Ivonescimab combined with chemotherapy shows promising efﬁcacy in an ALK fusion-positive lung adenocarcinoma patient with ALK-TKI resistance - a case report

Sep 28, 2026

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A rare case report describes a lung adenocarcinoma with EML4–ALK fusion, high PD-L1 expression (TPS 75%), and a BIM deletion polymorphism, initially treated with alectinib but followed by rapid progression. After repeat genetic testing, therapy was changed to lorlatinib, again leading to early progression. Subsequent treatment with ivonescimab combined with chemotherapy produced a favorable clinical response, representing the first reported ivonescimab use in this specific ALK-TKI–resistant setting and offering reference value for personalized management.

LanguageEnglish

CategoryHealthcare

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Introduction

Case presentation

TYPE Case Report PUBLISHED 18 December 2025 DOI 10.3389/fonc.2025.1723763 OPEN ACCESS EDITED BY James C. M. Ho, The University of Hong Kong, Hong Kong SAR, China REVIEWED BY Rita Leporati, University of Modena and Reggio Emilia, Italy Roland Leung, Queen Mary Hospital, Hong Kong SAR, China *CORRESPONDENCE Jun Deng [dj2882@sina.com](dj2882@sina.com) †These authors have contributed equally to this work and share ﬁrst authorship RECEIVED 13 October 2025 REVISED 27 November 2025 ACCEPTED 04 December 2025 PUBLISHED 18 December 2025 CITATION Lin M, Gao Y and Deng J (2025) Ivonescimab combined with chemotherapy shows promising efﬁcacy in an ALK fusion-positive lung adenocarcinoma patient with ALK-TKI resistance: a case report. Front. Oncol. 15:1723763 . doi: 10.3389/fonc.2025.1723763 COPYRIGHT © 2025 Lin, Gao and Deng. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Ivonescimab combined with chemotherapy shows promising efﬁcacy in an ALK fusion-positive lung adenocarcinoma patient with ALK-TKI resistance: a case report Meiyuan Lin †, Yuan Gao † and Jun Deng* Department of Respiratory and Critical Care Medicine, The Afﬁliated Hospital of Southwest Medical University, Luzhou, Sichuan, China This report describes a case of lung adenocarcinoma harboring an echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase (EML4–ALK) fusion, high programmed death-ligand 1 (PD-L1) expression, and a Bcl-2-like protein 11 (BIM) deletion polymorphism. The patient was initially treated with alectinib, but experienced rapid disease progression. After repeat genetic testing, therapy was switched to lorlatinib, which again resulted in early progression. Subsequently, treatment with ivonescimab combined with chemotherapy achieved a favorable clinical response. To our knowledge, this is the ﬁrst reported case of ivonescimab use in such a patient. This case offers a potential reference for the management of ALK fusion–positive lung adenocarcinoma resistant to ALK tyrosine kinase inhibitors (ALK-TKIs) . KEYWORDS ivonescimab, non–small cell lung cancer, ALK fusion, drug resistance, BIM deletion polymorphism, case report Introduction Lung cancer poses a serious threat to human health and remains the leading cause of cancer-related deaths worldwide. Approximately 60% of patients with lung adenocarcinoma harbor driver gene alterations, and about 2%–7% of these cases exhibit anaplastic lymphoma kinase (ALK) fusions (1) . For patients with advanced non–small cell lung cancer (NSCLC) harboring ALK fusions, targeted therapy has become the standard ﬁrst-line treatment, including ﬁrst-generation (e.g., crizotinib), second-generation (e.g., alectinib), and third-generation (e.g., lorlatinib) ALK tyrosine kinase inhibitors (ALKTKIs) (2–5). Although the use ofALK-TKIs has signiﬁcantly improved clinical outcomes in this population, the inevitable emergence of drug resistance remains a major clinical challenge (6) . Therefore, identifying effective subsequent treatment strategies for ALK Frontiers in Oncology 01 [frontiersin.org](frontiersin.org) fusion–positive NSCLC patients who experience disease progression after ALK-TKI therapy has become a key focus of current research. We report a rare case of ALK fusion–positive lung adenocarcinoma with concurrent high programmed death-ligand 1 (PD-L1) expression and a Bcl-2-like protein 11 (BIM) deletion polymorphism. The patient exhibited resistance to both secondand third-generation ALK-TKIs but achieved a sustained clinical response to ivonescimab co

FAQs

What molecular features were identified in the patient’s lung adenocarcinoma?

The case described an EML4–ALK fusion, high PD-L1 expression (TPS 75%), and a BIM deletion polymorphism.

How did the patient respond to alectinib and lorlatinib?

The patient experienced rapid progression after initial alectinib treatment and again showed early progression after switching to lorlatinib.

What treatment led to a favorable clinical response in this case?

Ivonescimab combined with chemotherapy achieved a favorable clinical response after ALK-TKI resistance.

Sep 28, 2026

Uploaded by Asher