Clinical trial NCT04438902: Osimertinib Combined With Anlotinib in EGFR T790M Mutated NSCLC Patients With Progression on Osimertinib Treatment
Official title: A Prospective, Multi-center, Interventional Study of Osimertinib Combined With Anlotinib in Acquired EGFR T790M Mutated NSCLC Patients With Gradual Progression on Osimertinib Treatment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Non Small Cell Lung Cancer
Keywords: non-small-cell lung cancer
EGFR T790M
osimertinib
anlotinib
acquired resistance
Lead sponsor: First Affiliated Hospital of Zhejiang University
Sponsor class: OTHER
First posted: 2020-06-19
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a multi-center, open, single-arm, exploratory phase 2 trial.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: progression-free survival (PFS)
timeFrame: from the date of first dose of osimertinib until the date of disease progression，assessed up to 12 months.
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: from the date of combination of osimertinib and anlotinib, assessed up to 6 weeks.
measure: Disease Control Rate (DCR)
timeFrame: from the date of combination of osimertinib and anlotinib, assessed up to 6 weeks.
measure: Adverse events/Serious adverse events
timeFrame: From signing ICF to 30 days after the end of treatment.
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital, College of Medicine, Zhejiang University
state: Zhejiang
city: Jiaxing
country: China
facility: The First Affiliated Hospital of Jiaxing College
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Zhejiang University
name: Yuehong Wang
role: PRINCIPAL_INVESTIGATOR
References: