An ambispective, observational, multi-center study of first-line Lorlatinib in patients with ALK-positive non-small cell lung cancer in Korea (Lorlatinib NIS)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  LORVIQUA
• Study drug International non-proprietary name (INN) or common name:
  LORLATINIB
• Anatomical Therapeutic Chemical (ATC) code:
  (L01ED05) lorlatinib

  lorlatinib
• Medical condition to be studied:
  Non-small cell lung cancer

Population studied

• Short description of the study population:
  The study population consists of adult patients (≥19 years) with ALK-positive NSCLC who initiated first‑line lorlatinib treatment on or after December 01, 2021, the market launch date in Korea. These patients represent the real-world population receiving routine lorlatinib treatment consistent with its locally approved indication.
• Estimated number of subjects:
  103

Study design details

• Study design:
  This study is an ambispective, non-interventional, observational, multi-center cohort study of patients who have received lorlatinib as a part of routine clinical practice prescribed by accredited physicians at Korean healthcare centers.
• Main study objective:
  Primary objective; • To evaluate the real-world effectiveness of first-line lorlatinib in patients with ALK-positive NSCLC in Korea, as measured by real-world objective response rate (ORR), real-world progression-free survival (PFS), and overall survival (OS).; Secondary objectives ; • To further characterize the real-world effectiveness of first-line lorlatinib in patients with ALK-positive NSCLC in Korea, including intracranial effectiveness, duration of response, and disease control.; • To describe the frequency and incidence of adverse events (AEs), adverse drug reactions (ADRs), unexpected AEs/ADRs, serious adverse events (SAEs), serious adverse drug reactions (SADRs), and unexpected SAEs/SADRs among patients receiving first-line lorlatinib in routine clinical practice in Korea.; • To further describe adverse events of special interest, severity of adverse events, and actions taken in response to adverse events among patients receiving first-line lorlatinib in routine clinical practice in Korea.; • To describe real-world treatment patterns associated with first-line lorlatinib use, including time to treatment discontinuation, time to next treatment, prior and subsequent systemic anti-cancer therapies, concomitant medications, treatment re-initiation following temporary interruption, and continuation of lorlatinib beyond disease progression.; Exploratory Objectives; • To explore clinical and treatment-related factors associated with early progression on lorlatinib, including genetic profiles when available.; • To explore intracranial disease management patterns among patients with baseline brain metastases, including the use and timing of brain-directed radiotherapy.; • To explore treatment re-initiation characteristics following temporary interruption of lorlatinib due to adverse events, including time to treatment re-initiation and dose at re-initiation.;
• Setting:
  This study will be conducted at multiple healthcare centers in Korea where lorlatinib is prescribed as part of routine clinical practice. Eligible patients with ALK-positive NSCLC who initiate first-line lorlatinib treatment will be enrolled and followed according to routine clinical care. Patient enrollment is planned from January 2027 through July 2028. The study is expected to continue until approximately January 2029, including follow-up and data collection activities.
• Comparators:
  None
• Outcomes:
  Primary Endpoint; • Real-world Objective Response Rate (ORR); • Overall survival (OS); • Real-world Progression free survival (PFS); Secondary Endpoint; • Real-world Intracranial Objective Response Rate (IC-ORR); • Real-world Intracranial Progression free survival (IC-PFS); • Duration of Response (DoR); • Disease control rate (DCR) ; • Time-to-treatment discontinuation (TTD); • Time to next treatment (TTNT) ; • Frequency and incidence rates of AEs/ADRs, unexpected AEs/ADRs, SAEs/SADRs, and unexpected SAEs/SADRs; • Frequency and incidence rates of AESIs; • Severity of AEs (graded per NCI CTCAE v5.0).; • Actions taken for AEs (treatment interruption, dose reduction, withdrawal); Exploratory Endpoints; • Time to brain-directed radiotherapy; • Time to lorlatinib treatment re-initiation following temporary interruption due to adverse events; • Dose at re initiation of lorlatinib treatment following temporary interruption due to adverse events; • Treatment continuation pattern of lorlatinib beyond disease progression; • Patterns of Prior and Subsequent Systemic Anti‑Cancer Therapy (SACT); • Use of Concomitant Medications; • Exploration of Early Progression on lorlatinib;