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 with Epidermal Growth Factor Receptor Exon 20 Insertion Mutations

Phase 3

• Conditions: on-squamous nonsmall cell lung cancer; Lung cancer; patients with advanced or metastatic non-small cell lung cancer (NSCLC); 10038666; 10029107

• Registration Number: NL-OMON53471
• Lead Sponsor: ArriVent BioPharma, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Last Update Posted: 9 April 2024

Recruitment & Eligibility

• Status: Pending
• Sex: Not specified
• Target Recruitment: 2

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 <= 1.5 × upper limit of normal (ULN) or <= 3 × ULN in the
presence of documented Gilbert*s Syndrome (unconjugated hyperbilirubinemia)
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and
alkaline phosphatase (AP) <= 2.5 × ULN, with the following exceptions:
* Patients with documented liver metastases may have AST, ALT, and/or AP <= 5.0
× ULN.
* Patients with documented bone metastases may have AP <= 5.0 × ULN.
• Creatinine clearance >= 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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>PFS, where PFS is defined as the time from randomization to the first<br /><br>occurrence of disease progression, as determined by blinded independent central<br /><br>review (BICR) using Response Evaluation Criteria in Solid Tumors, version 1.1<br /><br>(RECIST v1.1), or death from any cause, whichever occurs first</p><br>