A Phase 1b Dose Escalation and Dose Expansion Study Evaluating the Safety, Pharmacokinetics, and Antitumor Activity of Furmonertinib in Patients with Advanced or Metastatic Non-Small Cell Lung Cancer with Activating EGFR or HER2 Mutations
- Conditions
- Patients with Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) with mutations in a gene called epidermal growth factor receptor (EGFR)/Lung Cancer10038666
- Registration Number
- NL-OMON53437
- Lead Sponsor
- ArriVent BioPharma, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 5
Patients must meet the following criteria for study entry:
General Inclusion Criteria
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 target lesions (TLs) can neither be subject to local therapy
such as radiotherapy nor used for biopsy in the screening period; if there is
only one measurable TL, this TL will be permitted to be biopsied. However, the
baseline radiologic examination should be performed for this lesion at least 14
days after biopsy.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Life expectancy of >= 12 weeks
7. 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
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 ×
ULN with the following exception:
- Patients with documented liver metastases may have AST and/or ALT <= 5.0 × ULN
• Creatinine clearance >= 30 mL/min based on the Cockcroft-Gault estimation:
(140 * age) × (weight in kg) × (0.85 if female)
72 × (serum creatinine in mg/dL)
• International normalized ratio (INR) <= 1.5 × ULN and activated partial
thromboplastin time (aPTT) <= 1.5 × ULN
Note: This applies only to patients who are not receiving therapeutic
anticoagulation. Patients receiving therapeutic anticoagulation should be on a
stable dose for at least 1 week prior to Cycle 1, Day 1.
8. For women of childbearing potential (WOCBPs): Agreement to remain abstinent
(refrain from heterosexual intercourse) or use contraception, and agreement to
refrain from donating eggs, as defined below:
• A woman is considered to be of childbearing potential if she is
postmenarchal, has not reached a postmenopausal state >= 12 continuous months of
amenorrhea with no identified cause other than menopause), and is not
permanently infertile due to surgery (i.e., removal of ovaries, fallopian
tubes, and/or uterus) or another cause as determined by the investigator (e.g.,
Müllerian agenesis). The definition of childbearing potential may be adapted
for alignment with local guidelines or regulations.
• WOCBPs must remain abstinent or use a barrier method such as a condom plus an
additional contraceptive method that together result in a failure rate of < 1%
per year during the treatment period and at least 60 days after the final dose
of furmonertinib. WOCBPs must refrain from donating eggs during the treatment
period and 6 months after the final dose of furmonertinib.
• Examples of contraceptive methods with a failure rate of < 1% per year
include bilateral tubal ligation, male sterilization, hormonal oral
contraceptives that inhibit ovulation, hormone-releasing intrauterine devices,
and copper intrauterine devices.
Note: The reliability of sexual abstinence should be evaluated in relation to
the duration of the clinical trial and the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or
pos
General Exclusion Criteria
Patients who meet any of the following criteria will be excluded from study
entry:
1. Inability or unwillingness to swallow pills
1. Inability to comply with study and follow-up procedures
2. Malabsorption syndrome or other condition that would interfere with enteral
absorption
3. 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 symptomatically improved, and after discussion with the Sponsor.
4. 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 furmonertinib.
• Known history of human immunodeficiency virus (HIV) infection and/or acquired
immune deficiency syndrome. Patients with unknown HIV infection status who
don*t 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 RNA tests (e.g., <= lower
limit of detection) can conclusively rule out presence of active hepatitis B or
C infection that requires treatment.
Note: 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.
5. 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
[ASCO] or European Society for Medical Oncology [ESMO]).
6. Previous interstitial lung disease (ILD), drug induced ILD, radiation
pneumonitis; or active ILD.
7. 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 furmonertinib
• History of myocardial infarction within 6 months prior to first dose of
furmonertinib
• New York Heart Association Class III or IV cardiac disease or congestive
heart failure requiring medication
• Uncontrolled arrhythmias, history of or active ventricular arrhythmia
requiring medication
• Coronary heart disease that is symptomatic or unstable angina
8. Mean resting QT interval corrected through use of Fridericia*s formula
(QTcF) > 470 ms, obtained from triplicate electrocardiograms (ECGs), using the
screening clinic ECG machine-derived QTcF value.
9. Clinically significant prolonged QT interval or other arrhythmia or clinical
status considered by investigators that may increase t
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Stage 1 Primary Endpoint<br /><br>• Incidence and severity of adverse events (AEs), including DLTs, with severity<br /><br>determined according to National Cancer Institute Common Terminology Criteria<br /><br>for Adverse Events, Version 5.0 (NCI CTCAE v5.0)<br /><br>Stage 2 Primary Endpoints<br /><br>• Stage 2, Cohorts 1, 2, and 3 only: Confirmed ORR, defined as the percentage<br /><br>of patients with a confirmed CR or PR relative to the total number of patients.<br /><br>Confirmation of the response is based on a subsequent assessment, at least 28<br /><br>days later, as determined by investigator assessment using RECIST v1.1<br /><br>• Stage 2, Cohort 4 only: Confirmed ORR as determined by BICR assessment using<br /><br>RECIST v1.1</p><br>
- Secondary Outcome Measures
Name Time Method