Locally advanced or metastatic ALK-positive non-small cell lung cancer
Conditions
Interventions
CROWN Criteria (CC) Cohort:Study treatment cycles were divided into 28-day cycles (including baseline visits within 2 weeks prior to enrollment). From the first dose (according to the current regimen)
Compassionate use (CU) Cohort:Study treatment cycles were divided into 28-day cycles (including baseline visits within 2 weeks prior to enrollment). From the first dose (according to the current regim
Sponsors
Guangdong Provincial People's Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria of CROWN Criteria (CC) Cohort Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Diagnosis: a. Study Population: Patients with histologically or cytologically confirmed diagnosis of locally advanced [(Stage IIIB/C, not suitable for surgery/chemoradiotherapy) or metastatic (Stage IV) by American Joint Committee on Cancer (AJCC) v 8.0] ALK-positive NSCLC where ALK status is determined by the Ventana ALK (D5F3) Companion Diagnostic (CDx) IHC test performed on the Ventana ULTRA or XT Platforms, FISH, PCR, or next generation sequencing (NGS), or circulating tumor DNA (ctDNA). b. Tumor Requirements: According to RECIST v. 1.1, there is at least one extracranial measurable lesion that has not undergone radiation therapy before, allowing for asymptomatic central nervous system (CNS) metastasis, while meeting the following conditions: 1) Either untreated and not currently requiring corticosteroid treatment, or on a stable or decreasing dose of =10 mg QD prednisone or equivalent; 2) Local treatment has been completed before enrollment and has fully recovered from the acute effects of radiation therapy or surgery, and the acute effects of radiation therapy or surgery have fully recovered before the first medication. Corticosteroid therapy for these metastases has been stopped for at least 4 weeks and the nervous system is stable; 3) For leptomeningeal lesions (LMD) or carcinomatous meningitis (CM), magnetic resonance imaging (MRI) can display or baseline cerebrospinal fluid cytology examination is positive. c. Tissue Requirements: All patients must have an archival formalin fixed, paraffin embedded (FFPE) tissue specimen available and collected before enrollment. If archived tissue is unavailable, then a mandatory de novo biopsy must be performed. 2. There has been no systematic treatment for locally advanced (IIIB/C stage, not suitable for surgery/chemotherapy) or metastatic (IV stage) non-small cell lung cancer in the past, including molecular targeted drugs (such as ALK TKIs), angiogenesis inhibitors, immunotherapy, or chemotherapy. Early NSCLC can be enrolled after treatment, but the time to enrollment must be greater than 12 months. 3. Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, or 2. 4. Age =18 years. 5. Adequate Bone Marrow Function, including: a. Absolute Neutrophil Count (ANC) = 1,500/mm3 or =1.5 x 10^9/L; b. Platelets =100,000/mm3 or =100 x 10^9/L; c. Hemoglobin =9 g/dL. 6. Adequate Pancreatic Function, including: a. Serum total amylase =1.5 x upper limit of normal (ULN)*; b. Serum lipase =1.5 x ULN. *if total amylase >1.5 x ULN, but pancreatic amylase is within the ULN, then patient may be enrolled. 7. Adequate Renal Function, including: a. Serum creatinine =1.5 x ULN or estimated creatinine clearance =60 mL/min as calculated using the method standard for the institution. 8. Adequate Liver Function, including: a. Total serum bilirubin =1.5 x ULN; b. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) =2.5 x ULN (=5.0 x ULN in case of liver metastases). 9. Acute effects of prior radiotherapy resolved to baseline severity or to CTCAE Grade =1 except for AEs that in the investigator’s judgment do not constitute a safety risk for the patient. 10. Serum pregnancy test (for females of childbearing potential) negative at screening. Female patients of non-childbearing potential must meet at least 1 of the following criteria: a.
Exclusion criteria
Exclusion criteria: 1. Spinal cord compression unless the patient has good pain control attained through therapy, and there is stabilization or recovery of neurological function for the 4 weeks before enrollment. 2. Major surgery within 4 weeks before enrollment. Minor surgical procedures (e.g., port insertion) are not excluded, but sufficient time should have passed for adequate wound healing. 3. Radiation therapy within 2 weeks before enrollment, including stereotactic or partial brain irradiation. Patients who complete whole brain irradiation within 4 weeks before enrollment or palliative radiation therapy outside of the CNS within 48 hours before enrollment will also not be included in the study. 4. Gastrointestinal abnormalities, including inability to take oral medication; requirement for intravenous alimentation; prior surgical procedures affecting absorption including total gastric resection or lap band; active inflammatory gastrointestinal disease, chronic diarrhea, symptomatic diverticular disease; treatment for active peptic ulcer disease in the past 6 months; malabsorption syndromes. 5. Known prior or suspected severe hypersensitivity to study drugs or any component in their formulations. 6. Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV) or hepatitis C virus (HCV) (e.g., in case of known HBsAg or HCV antibody positivity), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness. 7. Clinically significant vascular (both arterial and venous) and non-vascular cardiac conditions, (active or within 3 months prior to enrollment), which may include, but are not limited to: a. Arterial disease such as cerebral vascular accident/stroke (including Transient Ischemic Attack -TIA), myocardial infarction, unstable angina; b. Venous diseases such as cerebral venous thrombosis, symptomatic pulmonary embolism; c. Non-vascular cardiac disease such as congestive heart failure (New York Heart Association Classification Class = II), second-degree or third-degree AV block (unless paced) or any AV block with PR >220 msec; or ongoing cardiac dysrhythmias of NCI CTCAE Grade =2, uncontrolled atrial fibrillation of any grade, bradycardia defined as 470 msec, or congenital long QT syndrome. 8. According to the researchers' judgment, there were susceptibility features of acute pancreatitis in the last month before enrollment (such as uncontrolled hyperglycemia, gallstones, and other diseases). 9. History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis. 10. Evidence of active malignancy (other than NSCLC, non-melanoma skin cancer, or localized prostate cancer or any in situ cancer which does not currently require treatment) within the last 3 years before enrollment. 11. Concurrent use of any of the following food or drugs (consult the sponsor if in doubt whether a food or a drug falls into any of the above categories) within 12 days prior to the first dose of lorlatinib. a. Known strong CYP3A inhibitors (e.g., strong CYP3A inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits [eg, Seville
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PFS;Drug resistance mechanism; | — |
Secondary
| Measure | Time frame |
|---|---|
| Antitumor activity;OS;Safety and tolerability;Quality of life ;ORR; | — |
Countries
China
Contacts
Public ContactYilong Wu; Jiaxin Lin
Guangdong Provincial People's Hospital (Huifu Branch)
Outcome results
None listed