Metastatic Non-Small Cell Lung Cancer, Advanced Non-Small Cell Lung Cancer, EGFR Exon 20 Mutations
Conditions
Keywords
Non-Small Cell Lung Cancer (NSCLC), Exon 20, Furmonertinib, Firmonertinib, AST2818, FURMO-004, Drug-Therapy
Brief summary
Global, Phase 3, randomized, multicenter, open-label study evaluating the efficacy and safety of furmonertinib (firmonertinib) 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.
Interventions
DRUGfurmonertinib 240 mg oral, daily
furmonertinib tablet
DRUGfurmonertinib 160 mg oral, daily
furmonertinib tablet
(carboplatin or cisplatin based on investigator's choice) + pemetrexed intravenously (IV)
Sponsors
Allist Pharmaceuticals, Inc.
ArriVent BioPharma, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression Free Survival (PFS) determined by blinded independent central review (BICR) | Up to 32 months after first dose |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Overall Survival (OS) | Up to 62 months after first 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) | Randomization up to ≤30 days after last dose | 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). |
| Change in EORTC QLQ Lung Cancer Module Core 13 (QLQ LC13) | Randomization up to ≤30 days after last dose | 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. |
| Change in Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC SAQ) | Randomization up to ≤30 days after last dose | NSCLC-SAQ consists of 7 items assessing 5 NSCLC symptom concepts: cough, pain, dyspnea, fatigue, and poor appetite. |
| 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 | — |
| CNS DOR evaluated by BICR | Randomization up to ≤30 days after last dose | — |
Countries
Australia, Brazil, Canada, China, France, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, Philippines, Singapore, South Korea, Spain, Taiwan, Thailand, United Kingdom, United States
Outcome results
None listed