ALK, Iruplinalkib, Lorlatinib, Non-Small Cell Lung Cancer, Observational Study, Real-world Study
Conditions
Keywords
Iruplinalkib, ALK-postive, Post-Lorlatinib, Advanced Lung Adenocarcinoma
Brief summary
This observational study aims to evaluate the real-world effectiveness and safety of iruplinalkib in patients with advanced ALK-positive lung adenocarcinoma who have progressed on or are intolerant to prior lorlatinib therapy. The results are expected to provide real-world evidence to inform clinical decision-making for this heavily pretreated patient population.
Detailed description
Background & Unmet Need: Lorlatinib, a third-generation ALK tyrosine kinase inhibitor (TKI), is a standard treatment option for patients with advanced ALK-positive lung adenocarcinoma, particularly following the failure of earlier-generation ALK inhibitors. Despite its potent central nervous system penetration and broad coverage of ALK resistance mutations, acquired resistance and disease progression remain inevitable for most patients. Currently, there is no established standard of care for patients who progress on lorlatinib, representing a significant unmet clinical need. Rationale for Iruplinalkib: Iruplinalkib is a novel ALK inhibitor exhibiting high selectivity and activity against a broad spectrum of ALK resistance mutations, including those associated with resistance to prior ALK TKIs. While preliminary clinical studies have demonstrated promising antitumor activity and a manageable safety profile in patients with ALK-positive non-small cell lung cancer (NSCLC), data specifically evaluating iruplinalkib in the post-lorlatinib setting are limited, particularly within real-world clinical practice. Study Objectives: This study is designed as an observational investigation to assess the real-world effectiveness and safety of iruplinalkib in patients with advanced ALK-positive lung adenocarcinoma who have received prior lorlatinib treatment. The study will include eligible patients who are prescribed iruplinalkib as part of routine clinical practice. This study aims to characterize the clinical benefit of iruplinalkib and explore its potential role as a subsequent-line treatment option in this specific population.
Interventions
180mg, QD
Sponsors
Peking University Shenzhen Hospital
Shenzhen People's Hospital
Longgang District People's Hospital of Shenzhen
Sun Yat-sen University Cancer Hosptial
Eighth Affiliated Hospital, Sun Yat-sen University
The First Affiliated Hospital of Guangzhou Medical University
People Hospital of New District Longhua Shenzhen
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Population: Male or female patients aged ≥18 years. 2. Diagnosis: Histologically or cytologically confirmed advanced lung adenocarcinoma. 3. Molecular Status: Documentation of ALK rearrangement confirmed by a validated test (e.g., NGS, IHC, FISH). 4. Prior Therapy: Prior treatment with lorlatinib (in any line of therapy), with documented disease progression or intolerance. 5. Current Therapy: Initiated treatment with iruplinalkib in the real-world setting. 6. Measurability: Presence of at least one evaluable lesion (measurable or non-measurable) for response assessment. 7. Data Availability: availability of key clinical data (baseline characteristics, treatment history, and follow-up outcomes).
Exclusion criteria
1. Lack of Exposure: Patients who never actually received iruplinalkib or took only a trivial amount (e.g., \< 1 week/cycle) before withdrawal for non-medical reasons. 2. Wrong Diagnosis: Active malignancy of other histological types (excluding treated basal cell carcinoma, etc.). 3. Confounding: Participation in another interventional clinical trial involving an investigational anti-tumor drug concurrently. 4. Pregnancy: Pregnant or breastfeeding women. 5. Data Quality: Missing critical medical records that preclude assessment of primary endpoints (e.g., unknown start date, unknown prior therapy).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Real-World Progression-Free Survival (rwPFS) | From index date through study completion, an average of 36 months | Time from treatment initiation to the earliest of death or clinical disease progression. Progression is defined by the treating provider's assessment recorded in the medical record, based on radiology, laboratory, or physical exam findings, distinct from RECIST-based radiographic progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Next Treatment (TTNT) | From index date to the start of next line of therapy, assessed up to 36 months | TTNT is defined as the time interval from the index date (date of first dose of the study treatment) to the date of the first administration of a new (subsequent) systemic anti-cancer therapy. This outcome distinguishes the duration of the current line of therapy before a switch is made. Patients who die without receiving a subsequent therapy are censored at the date of death. Patients who remain on the study treatment or discontinue treatment without starting a new line are censored at their last known activity date or the data cutoff date. |
| Overall survival (OS) | From index date through study completion, an average of 36 months | To assess overall survival, define as first dose to the death of the subject due to any cause |
| Treatment-related adverse reactions ( TRAE ) | From the index date through the date of Iruplinalkib discontinuation or the start of a new anti-cancer therapy (whichever occurs first), assessed up to 36 months. | All AEs will be evaluated by the investigators to determine their potential relationship to iruplinalkib treatment based on clinical judgment, temporal association, and alternative etiologies. Events assessed as possibly, probably, or definitely related to iruplinalkib will be classified as treatment-related adverse reactions (TRAEs). The TRAEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, 5.0). Serious adverse events (SAEs) will be identified and recorded in accordance with standard definitions or are considered medically significant by the investigator. |
Countries
China
Contacts
CONTACTFEN WANG
Outcome results
None listed