Idafang (ivonescimab)

P1, N=30, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P2, N=40, Not yet recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

As multi-target combination therapy is an essential strategy for overcoming resistance, we analyze key combination targets - such as vascular endothelial growth factor (VEGF), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and lymphocyte activation gene 3 (LAG-3) - and highlight the clinical success of novel dual-target regimens such as ivonescimab (PD-1/VEGF). Furthermore, we discuss potential approaches to overcoming resistance from both microenvironmental (e.g., targeting cancer-associated fibroblasts or utilizing antibody-drug conjugates) and macroenvironmental (e.g., modulating the microbiota or sex hormones) perspectives. This review provides a forward-looking framework for designing precision- and mechanism-driven combination therapies aimed at converting non-responders into responders.

We report a 72-year-old man with stage IV squamous NSCLC harboring an EGFR mutation and PD-L1 tumor proportion score of 90% who developed persistent fever shortly after first exposure to ivonescimab combined with nab-paclitaxel and carboplatin. His prior treatments included concurrent chemoradiotherapy, osimertinib, the investigational EGFR inhibitor BH-30643, afatinib, and recent gamma knife for cerebellar metastases plus palliative radiotherapy for bone metastases...Symptoms improved with corticosteroids, tocilizumab, and desmopressin, consistent with probable arginine vasopressin deficiency (AVP-D), possibly secondary to hypophysitis-though pituitary metastasis cannot be ruled out without biopsy...Advanced age, EGFR-mutant/PD-L1-high tumor biology, recent radiotherapy, and Parkinsonism may have contributed to the inflammatory environment, though none can be proven causal in a single case and each deserves prospective study. Early recognition of persistent steroid-responsive fever, serial IL-6 monitoring, thorough endocrine workup, and timely IL-6 blockade are critical.

P2/3, N=220, Recruiting, Summit Therapeutics Inc. | Not yet recruiting --> Recruiting

P2, N=31, Recruiting, City of Hope Medical Center | Not yet recruiting --> Recruiting

P2, N=132, Not yet recruiting, Akeso

P2, N=30, Not yet recruiting, Sun Yat-sen University

P2, N=158, Not yet recruiting, European Organisation for Research and Treatment of Cancer - EORTC | Trial completion date: Oct 2031 --> Apr 2032 | Initiation date: Apr 2026 --> Nov 2026 | Trial primary completion date: Jan 2031 --> Jan 2032

P=N/A, N=80, Recruiting, Peking University People's Hospital | Active, not recruiting --> Recruiting

P1/2, N=265, Not yet recruiting, Akeso

P1, N=16, Recruiting, Memorial Sloan Kettering Cancer Center