Osimertinib Combined With Anlotinib in EGFR T790M Mutated NSCLC Patients With Progression on Osimertinib Treatment

Phase 2

Terminated

• Conditions: Non Small Cell Lung Cancer
• Interventions: Drug: osimertinib mesylate tablets and anlotinib hydrochloride capsules

• Registration Number: NCT04438902
• Lead Sponsor: First Affiliated Hospital of Zhejiang University

Brief Summary

EGFR T790M gatekeeper mutation accounts for approximately 60% of acquired resistance to the first- or second-generation EGFR-TKI treatment. Osimertinib, a third-generation EGFR TKI, has become the standard therapy for NSCLC patients with acquired EGFR T790M mutation. However, acquired resistance to osimertinib is still inevitable and there is no established targetable agent currently. Thus, treatment strategy for patients with acquire resistance to osimertinib remains an urgent issue. In this study, we aimed to evaluate the efficacy of osimertinib combined with anlotinib in acquired EGFR T790M mutated NSCLC patients with gradual progression on osimertinib treatment.

Detailed Description

In current clinical practice, acquired resistance to osimertinib can be divided into three clinical modes: dramatic progression, gradual progression and local progression. For patients with gradual progression,there are various clinical explorations，including the continuation of osimertinib with chemotherapy or radiotherapy, osimertinib combined with antiangiogenic agents. In preclinical studies, an overactive vascular endothelial growth factor/vascular endothelial growth factor receptor (VEGF/VEGFR) pathway and tumour angiogenesis plays a crucial role in the resistance to EGFR-TKIs, and the dual targeting of both the VEGF and EGFR pathways may prevent resistance.

Anlotinib (AL3818) is an inhibitor targeting multiple receptor tyrosine kinases involved in tumour progression, especially VEGFR 2/3, PDGFRα/β and c-Kit. We suppose that the combination treatment of osimertinib and anlotinib may ameliorate acquired resistance to osimertinib.This is a multi-center, open, single-arm, exploratory phase 2 trial evaluating osimertinib combined with anlotinib in acquired EGFR T790M mutated NSCLC patients with gradual progression on osimertinib treatment.

Study Timeline

• Study First Submitted: 2020-06-15
• Study First Submitted QC: 2020-06-17
• Study First Posted: 2020-06-19
• Study Start: 2020-12-12
• Status Verified: 2021-06
• Primary Completion: 2022-12-08
• Study Completion: 2023-02-16
• Last Update Submitted: 2023-02-17
• Last Update Posted: 2023-02-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

1. Ability to provide informed consent, complete all study assessments and have complete medical record.
2. Age:18-75 years.
3. Histologically or cytologically confirmed diagnosis of local advanced or metastatic NSCLC.
4. Patients should be confirmed acquired EGFR T790M mutation and received osimertinib as the second line treatment, and they should have the following: (1) benefit from treatment with osimertinib initially ;(2) gradual progression on osimertinib treatment as defined by minor increment of tumor burden (≥10% but <20% in the sum of target lesions).
5. At least one measurable lesion as defined by lesions ≥10mm in long axis according to RECIST 1.1.

Exclusion Criteria

1. Patients who will be or were involved in any other interventional antitumour clinical studies for locally advanced/metastatic NSCLC currently or previously.
2. Small cell lung cancer (including small lung cancer mixed with non-small cell lung cancer).
3. Patients at risk of bleeding.
4. Patients with renal dysfunction.
5. Uncontrolled severe hypertension.
6. Any concomitant condition evaluated by physicians which is not suitable for osimertinib or anlotinib treatment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
osimertinib combined with anlotinib	osimertinib mesylate tablets and anlotinib hydrochloride capsules	-

Primary Outcome Measures

Name	Time	Method
progression-free survival (PFS)	from the date of first dose of osimertinib until the date of disease progression，assessed up to 12 months.	PFS is defined as the time from beginning of osimertinib to disease progression on combination treatment of osimertinib and anlotinib.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	from the date of combination of osimertinib and anlotinib, assessed up to 6 weeks.	Objective Response Rate (ORR), is defined as the percentage of patients with complete response or partial response by investigator assessment as recorded in the CRF, which usually refer to Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 in clinical practice.
Adverse events/Serious adverse events	From signing ICF to 30 days after the end of treatment.	Incidence of Adverse Events (AEs): Incidence, severity and seriousness of adverse events, incidence of serious adverse events (SAEs), which usually be graded by CTCAE v5.0 based on current clinical practice.
Disease Control Rate (DCR)	from the date of combination of osimertinib and anlotinib, assessed up to 6 weeks.	Disease Control Rate (DCR), is defined as the percentage of patients with complete response or partial response or stable disease by investigator assessment as recorded in the CRF, which usually refer to RECIST v1.1 in clinical practice.

Trial Locations

Locations (2)

The First Affiliated Hospital, College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China

The First Affiliated Hospital of Jiaxing College; 🇨🇳 Jiaxing, Zhejiang, China