Non Small Cell Lung CancerPhase 1NCT05375084
SHP2 Inhibitor BBP-398 in Combination With Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer With a KRAS Mutation
A Phase 1 study testing BBP-398 with nivolumab in people with Non Small Cell Lung Cancer and Solid Tumor, run by Navire Pharma Inc., a BridgeBio company at 15 sites in United States.
Trial summary
This is a Phase 1 study of BBP-398, a SHP2 inhibitor, in combination with nivolumab, a PD-1 antibody, in patients with NSCLC with a KRAS mutation. The study involves 2 parts: Phase 1a Dose Escalation and Phase 1b Dose Expansion. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer, Solid Tumor
- What is being tested?
- BBP-398 with nivolumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 15 sitesUnited States
- Study dates
- 20 Oct 2022to 15 Jul 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 years and older
- 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 NSCLC with documentation of a KRAS mutation within the 1 year 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 at least one prior line of systemic therapy, which must include platinum-based doublet chemotherapy and anti-PD-(L)1 therapy.
- Patients must have experienced progressive or recurrent disease occurring either during treatment or within 90 days after discontinuing anti-PD-(L)1 therapy.
- 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 known central nervous system (CNS) tumors or active CNS metastases.
- Patients that have experienced progressive disease (PD) within the first 120 days of initiating treatment with an anti- PD-(L)1 agent (e.g., primary refractory).
- Patients that have a history of allogenic bone marrow transplant.
- Patients that have select known or suspected autoimmune disease.
- Patients that have a condition requiring systemic treatment with either corticosteroids (>10 mg prednisone equivalent) or other immunosuppressive medication within 14 days of study start.
- Patients that have received any live/attenuated vaccine within 30 days of first study treatment.
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
United States15 sites
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21224
Roswell Park Cancer Institute
Buffalo, New York, 14203
Medical University of South Carolina (MUSC) - Hollings Cancer Center
Charleston, South Carolina, 29425
Cleveland Clinic
Cleveland, Ohio, 44195
Henry Ford Hospital
Detroit, Michigan, 48202
NEXT Oncology
Fairfax, Virginia, 22031
Memorial Regional Hospital (Memorial Cancer Institute)
Hollywood, Florida, 33021
MD Anderson Cancer Center
Houston, Texas, 77030
Millennium Research and Clinical Development
Houston, Texas, 77090
Scripps Clinic Torrey Pines
La Jolla, California, 92037
University of Pennsylvania (Abramson Cancer Center)
Philadelphia, Pennsylvania, 19104
Providence Portland Medical Center
Portland, Oregon, 97213
Providence Medical Foundation
Santa Rosa, California, 95403
Highlands Oncology
Springdale, Arkansas, 72762
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: A Phase 1 Study of the SHP2 Inhibitor BBP-398 (Formerly Known as IACS-15509) in Combination With the Programmed Death Receptor-1 Blocking Antibody Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer With a KRAS Mutation
This is a Phase 1 study of BBP-398, a SHP2 inhibitor, in combination with nivolumab, a PD-1 antibody, in patients with NSCLC with a KRAS mutation. The study involves 2 parts: Phase 1a Dose Escalation and Phase 1b Dose Expansion.
Read the detailed description
The primary objective for Phase 1a Dose Escalation is to evaluate the safety, tolerability, and RP2D of BBP-398, a SHP2 inhibitor, when used in combination with nivolumab in patients with advanced NSCLC with a KRAS mutation who have failed standard of care treatment.
The primary objective for Phase 1b Dose Expansion is to evaluate the antitumor activity of BBP-398, as defined by the ORR (per investigator) according to RECIST v1.1, when used in combination with nivolumab in patients with advanced NSCLC with a KRAS mutation who have failed standard of care treatment.
