To Assess the Efficacy and Safety of Furmonertinib Versus Placebo, in Patients With Epidermal Growth Factor Receptor Mutation Positive Stage II-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy (FORWARD)
Primary Purpose
Non-small Cell Lung Carcinoma
Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Drug: Furmonertinib 80 mg
Furmonertinib 80 mg placebo
Sponsored by
About this trial
This is an interventional treatment trial for Non-small Cell Lung Carcinoma
Eligibility Criteria
Inclusion Criteria:
- Male or female, aged at least 18 years.
- Histologically confirmed diagnosis of primary non-small lung cancer (NSCLC) on predominantly non-squamous histology.
- MRI or CT scan of the brain must be done prior to surgery as it is considered standard of care.
- Patients must be classified post-operatively as Stage IB, II, or IIIA on the basis of pathologic criteria.
- Confirmation by the central laboratory that the tumor harbors one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations including T790M.
- Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for the tumor.
- Complete recovery from surgery and standard post-operative therapy (if applicable) at the time of randomization.
- World Health Organization Performance Status of 0 to 1.
- Female patients should be using adequate contraceptive measures, should not be breastfeeding, and must have a negative pregnancy test prior to the first dose of the study drug; or female patients must have evidence of non-child-bearing potential.
Exclusion Criteria:
- Pre-operative or post-operative or planned radiation therapy for the current lung cancer
- Pre-operative (neo-adjuvant) platinum-based or other chemotherapy
- Any prior anticancer therapy
- Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time
- Major surgery (including primary tumor surgery, excluding placement of vascular access) within 4 weeks of the first dose of study drug
- Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4
- Treatment with an investigational drug within five half-lives of the compound or any of its related material.
- Patients who have had only segmentectomies or wedge resections
- History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for > 5 years following the end of treatment.
- Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
- Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV).
- Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291.
- Any of the following cardiac criteria:
- Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG Machine-derived QTc value.
- Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
- Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
- Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
- Inadequate bone marrow reserve or organ function.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Furmonertinib
Placebo Furmonertinib
Arm Description
Furmonertinib (80 mg orally, once daily), in accordance with the randomization schedule.
Matching placebo for Furmonertinib (80 mg orally, once daily), in accordance with the randomization schedule.
Outcomes
Primary Outcome Measures
DFS
Disease free survival
Secondary Outcome Measures
Disease free survival (DFS) rate
Disease free survival (DFS) rate at 2, 3 and 5 years
Overall Survival (OS)
Defined as the time from the date of randomization until date of death due to any cause
Overall Survival rate at 5 years
Defined as the proportion of patients alive at 5 years, estimated from a Kaplan Meier plot of OS at the time of the primary analysis
Full Information
NCT ID
NCT04853342
First Posted
April 12, 2021
Last Updated
April 19, 2021
Sponsor
Allist Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04853342
Brief Title
To Assess the Efficacy and Safety of Furmonertinib Versus Placebo, in Patients With Epidermal Growth Factor Receptor Mutation Positive Stage II-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy
Acronym
FORWARD
Official Title
A Phase III, Double-blind, Randomized, Placebo-Controlled Multi-centre, Study to Assess the Efficacy and Safety of Furmonertinib (AST2818) Versus Placebo, in Patients With Epidermal Growth Factor Receptor Mutation Positive Stage II-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Not yet recruiting
Study Start Date
April 17, 2021 (Anticipated)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
January 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Allist Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This is a phase 3 double-blind, randomized, placebo-controlled, study to assess the efficacy and safety of Furmonertinib (AST2818) versus placebo in patients with stage II-IIIA non-small cell lung cancer (NSCLC) with centrally confirmed, most common sensitising EGFR mutations (Ex19Del and L858R) either alone or in combination with other EGFR mutations as confirmed by a central test, who have had complete tumour resection, with or without postoperative adjuvant chemotherapy.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-small Cell Lung Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
318 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Furmonertinib
Arm Type
Experimental
Arm Description
Furmonertinib (80 mg orally, once daily), in accordance with the randomization schedule.
Arm Title
Placebo Furmonertinib
Arm Type
Placebo Comparator
Arm Description
Matching placebo for Furmonertinib (80 mg orally, once daily), in accordance with the randomization schedule.
