SHP2 Inhibitor BBP-398 in Combination With Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation

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.

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.

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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.