Cadonilimab is a programmed death-1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) bispecific antibody independently developed in China, and is also the world's first approved PD-1/CTLA-4 bispecific antibody. By simultaneously blocking two immunosuppressive pathways, PD-1/CTLA-4, as well as its own structural advantages, it not only improves the therapeutic effect of malignant tumours, but also reduces the risk of toxicity and improves the quality of life of patients. Cadonilimab is currently approved for two indications, including for the first-line treatment of patients with locally advanced unresectable or metastatic adenocarcinoma of the stomach or gastro-oesophageal junction and for the treatment of recurrent or metastatic cervical cancer, and has been the subject of many clinical studies in a variety of advanced solid tumours, including liver cancer, lung cancer, pancreatic cancer and esophageal squamous carcinoma. This article reviewed the latest clinical progress of cadonilimab in terms of its mechanism of action, clinical research, safety and other aspects to provide reference for its subsequent research and clinical application.
HomeArticlesVol 35,2025 No.6Detail
Clinical progress of cadonilimab in the treatment of malignant tumor
Published on Jun. 25, 2025Total Views: 17774 timesTotal Downloads: 2979 timesDownloadMobile
- Abstract
- Full-text
- References
Abstract
Full-text
References
1.Hang Y, Huang J, Ding M, et al. Extracellular vesicles reshape the tumor microenvironment to improve cancer immunotherapy: current knowledge and future prospects[J]. Int Immunopharmacol, 2024, 140: 112820. DOI: 10.1016/j.intimp.2024.112820.
2.Lefler DS, Manobianco SA, Bashir B. Immunotherapy resistance in solid tumors: mechanisms and potential solutions[J]. Cancer Biol Ther, 2024, 25(1): 2315655. DOI: 10.1080/15384047.2024.2315655.
3.张天奇, 曹钰哲, 左孟轩, 等, 肝癌靶向联合免疫治疗耐药后的二线治疗方案研究进展[J]. 临床肝胆病杂志, 2024, 40(2): 386-390. [Zhang TQ, Cao YZ, Zuo MX, et al. Research advances in second-line therapies for hepatocellular carcinoma after resistance to targeted therapy combined with immunotherapy[J]. Journal of Clinical Hepatology, 2024, 40(2): 386-390.] DOI: 10.12449/JCH240227.
4.André T, Lonardi S, Wong KYM, et al. Nivolumab plus low-dose ipilimumab in previously treated patients with microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: 4-year follow-up from CheckMate 142[J]. Ann Oncol, 2022, 33(10): 1052-1060. DOI: 10.1016/j.annonc.2022.06.008.
5.Zhang T, Lin Y, Gao Q. Bispecific antibodies targeting immunomodulatory checkpoints for cancer therapy[J]. Cancer Biol Med, 2023, 20(3): 181-195. DOI: 10.20892/j.issn.2095-3941. 2023.0002.
6.Pang X, Huang Z, Zhong T, et al. Cadonilimab, a tetravalent PD-1/CTLA-4 bispecific antibody with trans-binding and enhanced target binding avidity[J]. MAbs, 2023, 15(1): 2180794 DOI: 10.1080/19420862.2023.2180794.
7.Liang W, Guo Z, Zhang Y, et al. Infusion-related reactions induced by cadonilimab (PD-1/CTLA-4 bispecific antibody): seven case reports[J]. Case Rep Oncol, 2024, 17(1): 361-369. DOI: 10.1159/000535504.
8.Huang Z, Pang X, Zhong T, et al. Penpulimab, an FC-engineered IgG1 Anti-PD-1 antibody, with improved efficacy and low incidence of immune-related adverse events[J]. Front Immunol, 2022, 13: 924542. DOI: 10.3389/fimmu.2022.924542.
9.Tsukamoto H, Fujieda K, Miyashita A, et al. Combined blockade of IL6 and PD-1/PD-L1 signaling abrogates mutual regulation of their immunosuppressive effects in the tumor microenvironment[J]. Cancer Res, 2018, 78(17): 5011-5022. DOI: 10.1158/0008-5472.Can-18-0118.
10.Gao X, Xu N, Li Z, et al. Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial[J]. Lancet Oncol, 2023, 24(10): 1134-1146. DOI: 10.1016/s1470-2045(23)00411-4.
11.Lou H, Cai H, Huang X, et al. Cadonilimab combined with chemotherapy with or without bevacizumab as first-line treatment in recurrent or metastatic cervical cancer (COMPASSION-13): a phase 2 study[J]. Clin Cancer Res, 2024, 30(8): 1501-1508. DOI: 10.1158/1078-0432.Ccr-23-3162.
