Non-squamous nonsmall cell lung cancer Lung cancer patients with advanced or metastatic non-small cell lung cancer (NSCLC)
Conditions
Interventions
For this study, furmonertinib, pemetrexed, carboplatin, and cisplatin are
considered investigational medicinal products (IMPs).
Furmonertinib is manufactured by WuXi SynTheAll Pharmaceutical Co., Ltd
Sponsors
ArriVent BioPharma, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: atients must meet the following criteria for study entry: 1. Signed Informed Consent Form 2. Age >= 18 years at time of signing Informed Consent Form 3. Ability to comply with the study protocol, in the investigator*s judgment 4. Measurable disease per RECIST v1.1 Note: Measurable lesion can neither be subject to local therapy such as radiotherapy nor used for biopsy in the Screening Period; if there is only 1 measurable lesion, this lesion will be permitted to be biopsied. However, the baseline radiologic examination should be performed for this lesion at least 14 days after biopsy. 5. Histologically or cytologically documented, locally advanced or metastatic non-squamous NSCLC not amenable to curative surgery or radiotherapy 6. Documented validated results confirming the presence of an EGFR exon 20 insertion mutation (i.e., addition of 1 or more amino acids) in tumor tissue or blood from local or central testing via: • A validated next-generation sequencing (NGS) assay or a validated polymerase chain reaction (PCR) test with confirmation by Sanger sequencing performed at a Clinical Laboratory Improvement Amendments (CLIA) or equivalently certified laboratory. * If local testing does not meet the above criteria, then a central test designated by the Sponsor or a commercially available NGS assay should be performed as specified in the laboratory manual. 7. Consent to provide archival tumor tissue specimen (formalin-fixed, paraffin-embedded [FFPE] tissue block [preferred] or at least 15 unstained, serially cut sections on slides from FFPE tumor specimen). The specimens should be provided during screening or no later than within 30 days of Cycle 1, Day 1 and must be accompanied by a pathology report. • It is preferred that the specimen is prepared from the most recently collected and available tumor tissue. See the laboratory manual for instructions. 8. No prior systemic anticancer therapy regimens received for locally advanced or metastatic NSCLC including prior treatment with any EGFR-targeting agents (e.g., previous EGFR tyrosine kinase inhibitors (EGFR-TKIs), monoclonal antibodies, or bispecific antibodies) 9. Patients who have received prior neo-adjuvant and/or adjuvant chemotherapy, immunotherapy, or chemoradiotherapy for non-metastatic disease must have experienced a treatment-free interval of at least 12 months. 10. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 11. Life expectancy of >= 12 weeks 12. Adequate hematologic and organ function within 14 days prior to initiation of study treatment, defined by the following: • Absolute neutrophil count >= 1500/µL • Hemoglobin >= 9 g/dL • Platelet count >= 100,000/µL • Total bilirubin = 45 mL/min on the basis of the Cockcroft-Gault estimation: (140 - age) × (weight in kg) × (0.85 if female) 72 × (serum creatinine in mg/dL)
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from study entry: 1. Inability or unwillingness to swallow pills 2. Inability to comply with study and follow-up procedures 3. Malabsorption syndrome or other conditions that would interfere with enteral absorption 4. Pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures biweekly or more frequently • Indwelling pleural or abdominal catheters may be allowed, provided the patient has adequately recovered from the procedure, is hemodynamically stable, and has symptomatically improved. 5. Severe acute or chronic infections, including: • Uncontrolled acute infection, active infection that necessitates systemic treatment, or systemic antibiotic treatment within 2 weeks prior to the first dose of investigational product. • Patients with uncontrolled human immunodeficiency virus (HIV) infection (defined as CD4+ T cell count < 350 cells/µL). Note: Patients must have been on established antiretroviral therapy (ART) for at least four weeks and have an HIV viral load < 400 copies/mL prior to enrollment). If the lower limit of detection of HIV viral load assay at the site is higher than 400 copies/mL or with units other than copies/mL, patients with an HIV viral load result lower than the lower limit of detection in the site are considered eligible. Patients with unknown HIV infection status who do not agree to take HIV test are not eligible. • Patients with active chronic hepatitis B or with active hepatitis C infection, which includes patients who are hepatitis B surface antigen (HBsAg)-positive or hepatitis C virus (HCV) antibody-positive at screening, are not eligible until further definite quantitative testing of hepatitis B virus (HBV) DNA (e.g., <= 2500 copies/mL or 500 IU/mL) and HCV ribonucleic acid (RNA) tests (e.g., <= lower limit of detection) can conclusively rule out presence of active hepatitis B or C infection that requires treatment. Note: If a patient has a negative HBsAg test and a positive total HbcAb test at screening, an HBV DNA test must also be performed to determine if the patient has an HBV infection. Patients who are carriers of HBV, with stable HBV infection (e.g., HBV DNA quantitative test showed DNA <= 2500 copies/mL or 500 IU/mL) after medical treatment or with cured hepatitis C are permitted to enroll. If the lower limit of detection of HBV DNA assay in the site is higher than 2500 cps/mL or 500 IU/mL, patients with HBV DNA quantitative test result lower than the lower limit of detection in the site are considered eligible. 6. In the setting of a pandemic or epidemic, screening for active infections should be considered according to local or institutional guidelines or those of applicable professional societies (e.g., American Society of Clinical Oncology or European Society for Medical Oncology). 7. Previous interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis, or active ILD 8. History of or active clinically significant cardiovascular dysfunction, including the following: • History of stroke or transient ischemic attack within 6 months prior to first dose of study drug • History of myocardial infarction within 6 months prior to first dose of study drug • New York Heart Association (NYHA) Class III or IV cardiac dis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS, where PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by blinded independent central review (BICR) using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first | — |
Secondary
| Measure | Time frame |
|---|---|
| OS, defined as the time from randomization to death from any cause • PFS as determined by investigator assessment using RECIST v1.1 • Objective response rate (ORR), defined as the percentage of patients with a complete response (CR) or partial response (PR) relative to the total number of patients by BICR and investigator assessment using RECIST v1.1 • Duration of response (DOR), defined as the time from first documented evidence of CR or PR until the first documented evidence of disease progression or death, whichever occurs earlier, as determined by BICR and investigator assessment using RECIST v1.1 Furmonertinib*ArriVent BioPharma, Inc. 16/Protocol FURMO-004 Version 2.0 • Time to second progression (PFS2), defined as the time from randomization to second progression, (i.e., earliest of the subsequent progression events after initiation of new anticancer treatment), or death from any cause, whichever occurs first. PFS2 is evaluated per local standard practice by investigator. • PFS by BICR and investigator assessment using RECIST v1.1 in patients with a history or presence of brain metastases at baseline • Time to central nervous system (CNS) metastases by BICR and investigator assessment using RECIST v1.1 * Time to CNS metastases is defined as the time from the date of randomization until the date of newly diagnosed CNS lesions by RECIST v1.1. • CNS ORR, evaluated by BICR per modified RECIST criteria in patients with CNS lesion(s) on baseline brain scan • CNS DOR, evaluated by BICR per modified RECIST criteria in patients with CNS lesion(s) on baseline brain scan • CNS PFS, evaluated by BICR per modified RECIST criteria in patients with CNS lesion(s) on baseline brain scan * CNS PFS is defined as the time from randomization to the first occurrence of CNS progression according to modified RECIST by BICR, or death from any cause, whichever comes first. Change from baseline in European Organisation for Research and Treatment of Cancer | — |
Countries
Netherlands
Outcome results
None listed