Intervention Type
Drug
Intervention Name(s)
Drug: Furmonertinib 80 mg
Intervention Description
The initial dose of Furmonertinib 80 mg once daily
Intervention Type
Drug
Intervention Name(s)
Furmonertinib 80 mg placebo
Intervention Description
The initial dose of Furmonertinib 80 mg once daily
Primary Outcome Measure Information:
Title
DFS
Description
Disease free survival
Time Frame
From date of randomization until date of disease recurrence or death (by any cause in the absence of recurrence). Estimated median time to event of 60 months for those treatment) [ Time Frame: Up to 5 years]
Secondary Outcome Measure Information:
Title
Disease free survival (DFS) rate
Description
Disease free survival (DFS) rate at 2, 3 and 5 years
Time Frame
Time Frame: From date of randomization until date of disease recurrence or death (by any cause in the absence of recurrence)Estimated median time to event of 60 months for those treatment[ Time Frame: Up to 5 years]
Title
Overall Survival (OS)
Description
Defined as the time from the date of randomization until date of death due to any cause
Time Frame
Time Frame: From date of randomization until date of death due to any cause Estimated median time to event of 60 months for those treatment[ Time Frame: Up to 5 years]
Title
Overall Survival rate at 5 years
Description
Defined as the proportion of patients alive at 5 years, estimated from a Kaplan Meier plot of OS at the time of the primary analysis
Time Frame
Time Frame: From date of randomization until date of death due to any cause about 5years[ Time Frame: Up to 5 years]
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female, aged at least 18 years.
Histologically confirmed diagnosis of primary non-small lung cancer (NSCLC) on predominantly non-squamous histology.
MRI or CT scan of the brain must be done prior to surgery as it is considered standard of care.
Patients must be classified post-operatively as Stage IB, II, or IIIA on the basis of pathologic criteria.
Confirmation by the central laboratory that the tumor harbors one of the 2 common EGFR mutations known to be associated with EGFR-TKI sensitivity (Ex19del, L858R), either alone or in combination with other EGFR mutations including T790M.
Complete surgical resection of the primary NSCLC is mandatory. All gross disease must have been removed at the end of surgery. All surgical margins of resection must be negative for the tumor.
Complete recovery from surgery and standard post-operative therapy (if applicable) at the time of randomization.
World Health Organization Performance Status of 0 to 1.
Female patients should be using adequate contraceptive measures, should not be breastfeeding, and must have a negative pregnancy test prior to the first dose of the study drug; or female patients must have evidence of non-child-bearing potential.
Exclusion Criteria:
Pre-operative or post-operative or planned radiation therapy for the current lung cancer
Pre-operative (neo-adjuvant) platinum-based or other chemotherapy
Any prior anticancer therapy
Prior treatment with neoadjuvant or adjuvant EGFR-TKI at any time
Major surgery (including primary tumor surgery, excluding placement of vascular access) within 4 weeks of the first dose of study drug
Patients currently receiving medications or herbal supplements known to be potent inducers of cytochrome P450 (CYP) 3A4
Treatment with an investigational drug within five half-lives of the compound or any of its related material.
Patients who have had only segmentectomies or wedge resections
History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other solid tumors curatively treated with no evidence of disease for > 5 years following the end of treatment.
Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy.
Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses; or active infection including hepatitis B, hepatitis C, and human immunodeficiency virus (HIV).
Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of AZD9291.
Any of the following cardiac criteria:
Mean resting corrected QT interval (QTc) >470 msec, obtained from 3 ECGs, using the screening clinic ECG Machine-derived QTc value.
Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG.
Any factors that increase the risk of QTc prolongation or risk of arrhythmic events, or unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval.
Past medical history of ILD, drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
Inadequate bone marrow reserve or organ function.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianxing He, PHD
Phone
020-83062114
Email
drjianxing.he@gmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Wenhua Liang, PHD
Phone
020-83062114
Email
liangwh1987@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jianxing He, PHD
Organizational Affiliation
The First Affiliated Hospital of Guangzhou Medical University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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To Assess the Efficacy and Safety of Furmonertinib Versus Placebo, in Patients With Epidermal Growth Factor Receptor Mutation Positive Stage II-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy
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