12.Wu X, Sun Y, Yang H, et al. Cadonilimab plus platinum-based chemotherapy with or without bevacizumab as first-line treatment for persistent, recurrent, or metastatic cervical cancer (COMPASSION-16): a randomised, double-blind, placebo-controlled phase 3 trial in China[J]. Lancet, 2024, 404(10463): 1668-1676. DOI: 10.1016/s0140-6736(24)02135-4.
13.Tang J, Tian W, Huang S, et al. An open, prospective, single arm, phase II study of cadonilimab (PD-1/CTLA-4 bispecific antibody) with neoadjuvant chemotherapy in patients with advanced ovarian cancer: interim analysis from the AK104-IIT-003 study[J]. J Clin Oncol, 2024, 42(16_suppl): e17552. DOI: 10.1200/JCO.2024.42.16_suppl.e17552.
14.Lan C, Yang X, Zhao J, et al. Cadonilimab plus lenvatinib in patients with advanced endometrial cancer: a multicenter, single-arm, phase II trial[J]. J Clin Oncol, 2024, 42(16_suppl): 5600. DOI: 10.1200/JCO.2024.42.16_suppl.5600.
15.Zhang Q, Liu Z, Zhang J, et al. Efficacy and safety of cadonilimab plus anti-EGFR monoclonal antibody as de-chemotherapy regimen in persistent, recurrent, or metastatic gynecologic cancer[J]. J Clin Oncol, 2024, 42(16_suppl): 5538. DOI: 10.1200/JCO.2024.42.16_suppl.5538.
16.Gao X, Ji K, Jia Y, et al. Cadonilimab with chemotherapy in HER2-negative gastric or gastroesophageal junction adenocarcinoma: the phase 1b/2 COMPASSION-04 trial[J]. Nat Med, 2024, 30(7): 1943-1951. DOI: 10.1038/s41591-024-03007-5.
17.Shen L, Zhang Y, Li Z, et al. First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial[J]. Nat Med, 2025, 31(4): 1163-1170. DOI: 10.1038/s41591-024-03450-4.
18.Keam SJ. Cadonilimab: first approval[J]. Drugs, 2022, 82(12): 1333-1339. DOI: 10.1007/s40265-022-01761-9.
19.Cheng W, Kang K, Zhao A, et al. Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in lung cancer[J]. J Hematol Oncol, 2024, 17(1): 54. DOI: 10.1186/s13045-024-01581-2.
20.Zhao Y, Ma Y, Fan Y, et al. A multicenter, open-label phase Ib/II study of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) monotherapy in previously treated advanced non-small-cell lung cancer (AK104-202 study)[J]. Lung Cancer, 2023, 184, 107355. DOI: 10.1016/j.lungcan.2023.107355.
21.Cheng Y, Fan Y, Zhao Y, et al. Tislelizumab plus platinum and etoposide versus placebo plus platinum and etoposide as first-line treatment for extensive-stage SCLC (RATIONALE-312): a multicenter, double-blind, placebo-controlled, randomized, phase 3 clinical trial[J]. J Thorac Oncol, 2024, 19(7): 1073-1085. DOI: 10.1016/j.jtho.2024.03.008.
22.Mathew D, Marmarelis ME, Foley C, et al. Combined JAK inhibition and PD-1 immunotherapy for non-small cell lung cancer patients[J]. Science, 2024, 384(6702): eadf1329. DOI: 10.1126/science.adf1329.
23.Zhong H, Sun S, Chen J, et al. First-line penpulimab combined with paclitaxel and carboplatin for metastatic squamous non-small-cell lung cancer in China (AK105-302): a multicentre, randomised, double-blind, placebo-controlled phase 3 clinical trial[J]. Lancet Respir Med, 2024, 12(5): 355-365. DOI: 10.1016/s2213-2600(23)00431-9.
24.Zhou C, Hu Y, Arkania E, et al. A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004) [J]. Cancer Cell, 2024, 42(2): 198-208. e3. DOI: 10.1016/j.ccell.2023.12.004.
25.Li H, Zhao W, Li C, et al. The efficacy and safety of a novel PD-1/CTLA-4 bispecific antibody cadonilimab (AK104) in advanced non-small cell lung cancer: a multicenter retrospective observational study[J]. Thorac Cancer, 2024, 15(32): 2327-2338. DOI: 10.1111/1759-7714.15455.
26.Qiao Q, Han C, Ye S, et al. The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma (COMPASSION-08): a phase Ib/II single-arm clinical trial[J]. Front Immunol, 2023, 14, 1238667. DOI: 10.3389/fimmu.2023.1238667.
