Tumor, Solid
Conditions
Keywords
Cancer, MAPK-pathway alterations
Brief summary
A first-in-human study to evaluate the safety, tolerability and maximum tolerated dose (MTD) and establish the recommended phase 2 dose (RP2D) of BBP-398, a SHP2 inhibitor, in patients with advanced solid tumors.
Detailed description
The first-in-human (FIH) study of BBP-398 will be an open-label, sequential-cohort, non-randomized, Phase 1/1B study utilizing BOIN dose escalation followed by an expansion phase in patients with MAPK pathway- or RTK-driven advanced solid tumors. The primary objective is to determine safety and tolerability of BBP-398, the MTD and RP2D. The secondary objectives are to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profile, preliminary anti-tumor activity, objective response rate (ORR, complete response + partial response rate) and the duration of response (DoR) of BBP-398. The exploratory objective is to assess predictive biomarkers of response.
Interventions
DRUGBBP-398 (Formerly known as IACS-15509)
oral capsules
Sponsors
Navire Pharma Inc., a BridgeBio company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria * Male and non-pregnant females \>18 years old. * Patients must have a diagnosis of advanced (primary or recurrent) or metastatic solid tumor with MAPK-pathway alterations as assessed by clinically validated and/or FDA-approved molecular diagnostic and no available standard of care or curative therapies (MAPK-pathway alterations include, for example KRASG12C mutant, EGFR-mutant). * Dose expansion only: Patients with specific genomically defined tumor types will be recruited. * Patients must have measurable disease by RECIST v1.1. * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. * Patients must have adequate organ function. * Patients must have the ability to understand and the willingness to sign a written informed consent document prior to the initiation of the study and any study procedures. * Patients must be willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other specified study procedures. Key
Exclusion criteria
* Patients with known active Hepatitis B, Hepatitis C infection, or HIV infection. * Patients with a history of CVA, myocardial infarction or unstable angina within the previous 6 months before starting therapy. * Patients with clinically significant cardiac disease. * Patients with tumors harboring known activating mutations. * Patients with a known additional malignancy that is progressing or requires active treatment. * Patients with known central nervous system (CNS) tumors. * Patients with known active CNS metastases and/or carcinomatous meningitis. * Patients who have previously received a SHP2 inhibitor. * Patients with inability to swallow oral medications or with gastrointestinal illness that would preclude the absorption of an oral agent. * Patients on dialysis. * Patients with a life expectancy of ≤12 weeks after the start of IP according to the investigator's judgement. * Patients with known intolerance/hypersensitivity to BBP-398 or its excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determination of Maximum Tolerated Dose (MTD) and establish the RP2D of BBP-398. | Completion of 1 Cycle ( 28 days) | The MTD will be based on DLT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determination of anti-tumor activity of BBP-398 | After 1 dose of BBP-398 | Anti-tumor activity will be defined by objective response rate (ORR2, complete response + partial response rate) and duration of response (DOR3) |
| Maximum observed plasma concentration (Cmax) of BBP-398 | Approximately 6 weeks | Maximum plasma concentration of BBP-398 after single and multiple dose administration of BBP-398 |
| Time to reach Cmax (Tmax) of BBP-398 | Approximately 6 weeks | The amount of time to reach Cmax after single and multiple dose administration of BBP-398 |
| Terminal half-life (t1/2) of BBP-398 | Approximately 6 weeks | Terminal half-life (t1/2) after single and multiple dose administration of BBP-398 |
| Area under the plasma concentration-time curve (AUC) of BBP-398 | Approximately 6 weeks | Area under the plasma concentration versus time curve after single and multiple dose administration of BBP-398 |
Countries
United States
Outcome results
None listed