Idris Omer A, Westgate Diana, Saadaie Jahromi Bahar, Shebrain Abdulaziz, Zhang Tiantian, Ashour Hossam M
Department of Biological Sciences, Western Michigan University, Kalamazoo, MI 49008, USA.
Malate Institute for Medical Research, Malate Inc., Grandville, MI 49468, USA.
Biomedicines. 2025 Apr 7;13(4):889. doi: 10.3390/biomedicines13040889.
Cutaneous squamous cell carcinoma (CSCC) is one of the most common non-melanoma skin cancers, and particularly challenging to treat in advanced or metastatic stages. Traditional therapies, including chemotherapy and radiation, often result in limited efficacy and severe side effects. Cosibelimab, a fully human monoclonal antibody targeting PD-L1, has emerged as a promising immunotherapy for advanced CSCC. In this review, we evaluate the therapeutic potential of cosibelimab by analyzing its mechanism of action, clinical trial data, and its role compared to other PD-1/PD-L1 inhibitors, such as pembrolizumab and cemiplimab. We synthesized the available preclinical and clinical data on cosibelimab, focusing on published Phase I and II trial results involving 76 patients. Objective response rates (ORRs), progression-free survival (PFS), overall survival (OS), and safety profiles were compared between cosibelimab, pembrolizumab, and cemiplimab. Mechanistic insights into cosibelimab's dual action, including PD-L1 blockade and antibody-dependent cellular cytotoxicity (ADCC), were also explored. Phase II trials demonstrated an ORR of 47.5%, with a median PFS of 12.9 months in advanced CSCC patients. Cosibelimab demonstrated a favorable safety profile, with predominantly mild to moderate adverse events. Comparative analysis with pembrolizumab and cemiplimab showed similar efficacy, although long-term survival data for cosibelimab is still emerging. Given its efficacy and safety, cosibelimab holds promise not only as a monotherapy but also for future exploration in combination regimens and broader oncologic indications. Future trials are required to validate its long-term outcomes, including overall survival, and to explore its use in combination therapies and neoadjuvant/adjuvant settings.
皮肤鳞状细胞癌（CSCC）是最常见的非黑色素瘤皮肤癌之一，在晚期或转移阶段的治疗尤其具有挑战性。包括化疗和放疗在内的传统疗法往往疗效有限且副作用严重。Cosibelimab是一种靶向PD-L1的全人源单克隆抗体，已成为晚期CSCC有前景的免疫疗法。在本综述中，我们通过分析其作用机制、临床试验数据以及与其他PD-1/PD-L1抑制剂（如帕博利珠单抗和西米普利单抗）相比的作用，评估Cosibelimab的治疗潜力。我们综合了关于Cosibelimab的现有临床前和临床数据，重点关注涉及76例患者的已发表的I期和II期试验结果。比较了Cosibelimab、帕博利珠单抗和西米普利单抗的客观缓解率（ORR）、无进展生存期（PFS）、总生存期（OS）和安全性。还探讨了对Cosibelimab双重作用的机制见解，包括PD-L1阻断和抗体依赖性细胞毒性（ADCC）。II期试验显示晚期CSCC患者的ORR为47.5%，中位PFS为12.9个月。Cosibelimab显示出良好的安全性，主要是轻度至中度不良事件。与帕博利珠单抗和西米普利单抗的比较分析显示疗效相似，尽管Cosibelimab的长期生存数据仍在不断涌现。鉴于其疗效和安全性，Cosibelimab不仅有望作为单一疗法，而且在联合方案和更广泛的肿瘤适应症方面的未来探索中也有前景。需要未来的试验来验证其长期结果，包括总生存期，并探索其在联合治疗和新辅助/辅助治疗中的应用。