27.Yuan G, Chen Y, Zhu P, et al. Cadonilimab (PD-1/CTLA-4) in combination with lenvatinib in unresectable hepatocellular carcinoma (uHCC): a retrospective real-world study[J]. Heliyon, 2024, 10(19): e37616. DOI: 10.1016/j.heliyon.2024.e37616.
28.Qu W, Gao J, Zhang B, et al. Efficacy, safety and DNA methylation analysis of cadonilimab combined with taxane and cisplatin as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): updated results from an open-label, multicenter phase II trial (AK104-IIT-014)[J]. J Clin Oncol, 2025, 43(4_suppl): 463. DOI: 10.1200/JCO.2025.43.4_suppl.463.
29.Miao H, Fu S, Ruan L, et al. 1446P Efficacy and safety of cadonilimab combined albumin-paclitaxel, cisplatin and fluorouracil (APF) in neoadjuvant therapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC): results from the CAPITAL trial[J]. Ann Oncol, 2024, 35: S898-S899. DOI: 10.1016/j.annonc.2024.08.1512.
30.Wahafu W, Wei S, Qiao X, et al. Disitamab vedotin (DV, RC48-ADC) combined with cadonilimab (anti-PD-1/CTLA-4 bispecific antibody) in patients with locally advanced or metastatic urothelial carcinoma (la/mUC): an open-label, single-arm, phase II study[J]. J Clin Oncol, 2024, 42(16_suppl): e16572. DOI: 10.1200/JCO.2024.42.16_suppl.e16572.
31.Chen QY, Guo SS, Luo Y, et al. Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma (COMPASSION-06): a phase II multicenter study[J]. Oral Oncol, 2024, 151: 106723. DOI: 10.1016/j.oraloncology.2024.106723.
32.Frentzas S, Gan HK, Cosman R, et al. A phase 1a/1bfirst-in-humanstudy (COMPASSION-01) evaluating cadonilimabinpatients withadvancedsolidtumors[J]. Cell Rep Med, 2023, 4(11): 101242. DOI: 10.1016/j.xcrm.2023.101242.
33.Mai H, Lin S, Chen D, et al. A phase II study of AK104, a bispecific antibody targeting PD-1 and CTLA-4, in patients with metastatic nasopharyngeal carcinoma (NPC) who had progressed after two or more lines of chemotherapy[J]. J Immunother Cancer, 2021, 9(Suppl 2): A1-A1054. https://doi.org/10.1136/jitc-2021-SITC2021.436.
Popular Papers
-
Analysis of burden of type 2 diabetes mellitus and its attributable risk factors in global and China from 1990 to 2021
Feb. 02, 20268457
-
Meta-integration of qualitative studies on the inner experience and nursing needs of breast cancer patients during radiotherapy and chemotherapy
Feb. 02, 20267600
-
Detection value of umbilical artery pulsatility index in growth-restricted fetuses
Feb. 02, 20266342
-
Meta-analysis of the incidence and influencing factors of sleep disorders in patients with coronary heart disease
Feb. 02, 20266245
-
Constructing a depression risk prediction model for elderly people with activities of daily living impairment based on machine learning algorithms
Feb. 02, 20266172
-
The relationship between exercise duration, sleep duration, and depressive symptoms in adults in China: an empirical study based on the CFPS database 2022
Feb. 02, 20265748
-
Research on living clinical practice guidelines in diabetes mellitus II: summary of key evidence in the development of drug treatment strategies for type 2 diabetes mellitus
Mar. 05, 20265272
-
Application of digital teaching mode in outpatient general practice professional master training
Feb. 02, 20265239
-
Construction of a predictive model of deep vein thrombosis in elderly patients with hip fractures
Feb. 02, 20265203
-
The research progress of fibroblast growth factor 21 in retinal neovascularization diseases
Feb. 02, 20265053
-
Efficacy and safety of SOX chemotherapy combined with Sintilimab immunotherapy in treatment of patients with advanced gastric cancer
Feb. 02, 20264980
-
SOX9 promotes ovarian cancer progression through activating ferroptosis via SLC7A11/GPX4 pathway
Feb. 02, 20264929
-
AURKA promotes Temozolomide resistance in glioma cells by inhibiting ferroptosis through activation of the JAK2/STAT3 pathway
Feb. 02, 20264889
-
Research on living clinical practice guidelines in diabetes mellitus Ⅰ: a qualitative study of public-oriented web-based knowledge platform and guideline dissemination
Feb. 02, 20264884
-
Correlation between epidemiological characteristics and meteorological factors in critically ill patients with respiratory failure
Feb. 02, 20264853
Welcome to visit Zhongnan Medical Journal Press Series journal website!