Business decision

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.

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.

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.