NCT05497076

the Efficacy and Safety of Dalpiciclib Combined With Third-generation EGFR-TKI in Patients With EGFR Mutation and Meningial Metastasis in Non-small Cell Lung Cancer Progressing Through Third-generation TKI and Platinum-containing Two-drug Chemotherapy

A Single-center, Single-arm, Phase Ib Clinical Study of the Efficacy and Safety of Dalpiciclib Combined With Third-generation EGFR-TKI in Patients With EGFR Mutation and Meningial Metastasis in Non-small Cell Lung Cancer Progressing Through Third-generation TKI and Platinum-containing Two-drug Chemotherapy

• Status: Unknown
• Phase: —
• Study type: Observational
• Enrollment: 9 (estimated)
• Sponsor: Fujian Cancer Hospital · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Efficacy and safety of Dalpiciclib combined with third-generation EGFR-TKI in patients with advanced EGFR-mutated non-small cell lung cancer with meningeal metastasis after third-generation TKI and platinum-containing chemotherapy

Detailed description

Subjects with advanced NSCLC who developed meningeal progression after previous platinum-based two-drug chemotherapy and third-generation EGFR-TKI treatment were enrolled. Exploratory analysis: Peripheral blood and/or cerebrospinal fluid samples were retained before medication, 4 weeks after medication, and after progression. Cdk4/6, CDKN2A, CDKN2B, CCND1 (Cyclin D1), CCND2 (Cyclin D2) and CCND3 (Cyclin D2) were detected by NGS D3), CCNE1, RB1 cell cycle pathway changes and subjects without these changes in stratification, namely whether the above cell cycle regulation abnormalities can be used as biomarkers for efficacy prediction and prognosis. And whether there are differences in the expression of the above genes in peripheral blood and cerebrospinal fluid, to explore the relationship between intracranial and extracranial cell cycle regulation abnormalities in the upstream and downstream pathways. The first stage was the safety introduction period, in which the previous drugs and fixed doses of the third generation EGFR-TKI were continued, and Dalpiciclib was enrolled in the 3+3 mode. After one subject was enrolled, the second subject was enrolled after completing the dose-limiting toxicity (DLT) observation period (3 weeks). If no DLT was found in the 3 subjects, the next dose ramp could be performed. If there was 1 DLT, 3 patients of this dose grade were added to the group. If no DLT was found in any of the 3 cases, the next dose grade was entered. It is planned to enroll 6 to 9 subjects. According to the safety data obtained during the safety observation period, it will be determined whether to add other dose groups for exploration in the first stage after comprehensive analysis and discussion.

Conditions

• Non-small Cell Lung Cancer Confirmed by Histopathology or Cytology
• The TNM (8th) Phase is IV
• With EGFR Mutations
• Meningeal Progression Occurred After Previous Platinum-containing Two-drug Chemotherapy and Third-generation EGFR-TKI Treatment
• Male or Female
• The Age of 18 Years Old or More
• ECOG PS 0 to 2 Points

Timeline

• Start date: 2022-09-01
• Primary completion: 2024-01-01
• Completion: 2024-07-01
• First posted: 2022-08-11
• Last updated: 2022-08-11