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

• ClinicalTrials.gov Identifier: NCT04438902
• Recruitment Status: Not yet recruiting
• First Posted: June 19, 2020
• Last Update Posted: June 19, 2020
• Sponsor: First Affiliated Hospital of Zhejiang University
• Information provided by (Responsible Party): First Affiliated Hospital of Zhejiang University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Non Small Cell Lung Cancer	Drug: osimertinib mesylate tablets and anlotinib hydrochloride capsules	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This is a multi-center, open, single-arm, exploratory phase 2 trial.
• Masking: None (Open Label)
• Primary Purpose: 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
• Estimated Study Start Date: June 2020
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: osimertinib combined with anlotinib	Drug: osimertinib mesylate tablets and anlotinib hydrochloride capsules; osimertinib mesylate tablets 80mg qd and anlotinib hydrochloride capsules 10mg qd day 1-14 of a 21-day cycle; Other Name: TAGRISSO and FOCUS V

Outcome Measures

Primary Outcome Measures :

1. progression-free survival (PFS) [ Time Frame: 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 :

1. Objective Response Rate (ORR) [ Time Frame: 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.
2. Disease Control Rate (DCR) [ Time Frame: 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.
3. Adverse events/Serious adverse events [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Yuehong Wang; 13989826233; yuehongw@zju.edu.cn

Contact: Shan Lu; 137 5822 2639

Locations

China, Zhejiang

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, Zhejiang, China, 310003

Contact: Yuehong Wang, MD 13989826233 yuehongw@zju.edu.cn

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China, 310014

Contact: Liqin Lu 13858039628

The First Affiliated Hospital of Jiaxing College

Jiaxing, Zhejiang, China, 314001

Contact: Qi Zhang 13957382862

Sponsors and Collaborators

First Affiliated Hospital of Zhejiang University

Investigators

• Principal Investigator: Yuehong Wang; First Affiliated Hospital of Zhejiang University

More Information

• Responsible Party: First Affiliated Hospital of Zhejiang University
• ClinicalTrials.gov Identifier: NCT04438902
• Other Study ID Numbers: TRAIN
• First Posted: June 19, 2020
• Last Update Posted: June 19, 2020
• Last Verified: June 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No plan to share participant data of the trial.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by First Affiliated Hospital of Zhejiang University:

non-small-cell lung cancer; EGFR T790M; osimertinib; anlotinib; acquired resistance

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Osimertinib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action