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Globally first dual immune checkpoint inhibitor bi-specific antibody approved for marketing
开坦尼® (PD-1/CTLA-4 Bi-specific Antibody, Cadonilimab Injection)
开坦尼® (Cadonilimab injection) is a novel, first-in-class PD-1/CTLA-4 bi-specific immunotherapy drug in-house developed by the Company, which is mainly used in the treatment of gastric cancer, liver cancer, lung cancer, cervical cancer, pancreatic carcinoma, esophageal squamous carcinoma and other malignant tumors. The research data show that, as compared with the combination therapy of PD-1 and CTLA-4, Cadonilimab demonstrates promising safety profile and efficacy.
On June 29th, 2022, 开坦尼® has been granted marketing approval by the NMPA of China for the treatment of relapsed or metastatic cervical cancer (R/M CC) patients who progressed on or after platinum-based chemotherapy. In September 2024，a new indication for cadonilimab has been approved for first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma，in combination with fluoropyrimidine and platinum-based chemotherapy. Currently, the new drug applications for Cadonilimab combined with platinum-based chemotherapy, with or without bevacizumab, for the first-line treatment of persistent, recurrent, or metastatic cervical cancer has been accepted by the CDE. Additionally, a series of clinical studies, including a phase III trial for adjuvant therapy in patients with a high risk of recurrence following curative resection of hepatocellular carcinoma, are being efficiently conducted.
Three major mechanisms of action
①Dual functions: It blocks both CTLA-4 and PD-1 immune checkpoint pathways
·Block both CTLA-4 and PD-1 immune checkpoint pathways
·Bind to both PD-1 and CTLA-4
·PD-1 and CTLA-4 binding activity is comparable to that of the corresponding single-target antibodies
②Efficacy: It restores the “immune normalization” of the tumor microenvironment in multiple ways
·Effectively mediate the endocytosis of PD-1 and CTLA-4 receptors on the cell surface, which is expected to reverse T-cell exhaustion
·No ADCR activity that mediates the secretion of IL-6 and IL-8 by macrophages, effectively avoiding the immunosuppressive effects of these cytokines
·Effectively induce the secretion of IL-2 and IFN-γ to kill tumor cells
③Safety: Deep Fc modification and unique inter-tumor enrichment effect
·IgG1 backbone antibody reduces host cell protein content, reducing the incidence of fevers and infusion reactions
·Completely eliminate ADCC, ADCP and CDC activities through Fc engineering, avoid T-cell depletion and immune adverse reactions caused by Fc-mediated immune cell activation
·Special multivalent binding ability ensures that antibodies are mainly distributed in tumor tissues with few in the periphery, thereby improving efficacy and reducing adverse reactions
Four aspects in innovation
Meet unmet medical need
As a product supported by China’s special “Major New Drug Development” program, Cadonilimab is China’s first immunotherapy drug approved for the treatment of advanced cervical cancer, as well as globally first dual immune checkpoint inhibitor bi-specific antibody to treat cancer.
Unique structure
Cadonilimab is designed as a novel tetrameric form, which could bind tetravalently to TILs co-expressing PD-1 & CTLA-4 with higher avidity, making it more likely to be enriched in tumor tissues after administration to continuously reduce the concentration of peripheral tissues and ensure better efficacy and safety.
First-in-class
The first approved dual immune checkpoint inhibitor drug in-house developed by Akeso with independent intellectual property rights. No similar drug with a similar mechanism of action has been approved worldwide before.
Better safety and efficacy
Cadonilimab shows better anti-tumor effects than therapies approved or recommended by international authoritative guidelines, and its safety profile is comparable to PD-1 monoclonal antibodies marketed abroad.
开坦尼® (Cadonilimab Injection)
Product information stated by NMPA in Approved Drug Catalog of China:
[Name]
Generic Name：Cadonilimab Injection
Brand Name：开坦尼®
English Name：Cadonilimab Injection
Chinese Pinyin：Kadunili Dankang Zhusheye
[Ingredients]
APIs：Cadonilimab (bi-specific recombinant humanized monoclonal antibody targeting PD-1 and CTLA-4).
Excipients：Histidine, histidine hydrochloride, sucrose, polysorbate 80 (II) and water for injection.
