Inclusion Criteria:
1. Male or female, age in 18-75 years.
2. The Eastern Cooperative Oncology Group (ECOG) physical status score is 0-2 and has
not deteriorated in the previous 2 weeks, with a minimum expected survival of 12
weeks.
3. Histologically confirmed patients with NSCLC leptomeningeal metastasis by positive
cerebrospinal fluid cytological examination.
4. Tumor tissue samples or blood are confirmed to be EGFR sensitive mutations
(including exon 19 deletion or L858R).
5. There must be at least one measurable extracranial lesion that has not been locally
treated at the time of enrollment.
6. Females should be using adequate contraceptive measures throughout the study; should
not be breastfeeding at the time of screening, during the study and until 3 months
after completion of the study; and must have a negative pregnancy test prior to
start of dosing if of childbearing potential or must have evidence of
non-childbearing potential by fulfilling 1 of the following criteria at Screening:
a) Postmenopausal defined as age more than 50 years and amenorrheic for at least 12
months following cessation of all exogenous hormonal treatments. b) Women under 50
years old would be considered postmenopausal if they have been amenorrheic for 12
months or more, following cessation of exogenous hormonal treatments, and with
luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the
postmenopausal range for the laboratory. c) Documentation of irreversible surgical
sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy,
but not by tubal ligation.
7. Male patients should be willing to use barrier contraception (i.e., condoms).
8. For inclusion in study, patient must provide a written informed consent.
Exclusion Criteria:
1. Treatment with any of the following: a) Prior treatment with systemic anti-cancer
therapy for locally advancer or metastatic NSCLC including chemotherapy, biologic
therapy, immunotherapy, or any investigational drug. b) Prior treatment with an EGFR
TKI. c) Major surgery (excluding placement of vascular access) within 4 weeks of the
first dose of study drug. d) Radiotherapy with a limited field of radiation for
palliation within 4 week of the first dose of study drug, with the exception of
patients receiving radiation to > 30% of the bone marrow or with a wide field of
radiation within 4 weeks of the first dose of study drug. e) Medications that are
predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4
with a narrow therapeutic range within 7 days of the first dose of study drug.
2. Patients with other malignancies, except basal cell carcinoma and carcinoma in situ.
3. Any unresolved toxicities from prior therapy greater than Common Terminology
Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment,
with the exception of alopecia and Grade 2, prior platinum-therapy related
neuropathy.
4. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled
hypertension or active bleeding diatheses, which, in the Investigator's opinion,
makes it undesirable for the patient to participate in the trial OR which would
jeopardize compliance with the protocol such as active infection. Screening for
chronic conditions is not required..
5. Refractory nausea, vomiting, or chronic gastrointestinal diseases, inability to
swallow the study drug, or previous significant bowel resection that would preclude
adequate absorption of Almonertinib.
6. Any of the following cardiac criteria: a) Mean resting corrected QT interval (QTc) >
470 ms obtained from 3 electrocardiograms (ECGs), using the screening clinic's ECG
machine and Fridericia's formula for QT interval correction (QTcF). b) Any
clinically important abnormalities in rhythm, conduction, or morphology of the
resting ECG (e.g., complete left bundle branch block, third-degree heart block,
second-degree heart block, PR interval > 250 ms). c) Any factors that increase the
risk of QTc prolongation or risk of arrhythmic events, such as heart failure,
hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or
unexplained sudden death under 40 years of age in first degree relatives or any
concomitant medication known to prolong the QT interval. d) Left ventricular
ejection fraction (LVEF)< 50%.
7. Inadequate bone marrow reserve or organ function, as demonstrated by any of the
following laboratory values: a) Absolute neutrophil count (ANC) <1.5×10^9 / L. b)
Platelet count <100×10^9 / L. c) Hemoglobin <90 g/L (<9 g/dL). d) Alanine
aminotransferase > 2.5 × upper limit of normal (ULN) if no demonstrable liver
metastases or > 5 × ULN in the presence of liver metastases. e) Aspartate
aminotransferase (AST) > 2.5 × ULN if no demonstrable liver metastases or > 5 × ULN
in the presence of liver metastases. f) Total bilirubin (TBL) > 1.5 × ULN if no
liver metastases or > 3 × ULN in the presence of documented Gilbert's Syndrome
(unconjugated hyperbilirubinemia) or liver metastases. g) Creatinine > 1.5 × ULN
concurrent with creatinine clearance < 50 mL/min (measured or calculated by the
Cockcroft-Gault equation); confirmation of creatinine clearance is only required
when creatinine is > 1.5 × ULN. h) ALB <28 g/L.
8. Past medical history of interstitial lung disease, drug-induced interstitial lung
disease, radiation pneumonitis that required steroid treatment, or any evidence of
clinically active interstitial lung disease.
9. Women who are breastfeeding or have a positive urine or serum pregnancy test at the
Screening Visit.
10. History of hypersensitivity to any active or inactive ingredient of Almonertinib, or
to drugs with a similar chemical structure or class to Almonertinib.
11. Judgment by the Investigator that the patient should not participate in the study if
the patient is unlikely to comply with study procedures, restrictions, and
requirements.
12. Any severe and uncontrolled ocular disease that may, in the ophthalmologist's
opinion, present a specific risk to the patient's safety.
13. Any disease or condition that, in the opinion of the Investigator, would compromise
the safety of the patient or interfere with study assessments.
