Endocrine adverse reactions are one of the most common adverse reactions in the treatment of immune checkpoint inhibitors (ICIs), mainly involving the pituitary gland, pancreas, thyroid gland, adrenal gland and other glands, resulting in corresponding endocrine dysfunction. We report a 45-year-old man with non-small-cell lung cancer who developed hypophysitis 11 months after initiation of treatment with an anti-PD-L1/CTLA-4 bispecific antibody (KN046) that blocks both programmed death ligand-1 (PD-L1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), followed by regular oral replacement doses of prednisone and levothyroxine tablets. The patient was diagnosed with type 1 diabetes mellitus (T1DM) with diabetic ketoacidosis (DKA) 25 months after the start of immunotherapy, presenting with acute hyperglycemic symptoms, ketoacidosis, and negative diabetic autoantibodies. By describing a case of KN046 immunotherapy involving multiple endocrine glands and reviewing relevant literature, we were able to summarize the clinical characteristics of KN046 immunotherapy-induced endocrine system-related immune-related adverse events (irAEs) for use in early detection, diagnosis and treatment.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9041354 | PMC |
| http://dx.doi.org/10.2147/DMSO.S353403 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
First-line treatment with KN046, chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma: an open-label, dose escalation, and dose expansion phase Ib trial.
Cancer Immunol Immunother
August 2024
Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China.
Article Synopsis
- - The study explores the combination of KN046 (a bispecific antibody) with chemotherapy and palliative radiotherapy for treating advanced esophageal squamous cell carcinoma (ESCC) in an effort to enhance immunotherapy effectiveness.
- - In a phase Ib trial involving 25 patients, no dose-limiting toxicities were observed, with an objective response rate of 41.7% and a high disease control rate of 87.5%.
- - The treatment showed a median progression-free survival of 7.8 months and a median overall survival of 15.9 months, while serious adverse events occurred in 48% of patients, primarily related to immune-mediated effects.
A systematic review of antibody-drug conjugates and bispecific antibodies in head and neck squamous cell carcinoma and nasopharyngeal carcinoma: Charting the course of future therapies.
Cancer Treat Rev
July 2024
Head and Neck Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom; The Institute of Cancer Research, Division of Radiotherapy and Imaging, London, United Kingdom.
Introduction: There is a need to improve the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC), especially in recurrent unresectable and metastatic (R/M) setting. Antibody-drug conjugates (ADC) and bispecific antibodies (BsAb) may deliver promising results.
Methods: We conducted a systematic literature review to identify ADC and BsAb clinical trials, involving patients with HNSCC and NPC, from database creation to December 2023.
KN046, a bispecific antibody against PD-L1 and CTLA-4, plus chemotherapy as first-line treatment for metastatic NSCLC: A multicenter phase 2 trial.
Cell Rep Med
March 2024
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China. Electronic address:
KN046, a bispecific antibody targeting PD-L1 and CTLA-4, presents a promising therapeutic option for metastatic non-small cell lung cancer (NSCLC). In this multicenter phase 2 trial, patients with nonsquamous (non-sq) NSCLC receive pemetrexed, whereas those with sq-NSCLC receive paclitaxel, plus KN046 and carboplatin. Following four cycles, maintenance therapy includes KN046 with pemetrexed for non-sq-NSCLC and KN046 for sq-NSCLC.
View Article and Find Full Text PDFThe anti-PD-L1/CTLA-4 bispecific antibody KN046 in combination with nab-paclitaxel in first-line treatment of metastatic triple-negative breast cancer: a multicenter phase II trial.
Nat Commun
February 2024
State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Article Synopsis
- A phase II study evaluated the combination of the bispecific antibody KN046 and nab-paclitaxel for treating metastatic triple-negative breast cancer (TNBC), focusing on efficacy and safety.
- The study enrolled 27 female patients, finding an objective response rate (ORR) of 44% and a median progression-free survival (PFS) of 7.33 months, with positive outcomes particularly in PD-L1 positive patients.
- Overall, the combination therapy demonstrated favorable results in efficacy and survival benefits, indicating it could be a promising first-line treatment option for metastatic TNBC, warranting further investigation.
68Ga-FAPI PET imaging monitors response to combined TGF-βR inhibition and immunotherapy in metastatic colorectal cancer.
J Clin Invest
January 2024
Cancer Institute, Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.
BACKGROUNDImproving and predicting tumor response to immunotherapy remains challenging. Combination therapy with a transforming growth factor-β receptor (TGF-βR) inhibitor that targets cancer-associated fibroblasts (CAFs) is promising for the enhancement of efficacy of immunotherapies. However, the effect of this approach in clinical trials is limited, requiring in vivo methods to better assess tumor responses to combination therapy.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!