[Appearance]
This product is a colorless to pale yellow clear liquid, and may be slightly opalescent.
[Indications]
This product is indicated for the treatment of relapsed or metastatic cervical cancer (R/M CC) patients who progressed on or after platinum-based chemotherapy. This product is conditionally approved for marketing based on surrogate endpoints, and no clinical endpoint data has been obtained. The efficacy and safety of this product need to be further confirmed after marketing. Full approval for this indication will depend on ongoing confirmatory clinical trials demonstrating the clinical benefits of Cadonilimab.
[Specification]
125 mg (10 mL)/bottle
See Directions for Use for [Usage and Dosage], [Adverse Reactions], [Contraindications], [Precautions], etc.
Indications
Gastric cancer
Cervical cancer
Liver cancer
Other tumors
·A Phase III pivotal registration trial on Cadonilimab plus chemo as first-line trerapy for advanced gastric (G) or gastroesophageal junction cancer (GEJC) (marketed in China) ·A Phase Ib/II trial on Cadonilimab for the treatment of G/GEJC showed that:
Regardless of PD-L1 status
months
mOS
months
mPFS
12-month OS rate
ORR
DCR
Promising efficacy in population with high expression of PD-L1
CPS≥5
months
mOS
mPFS
Promising efficacy in population with low expression of PD-L1
CPS＜5
months
mOS
months
mPFS
Remarkable efficacy in the PD-L1 expression negative population
CPS＜1
months
mOS
months
mPFS
Source: ASCO 2023,abs#4031
Gastric cancer is one of the most common malignant tumors in the world and the third leading cause of cancer death worldwide. About 770,000 patients die of gastric cancer every year. The 5-year survival rate of advanced or metastatic gastric cancer is about 5–20%.
·Cadonilimab for the second-/third-line treatment of R/M cervical cancer (marketed in China)
Population-wide benefits
-
Regardless of PD-L1 expression
- 33.0%
ORR
- 3.75
months
mPFS
- 17.51
months
mOS
-
CPS ≥ 1 population
- 43.8%
ORR
- 6.34
months
mPFS
- not reached
mOS
·Cadonilimab for the first-line treatment of R/M cervical cancer
Population-wide benefits
-
Regardless of PD-L1 expression
- 79.3%
ORR
-
CPS ≥ 1 population
- 82.4%
ORR
-
CPS<1population
- 75.0%
ORR
·A registration/phase III trial of Cadonilimab combined with platinum-based chemotherapy +/- bevacizumab for the first-line treatment of R/M CC is ongoing
China has the second largest population of cervical cancer patients in the world, with 110,000 new cases in 2020.There is no standard treatment for R/M CC patients who has progressed on or after platinum-based chemotherapy, and monotherapy is a common clinical treatment option with limited efficacy and obvious toxicity. The approval of 开坦尼® addresses a huge unmet medical need for advanced cervical cancer in China.
China has the second largest population of cervical cancer patients in the world, with 110,000 new cases in 2020.There is no standard treatment for R/M CC patients who has progressed on or after platinum-based chemotherapy, and monotherapy is a common clinical treatment option with limited efficacy and obvious toxicity. The approval of 开坦尼® addresses a huge unmet medical need for advanced cervical cancer in China.
·A Phase III trial of Cadonilimab in adjuvant therapy after the radical resection of hepatocellular carcinoma at high risk of recurrence is ongoing
·A Phase II trial of Cadonilimab plus Lenvatinib for the first-line treatment of unresectable liver cancer showed that:
- 44.4%
ORR
- 77.8%
DCR
·A Phase Ib/II trial of Cadonilimab plus Lenvatinib and transcatheter arterial chemoembolization (TACE) for unresectable non-metastatic hepatocellular carcinoma is ongoing
Liver cancer is the third leading cause of cancer death worldwide. In 2020, there were 410,000 cases of liver cancer and 390,000 deaths in China. China has about 50% of the world’s liver cancer patients, and hepatocellular carcinoma (HCC) is the most important pathological type.
·More studies have been carried out on Cadonilimab treatment for renal cell carcinoma, non-small cell lung cancer, nasopharyngeal cancer, etc.