Clinical trial NCT04528836: First-in-Human Study of the SHP2 Inhibitor BBP-398 in Patients With Advanced Solid Tumors
Official title: A Phase 1/1B First-in-Human Study of the SHP2 Inhibitor BBP-398 (Formerly Known as IACS-15509) in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Tumor, Solid
Keywords: Cancer
MAPK-pathway alterations
Lead sponsor: Navire Pharma Inc., a BridgeBio company
Sponsor class: INDUSTRY
First posted: 2020-08-27
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Determination of Maximum Tolerated Dose (MTD) and establish the RP2D of BBP-398.
timeFrame: Completion of 1 Cycle ( 28 days)
Secondary outcomes:
measure: Determination of anti-tumor activity of BBP-398
timeFrame: After 1 dose of BBP-398
measure: Maximum observed plasma concentration (Cmax) of BBP-398
timeFrame: Approximately 6 weeks
measure: Time to reach Cmax (Tmax) of BBP-398
timeFrame: Approximately 6 weeks
measure: Terminal half-life (t1/2) of BBP-398
timeFrame: Approximately 6 weeks
measure: Area under the plasma concentration-time curve (AUC) of BBP-398
timeFrame: Approximately 6 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: Scripps MD Anderson Cancer Center
state: California
city: Orange
country: United States
facility: UC Irvine Health
state: California
city: Santa Monica
country: United States
facility: UCLA Hematology/Oncology - Santa Monica
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute
state: Colorado
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Tacoma
country: United States
facility: MultiCare Institute for Research & Innovation
state: Washington
Study officials:
References: