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

Phase 1TerminatedNCT05480865

Navire Pharma Inc., a BridgeBio company28 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumor, Adult Metastatic Solid Tumor Metastatic NSCLC Non Small Cell Lung Cancer

Interventions

BBP-398DRUG

BBP-398 administered orally

sotorasibDRUG

sotorasib administered orally

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

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.

Locations (25)

Cancer Research SA

Adelaide, South Australia, Australia

Outcomes

Primary Outcomes

Phase 1a Dose Escalation Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, Serious Adverse Events, and Dose Limiting Toxicities

Number of patients experiencing treatment-emergent adverse events, serious adverse events, including changes in lab parameters, vital signs and electrocardiogram changes; duration, and severity based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Time frame: Completion of 1 Cycle (28 days)

Phase 1b Dose Expansion/Optimization Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, and Serious Adverse Events

Time frame: Completion of 1 Cycle (28 days)

Phase 1b Dose Expansion/Optimization Primary Objective: Overall Response Rate (ORR)

Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1

Time frame: 8 weeks

Secondary Outcomes

Phase 1a Dose Escalation Secondary Objectives: Overall Response Rate (ORR)

Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1

Time frame: 8 weeks

Duration of response

Defined by RECIST v1.1

Time frame: 8 weeks

Progression Free Survival (PFS)

Time from treatment start to progression of disease or death by any cause

Time frame: 8 weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.