- Conditions
- Non Small Cell Lung Cancer, Solid Tumor
- Being tested
- BBP-398 with nivolumab
- Keywords
- KRAS mutation, MAPK-pathway alterations, NSCLC, SHP2
- Medical subject headings
- 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-398 with nivolumabDrug
BBP-398 administered orally once a day (QD); nivolumab administered intravenously every 4 weeks (Q4wks)
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Level 1 | Experimental | Level 1 oral capsules administered in combination with nivolumab Receives: Drug: BBP-398 with nivolumab |
| Dose Escalation Level 2 | Experimental | Level 2 oral capsules administered in combination with nivolumab Receives: Drug: BBP-398 with nivolumab |
| Dose Escalation Level 3 | Experimental | Level 3 oral capsules administered in combination with nivolumab Receives: Drug: BBP-398 with nivolumab |
| Dose Expansion | Experimental | RP2D defined dose. Oral capsules administered in combination with nivolumab Receives: Drug: BBP-398 with nivolumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1a Dose Escalation: Assess safety, tolerability, and recommended phase 2 dose (RP2D) of BBP-398 in combination with nivolumab
Measured: Completion of 1 Cycle (28 days)
Phase 1b Dose Expansion: Assess antitumor activity of BBP-398 in combination with nivolumab
Anti-tumor activity will be defined by objective response rate (ORR) according to RECIST v1.1
Measured: Completion of 1 Cycle (28 days)
Secondary outcomes (2)
Assess preliminary antitumor activity of BBP-398 in combination with nivolumab
Anti-tumor activity will be defined by objective response rate (ORR) [escalation], duration of response (DOR) and progression free survival (PFS), as defined by RECIST v1.1. and overall survival (OS) [both escalation and expansion]
Measured: Completion of 1 Cycle (28 days)
Phase 1b Dose Expansion: Assess safety and tolerability of BBP-398 at the RP2D, in combination with nivolumab
Measured: Completion of 1 Cycle (28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2022
- Study start20 Oct 2022
- Primary completion12 Apr 2024
- Study completion15 Jul 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 Non Small Cell Lung CancerStudies 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Navire Pharma Inc., a BridgeBio company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05375084
- Sponsor's protocol ID
- NAV-1004
- Status last verified
- Dec 2024
- First submitted
- 10 May 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 Programmed Death Receptor-1 Blocking Antibody Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer With a KRAS Mutation
- ClinicalTrials.gov ID
- NCT05375084
- Acronym / sponsor ID
- NAV-1004
- Conditions
- Non Small Cell Lung Cancer, Solid Tumor
- Keywords
- KRAS mutation, MAPK-pathway alterations, NSCLC, SHP2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business reasons
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Navire Pharma Inc., a BridgeBio companyIndustry (pharma, biotech, devices)
- Collaborators
- Bristol-Myers Squibb
- Study start
- 20 Oct 2022 (actual)
- Primary completion
- 12 Apr 2024 (actual)
- Study completion
- 15 Jul 2024 (actual)
- First posted
- 16 May 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 nivolumab, a PD-1 antibody, in patients with NSCLC with a KRAS mutation. The study involves 2 parts: Phase 1a Dose Escalation and Phase 1b Dose Expansion.
Detailed description
The primary objective for Phase 1a Dose Escalation is to evaluate the safety, tolerability, and RP2D of BBP-398, a SHP2 inhibitor, when used in combination with nivolumab in patients with advanced NSCLC with a KRAS mutation who have failed standard of care treatment.
The primary objective for Phase 1b Dose Expansion is to evaluate the antitumor activity of BBP-398, as defined by the ORR (per investigator) according to RECIST v1.1, when used in combination with nivolumab in patients with advanced NSCLC with a KRAS mutation who have failed standard of care treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dose Escalation Level 1 | Experimental | Drug: BBP-398 with nivolumabLevel 1 oral capsules administered in combination with nivolumab |
| Dose Escalation Level 2 | Experimental | Drug: BBP-398 with nivolumabLevel 2 oral capsules administered in combination with nivolumab |
| Dose Escalation Level 3 | Experimental | Drug: BBP-398 with nivolumabLevel 3 oral capsules administered in combination with nivolumab |
| Dose Expansion | Experimental | Drug: BBP-398 with nivolumabRP2D defined dose. Oral capsules administered in combination with nivolumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients must have histologically documented, locally advanced and unresectable, or metastatic NSCLC with documentation of a KRAS mutation within the 1 year 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 at least one prior line of systemic therapy, which must include platinum-based doublet chemotherapy and anti-PD-(L)1 therapy.
- Patients must have experienced progressive or recurrent disease occurring either during treatment or within 90 days after discontinuing anti-PD-(L)1 therapy.
Key exclusion criteria (8 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 known central nervous system (CNS) tumors or active CNS metastases.
- Patients that have experienced progressive disease (PD) within the first 120 days of initiating treatment with an anti- PD-(L)1 agent (e.g., primary refractory).
- 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-398 with nivolumabBBP-398 administered orally once a day (QD); nivolumab administered intravenously every 4 weeks (Q4wks) | Drug | Dose Escalation Level 1, Dose Escalation Level 2, Dose Escalation Level 3, Dose Expansion |
Primary outcome
Phase 1a Dose Escalation: Assess safety, tolerability, and recommended phase 2 dose (RP2D) of BBP-398 in combination with nivolumab
Time frame: Completion of 1 Cycle (28 days)
Phase 1b Dose Expansion: Assess antitumor activity of BBP-398 in combination with nivolumab
Time frame: Completion of 1 Cycle (28 days)
Anti-tumor activity will be defined by objective response rate (ORR) according to RECIST v1.1
2 secondary outcomes
Assess preliminary antitumor activity of BBP-398 in combination with nivolumab
Time frame: Completion of 1 Cycle (28 days)
Phase 1b Dose Expansion: Assess safety and tolerability of BBP-398 at the RP2D, in combination with nivolumab
Time frame: Completion of 1 Cycle (28 days)
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.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BBP-398 with nivolumab in people with Non Small Cell Lung Cancer and Solid Tumor, run by Navire Pharma Inc., a BridgeBio company at 15 sites in United States.
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 7 inclusion and 8 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 15 sites in United States. 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: Assess safety, tolerability, and recommended phase 2 dose (RP2D) of BBP-398 in combination with nivolumab (time frame: Completion of 1 Cycle (28 days)). The study lists 2 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.