NCT04862780

(SYMPHONY) Phase 1/2 Study Targeting EGFR Resistance Mechanisms in NSCLC

A Phase 1/2 Study Targeting Acquired Resistance Mechanisms in Patients With EGFR Mutant Non-Small Cell Lung Cancer

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 177 (actual)
• Sponsor: Blueprint Medicines Corporation · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1/2, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and anticancer activity of BLU-945, a selective EGFR inhibitor, as monotherapy or in combination with osimertinib.

Detailed description

The study will include an initial Phase 1 portion to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BLU-945 as monotherapy (initially in a QD regimen with the option to evaluate BID dosing, if supported by emerging PK and safety data), as well as an additional dose-escalation portion to determine the RP2D of BLU-945 in combination with osimertinib. The BLU-945 monotherapy Phase 2 expansion groups will consist of patients with tumors harboring specific mutation profiles (EGFR T790M and C797S mutation \[Group 1\]; EGFR T790M but not C797S \[Group 2\]; or EGFR C797S but not T790M \[Group 3\]). The BLU-945 with osimertinib Phase 2 expansion (Group 4) will include approximately 24 evaluable patients, with at least 12 slots reserved for patients with EGFR T790M and C797S mutation.

Conditions

• Lung Neoplasms
• Carcinoma, Non-Small-Cell Lung
• Respiratory Tract Neoplasms
• Neoplasms
• Neoplasms by Site
• Lung Diseases
• Respiratory Tract Disease
• Carcinoma, Bronchogenic
• Bronchial Neoplasms
• Adenocarcinoma
• Carcinoma
• Neoplasms by Histologic Type
• Neoplasms, Nerve Tissue
• EGFR T790M
• EGFR C797S
• EGFR L858R
• EGFR Gene Mutation
• EGF-R Positive Non-Small Cell Lung Cancer
• EGFR Exon 19 Deletion
• EGFR Mutation Resulting in Tyrosine Kinase Inhibitor Resistance
• EGFR Activating Mutation
• Protein Kinase Inhibitors
• Antineoplastic Agents
• Thoracic Neoplasms

Interventions

Type	Name	Description
DRUG	BLU-945	Oral administration
DRUG	osimertinib	Osimertinib tablets for oral administration

Timeline

• Start date: 2021-06-29
• Primary completion: 2024-10-07
• Completion: 2024-10-07
• First posted: 2021-04-28
• Last updated: 2025-02-10

Locations

26 sites across 10 countries: United States, Canada, France, Japan, Netherlands, Singapore, South Korea, Spain, Taiwan, United Kingdom

Regulatory

• FDA-regulated drug study