Study to Compare Furmonertinib to Platinum-Based Chemotherapy for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations (FURVENT)

Study Overview
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Brief Summary
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Global, Phase 3, randomized, multicenter, open-label study evaluating the efficacy and safety of furmonertinib at 2 dose levels (160 mg once daily [QD] and 240 mg QD) compared to platinum-based chemotherapy in previously untreated patients with locally advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) exon 20 insertion mutations. A target of approximately 375 patients will be randomized in a 1:1:1 ratio to treatment with furmonertinib 240 mg QD, furmonertinib 160 mg QD, or platinum-based chemotherapy.

Official Title
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A Global, Phase 3, Randomized, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Furmonertinib Compared to Platinum-Based Chemotherapy as First-Line Treatment for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertion Mutations (FURVENT)

Conditions
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EGFR Exon 20 Mutations, Metastatic Non-Small Cell Lung Cancer, Advanced Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: furmonertinib 240 mg oral, daily
* Drug: furmonertinib 160 mg oral, daily
* Drug: platinum-based chemotherapy


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Histologically or cytologically documented, locally advanced or metastatic non-squamous Non-Small Cell Lung Cancer (NSCLC) not amenable to curative surgery or radiotherapy. Documented results of the presence of an Epidermal Growth Factor Receptor (EGFR) exon 20 insertion mutation in tumor tissue or blood from local or central testing. No prior systemic anticancer therapy regimens received for locally advanced or metastatic Non-Small Cell Lung Cancer (NSCLC) including prior treatment with any Epidermal Growth Factor Receptor (EGFR)-targeting agents (e.g., previous (EGFR) TKIs, monoclonal antibodies, or bispecific antibodies). Patients who have received prior neo-adjuvant and/or adjuvant chemotherapy, immunotherapy, or chemo radiotherapy for non-metastatic disease (excluding EGFR-TKIs) must have experienced a treatment free interval of at least 12 months. Patients with a history of treated CNS metastases or new asymptomatic CNS metastases are eligible.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: furmonertinib 240 mg<br> | Drug: furmonertinib 240 mg oral, daily<br>* furmonertinib tablet<br>* Other names: AST2818;|
| Experimental: furmonertinib 160 mg<br> | Drug: furmonertinib 160 mg oral, daily<br>* furmonertinib tablet<br>* Other names: AST2818;|
| Active Comparator: platinum-based chemotherapy<br>carboplatin or cisplatin based on investigator's choice + pemetrexed intravenously | Drug: platinum-based chemotherapy<br>* (carboplatin or cisplatin based on investigator's choice) + pemetrexed intravenously (IV)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) determined by blinded independent central review (BICR) |  | Up to 32 months after first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) |  | Up to 62 months after first dose | 
| PFS determined by investigator assessment |  | Up to 36 months after first dose | 
| Overall response rate (ORR) |  | Up to 36 months after first dose | 
| Duration of response (DOR) |  | Up to 36 months after first dose | 
| Time to second Progression Free Survival (PFS2) |  | Up to 36 months after first dose | 
| PFS by blinded independent central review (BICR) in patients with a history or presence of brain metastases at baseline |  | Up to 36 months after first dose | 
| Time to central nervous system (CNS) metastases by BICR |  | Randomization up to ≤30 days after last dose | 
| CNS ORR evaluated by BICR |  | Randomization up to ≤30 days after last dose | 
| CNS DOR evaluated by BICR |  | Randomization up to ≤30 days after last dose | 
| CNS PFS evaluated by BICR |  | Randomization up to ≤30 days after last dose | 
| Change in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30) | QLQ-C30 is a cancer-specific questionnaire comprised of 5 functional scales (physical, role, cognitive, emotional, and social functioning); 3 symptom scales (fatigue, pain, and nausea/vomiting); and a global health status/quality-of-life (QoL) scale. Six single-item scales are also included (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). | Randomization up to ≤30 days after last dose | 
| Change in EORTC QLQ Lung Cancer Module Core 13 (QLQ LC13) | QLQ-LC13 is a cancer-specific questionnaire which comprises of 13 questions assessing lung cancer-associated symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and use of pain medication. | Randomization up to ≤30 days after last dose | 
| Change in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC SAQ) | NSCLC-SAQ consists of 7 items assessing 5 NSCLC symptom concepts: cough, pain, dyspnea, fatigue, and poor appetite. | Randomization up to ≤30 days after last dose | 
| Number of incidence and severity of adverse events (AEs) as a measure of safety and tolerability of Furmonertinib |  | Up to 36 months after first dose | 
| Plasma concentrations of furmonertinib and its major metabolite (AST5902) |  | Up to 36 months after first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer (NSCLC), Exon 20, Furmonertinib, FURMO-004, Drug-Therapy