Iruplinalkib in ALK-Positive Advanced Lung Adenocarcinoma After Lorlatinib

Официальное название

An Observational Study of the Efficacy and Safety of Iruplinalkib(WX-0593) in ALK-positive Advanced Lung Adenocarcinoma Following Lorlatinib Treatment

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Iruplinalkib tablets
  180mg, QD

Первичные конечные точки

• Real-World Progression-Free Survival (rwPFS) [Срок оценки: From index date through study completion, an average of 36 months]

Вторичные конечные точки (3)

• Time to Next Treatment (TTNT) [Срок оценки: From index date to the start of next line of therapy, assessed up to 36 months]
• Overall survival (OS) [Срок оценки: From index date through study completion, an average of 36 months]
• Treatment-related adverse reactions ( TRAE ) [Срок оценки: 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.]

Критерии участия

Критерии включения

• Population: Male or female patients aged ≥18 years.
• Diagnosis: Histologically or cytologically confirmed advanced lung adenocarcinoma.
• Molecular Status: Documentation of ALK rearrangement confirmed by a validated test (e.g., NGS, IHC, FISH).
• Prior Therapy: Prior treatment with lorlatinib (in any line of therapy), with documented disease progression or intolerance.
• Current Therapy: Initiated treatment with iruplinalkib in the real-world setting.
• Measurability: Presence of at least one evaluable lesion (measurable or non-measurable) for response assessment.
• Data Availability: availability of key clinical data (baseline characteristics, treatment history, and follow-up outcomes).

Критерии исключения

• 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.
• Wrong Diagnosis: Active malignancy of other histological types (excluding treated basal cell carcinoma, etc.).
• Confounding: Participation in another interventional clinical trial involving an investigational anti-tumor drug concurrently.
• Pregnancy: Pregnant or breastfeeding women.
• Data Quality: Missing critical medical records that preclude assessment of primary endpoints (e.g., unknown start date, unknown prior therapy).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• Peking University Shenzhen Hospital — Шэньчжэнь

Публикации

• Shi Y, Fang J, Hao X, Zhang S, Liu Y, Wang L, Chen J, Hu Y, Hang X, Li J, Liu C, Zhang Y, Wang Z, Hu Y, Gu K, Huang J, Zhang L, Shan J, Ouyang W, Zhao Y, Zhuang W, Yu Y, Zhao J, Zhang H, Lu P, Li W, Si M, Ge M, Geng H. Safety and activity of WX-0593 (Iruplinalkib) in patients with ALK- or ROS1-rearranged advanced non-small cell lung cancer: a phase 1 dose-escalation and dose-expansion trial. Signa PMID 35087031
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• Raskova Kafkova L, Mierzwicka JM, Chakraborty P, Jakubec P, Fischer O, Skarda J, Maly P, Raska M. NSCLC: from tumorigenesis, immune checkpoint misuse to current and future targeted therapy. Front Immunol. 2024 Feb 7;15:1342086. doi: 10.3389/fimmu.2024.1342086. eCollection 2024. PMID 38384472
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Идентификаторы

NCT: NCT07374614 · 2025-324

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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