP-398 Level 2 and sotorasib, Dose Escalation: BBP-398 Level 3 and sotorasib, Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib, Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib |
Primary outcome
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
13 secondary outcomes
Phase 1a Dose Escalation Secondary Objectives: Overall Response Rate (ORR)
Time frame: 8 weeks
Duration of response
Time frame: 8 weeks
Progression Free Survival (PFS)
Time frame: 8 weeks
Overall survival (OS)
Time frame: 8 weeks
Maximum Observed Plasma Concentration (Cmax) of BBP-398
Time frame: Cycle 2 Day 1
Time to Cmax (Tmax) of BBP-398
Time frame: Cycle 2 Day 1
Area under the plasma concentration-time curve (AUC) of BBP-398
Time frame: Cycle 2 Day 1
Half-life (T1/2) of BBP-398
Time frame: Cycle 2 Day 1
Observed Maximum Plasma Concentration (Cmax) of sotorasib
Time frame: Cycle 2 Day 1
Time to Cmax (Tmax) of sotorasib
Time frame: Cycle 2 Day 1
Area under the plasma concentration-time curve (AUC) over dosing interval of sotorasib
Time frame: Cycle 2 Day 1
Half-life (T1/2) of sotorasib
Time frame: Cycle 2 Day 1
Circulating and intratumoral target engagement biomarkers of BBP-398 activity in combination with sotorasib
Time frame: 24 months
Results and safety
The study was stopped early (reason given: Business Reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BBP-398 and sotorasib in people with Solid Tumor, Adult and Metastatic Solid Tumor, run by Navire Pharma Inc., a BridgeBio company at 25 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in Australia, Spain, France, Italy, Netherlands and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Business Reasons). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Dec 2024.