Furmonertinib Monotherapy and Combination Therapy in Advanced EGFR Mutant NSCLC With Uncleared ctDNA
FOCUS-C
FurmOnertinib Mesylate With or Without Chemotherapy +/- bevacizUmab as firSt Line Treatment in Advanced Non-small Cell Lung Cancer Patients With Uncleared Epidermal Growth Factor Receptor (EGFR) Mutation Positive Circulating Tumor Cell DNA
1 other identifier
interventional
280
1 country
26
Brief Summary
EGFR mutation positive advanced NSCLC patients with uncleared ctDNA have poor prognosis, whether they can benefit from combination therapy has not been reported. This study aims to investigate the efficacy and safety of combination therapy compared with furmonertinib monotherapy in advanced EGFR mutant NSCLC with uncleared circulating tumor cell DNA.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 nonsmall-cell-lung-cancer
Started May 2022
Longer than P75 for phase_2 nonsmall-cell-lung-cancer
26 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 7, 2022
CompletedFirst Posted
Study publicly available on registry
April 19, 2022
CompletedStudy Start
First participant enrolled
May 6, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 28, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
February 29, 2028
ExpectedAugust 31, 2022
August 1, 2022
2.8 years
April 7, 2022
August 26, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression-free survival (PFS)
Progression-free survival (PFS) using Investigator assessment as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Progression-free survival (PFS) is defined as the time from beginning of study treatment until the date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy prior to progression. Patients who have not progressed or died at the time of analysis will be censored at the time of the latest date of assessment from their last evaluable Response Evaluation Criteria in Solid Tumors (RECIST) assessment.
The primary analysis of Progression-free survival (PFS) based on investigator assessment will occur when PFS maturity is observed at approximately 34 months after the first patient begin study treatment
Secondary Outcomes (6)
Objective Response Rate (ORR)
Analysis will occur when PFS maturity is observed at approximately 34 months from the first patient begin study treatment
Disease Control Rate (DCR)
Analysis will occur when PFS maturity is observed at approximately 34 months from the first patient begin study treatment
Duration of Response (DoR)
Duration of Response analysis will occur when Progression-free survival (PFS) maturity is observed at approximately 34 months from the first patient begin study treatment
Overall Survival (OS)
The analysis of OS will be conducted at 2 time points: when PFS maturity is observed at approximately 34 months after the first patient begin study treatment, and when OS maturity is observed at approximately 70 months after the first patient begin study
Landmark Overall Survival (LOS)
The analysis of Landmark Overall Survival will be conducted at 2 time points: when PFS maturity is observed at approximately 34 months after the first patient begin study treatment, and when Overall Survival maturity is observed at approximately 70 month
- +1 more secondary outcomes
Other Outcomes (2)
Change from baseline and time to deterioration in gene mutation spectrum of ctDNA
Gene mutation spectrum changes based on ctDNA analysis will occur when PFS maturity is observed at approximately 34 months from the first patient begin study treatment
Circulating tumor DNA (ctDNA) clearance rate
The data of ctDNA clearance rate will be collected at 2 time points: 3 weeks following the first dose of study drug in induction treatment, and 3 weeks after randomization
Study Arms (4)
Group A: Furmonertinib 80mg QD
EXPERIMENTALFurmonertinib (AST2818) 80mg QD. All patients enrolled into this group will receive furmonertinib 80mg daily.
Group B1: Furmonertinib 80mg QD
EXPERIMENTALFurmonertinib (AST2818) 80mg QD. All patients enrolled into this group will receive furmonertinib 80mg daily.
Group B2: Furmonertinib plus chemotherapy
EXPERIMENTALFurmonertinib 80 mg QD and platinum-based chemotherapy All patients enrolled into this group will receive furmonertinib 80 mg daily, in combination with Pemetrexed (500 mg/m2) plus carboplatin (AUC 5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by pemetrexed maintenance (500 mg/m2) every 3 weeks.
Group B3: Furmonertinib plus chemotherapy and bevacizumab
EXPERIMENTALFurmonertinib 80 mg QD plus platinum-based chemotherapy and bevacizumab All patients enrolled into this group will receive furmonertinib 80 mg daily, in combination with Pemetrexed (500 mg/m2) plus carboplatin (AUC 5) plus bevacizumab (7.5mg/kg) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by pemetrexed (500 mg/m2) with bevacizumab (7.5mg/kg) maintenance every 3 weeks.
Interventions
Furmonertinib 80mg daily + Pemetrexed (500 mg/m2) plus carboplatin (AUC 5) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by pemetrexed maintenance (500 mg/m2) every 3 weeks.
Furmonertinib 80mg daily + Pemetrexed (500 mg/m2) plus carboplatin (AUC 5) plus bevacizumab (7.5mg/kg) on Day 1 of 21day cycles (every 3 weeks) for 4 cycles, followed by pemetrexed (500 mg/m2) with bevacizumab (7.5mg/kg) maintenance every 3 weeks.
