NCT04770688

Advanced Lung Tumor Treated by Osimertinib Plus Anlotinib

Safety and Efficacy of Osimertinib Combined With Anlotinib in EGFRm+, Treatment-naïve IIIb/IV NSCLC Patients: a Prospective, Single Arm, Phase Ib/IIa Study

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Shanghai Chest Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a prospective, single arm, phase Ib/IIa study. Up to 25 patients will be enrolled into the study (Part A: 2-18; Part B: 7-19). The study has been designed to allow an investigation of the optimal combination dose and schedule whilst of Osimertinib plus Anlotinib in patients with EGFRm+, treatment-naïve IIIb/IV Non-Small Cell Lung Cancer (NSCLC) ensuring the safety of patients with intensive safety monitoring. There are two main parts to this study; Part A, Combination dose finding and Parts B, Dose expansion.

Detailed description

Part A has been designed to identify the recommended dose of the combination of Osimertinib plus Anlotinib for further clinical evaluation based upon assessment of the safety and tolerability data collected during the first 21 days (cycle 1, 21 days per cycle). A cycle of study treatment will be defined as 21 days. Dosing will begin at Osimertinib 80mg QD continuously and Anlotinib 8mg QD from day1 to 14 of a 21-day cycle. In the first 6 patients, a delay of at least 21 days (the first group of 3 patients) and a delay of at least 7 days (the second group of 3 patients) will be mandatory between the administration of the first dose to the first patient and administration of first dose to subsequent patients. Patients will be enrolled to ensure a minimum of 3 and a maximum of 6 evaluable patients per cohort. Dose escalation and de-escalation will follow the scheme below, according to the following logic：If no dose-limiting toxicity (DLT) is observed (for definition see Section 4.1.3) in a cohort of 3 evaluable patients then dose escalation may occur. Dose increases will be permitted after review of data from a minimum of 3 evaluable patients has been performed. * If one patient experiences a DLT in a group of 3 evaluable patients then the cohort will be expanded to include 6 evaluable patients. If only one DLT is observed in the complete cohort of 6 evaluable patients then dose escalation may occur. * If 2 or more patients experience a DLT in a group of up to 6 patients, irrespective of the number of patients enrolled, the dose will be considered not tolerated and recruitment to the cohort and dose escalation will cease. Safety will be intensively monitored in part A. If RP2D was not reached in Part A, Part B would not be initiated. If RP2D was reached in Part A, eligible patients in part B will be enrolled and receive Osimertinib (80mg QD, continuously) plus Anlotinib (RP2D, QD from day 1 to 14 of a 21-day cycle) till disease progression (PD) or unacceptable toxicity, with the aim to further evaluate the safety, tolerability and efficacy in terms of ORR, DCR, DOR, PFS, overall survival at 12 months. For all eligible patients (Part A and Part B), tissue and/or blood samples at baseline and PD will be collected to understand the resistance profile.

Conditions

• Non-Small Cell Lung Cancer With EGFR Mutation
• Locally Advanced Solid Tumor
• Metastatic Cancer
• Adenocarcinoma of Lung

Interventions

Type	Name	Description
DRUG	Osimertinib	Osimertinib, 80mg, QD, p.o.
DRUG	Anlotinib	(Phase Ib) Anlotinib, from 8mg to10mg to 12mg, QD, p.o. from day 1 to 14 of a 21-day cycle. (Phase IIa)Anlotinib, given at RP2D dose QD, p.o. from day 1 to 14 of a 21-day cycle.

Timeline

• Start date: 2020-11-19
• Primary completion: 2024-06-20
• Completion: 2024-06-20
• First posted: 2021-02-25
• Last updated: 2024-08-15

Locations

1 site across 1 country: China