Eligibility Criteria
You may qualify if:
- Provide informed consent prior to any study specific procedures;
- at least 18 years of age;
- ECOG PS of 0 to 1 at screening with no clinically significant deterioration in the previous 2 weeks, life expectancy ≥12 weeks;
- Pathologically confirmed non-squamous Non-Small Cell Lung Cancer (NSCLC);
- Locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy;
- Patient with EGFR 19Del or L858R mutation diagnosed histologically or cytologically and confirmed by ctDNA, the reports must be issued or recognized by Tier 3A hospitals. The mutations above may exist alone or together;
- Patients must have untreated advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy;
- According to RECIST 1.1, patients have at least one tumor lesion at baseline that meets the following requirements: accurately and repeatably measurable at baseline;
- For premenopausal women with childbearing potential, a pregnancy test must be performed within 7 days before the first dose, and the pregnancy test (blood or urine test) must be negative; female subjects must not be lactating;
- Willing to use contraception as appropriate during the study and for a period after discontinuing study treatment;
- Voluntary and agree to follow the study treatment protocol as well as follow-up plan, and can accept the oral medicine treatment;
- Voluntary and agree to sign the informed consent for genetic research, and provide enough fresh blood samples for central NGS testing.
You may not qualify if:
- squamous cell lung carcinoma;
- History of hypersensitivity to active or inactive excipients of investigational product (IP) or drugs with a similar chemical structure or class to investigational product (IP);
- Confirmed EGFR 20 exon insertion mutations at any time after the initial diagnosis;
- Patient who receive prior treatment including any of the following:
- Any Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI);
- The patients who have received intrapleural perfusion therapy can only be enrolled 28 days or more after the pleural effusion is stable;
- Major surgery within 4 weeks of the first dose of investigational product (IP);
- Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of IP;
- CYP3A4 strong inhibitor or strong inducer is used within 7 days prior to the first dose, or need to receive these drugs during the study period;
- Traditional Chinese medicine and traditional Chinese medicine preparations with anti-tumor as indications and with adjuvant treatment of tumor is used within 7 days prior to the first dose, or need to receive these drugs during the study period;
- Patients who are receiving drugs known to prolong QTc interval or may cause torsade de pointe and need to continue to receive these drugs during the study period;
- The time from the treatment with any other investigational product or its analogue to the first dose does not exceed 5 half-lives of the drug or 14 days, whichever is longer;
- Prior treatment with any systemic anti-cancer therapy for advanced Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiation including chemotherapy, biologic therapy, target therapy, immunotherapy, or any investigational drug, except neoadjuvant or adjuvant therapy before 6 months prior to the first dose;
- At the beginning of study treatment, any unresolved toxic reaction to prior treatment is present, which exceeds Grade 1 in accordance with Common Terminology Criteria for Adverse Events (CTCAE) (except for alopecia), and exceeds Grade 2 for prior platinum treatment-related neuropathy.
- Spinal cord compression; symptomatic and unstable brain metastases, except for those patients who have completed definitive therapy, are not on steroids, and have a stable neurological status for at least 2 weeks after completion of the definitive therapy and steroids.
- +10 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sun Yat-sen Universitylead
- Allist Pharmaceuticals, Inc.collaborator
- GeneCast Biotechnology Co., Ltd.collaborator
Study Sites (26)
The First Hospital of Jilin University
Changchun, China
Sichuan Provincial People's Hospital
Chengdu, China
Dongguan People's Hospital
Dongguan, China
Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang People's hospital
Dongyang, China
The First People's Hospital of Foshan
Foshan, China
Affiliated Cancer Hospital and Institute of Guangzhou Medical University
Guangzhou, China
Nanfang Hospital, Southern Medical University
Guangzhou, China
Sun Yat-sen University cancer center
Guangzhou, China
The First Affiliated Hospital, Sun Yat-sen University
Guangzhou, China
The First Affiliated Hospital, Zhejiang University School of Medicine
Hangzhou, China
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, China
Zhejiang Provincial Hospital of Chinese Medicine
Hangzhou, China
Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University
Jiangmen, China
Affiliated Jinhua Hospital, Zhejiang University School of Medicine
Jinhua, China
Mianyang Central Hospital
Mianyang, China
The First Affiliated Hospital of Nanchang University
Nanchang, China
Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute
Shenyang, China
Shijiazhuang People's hospital
Shijiazhuang, China
The Affiliated Cancer Hospital of Xinjiang Medical University
Ürümqi, China
The Third Affiliated Hospital of Wenzhou Medical University, Rui'an People's Hospital
Wenzhou, China
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, China
Yijishan Hospital, Wannan Medical College
Wuhu, China
Tangdu Hospital, Fourth Military Medical University
Xi'an, China
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, China
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, China
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
April 7, 2022
First Posted
April 19, 2022
Study Start
May 6, 2022
Primary Completion
February 28, 2025
Study Completion (Estimated)
February 29, 2028
Last Updated
August 31, 2022
Record last verified: 2022-08
Data Sharing
- IPD Sharing
- Will not share