Cadonilimab (AK-104)
Mechanism of action
From the NCI Drug Dictionary: A bispecific antibody directed against the human negative immunoregulatory checkpoint receptors programmed cell death protein 1 (PD-1; PDCD1; CD279) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA4; CTLA-4), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, cadonilimab targets and binds to both PD-1 and CTLA4 expressed on tumor-infiltrating T lymphocytes (TILs), and inhibits the PD-1- and CTLA4-mediated downregulation of T-cell activation and proliferation. This restores immune function and activates a sustained cytotoxic T-lymphocyte (CTL)-mediated immune response against tumor cells. Both PD-1 and CTLA4 are selectively expressed on TILs in the tumor microenvironment (TME) and negatively regulate the activation and effector functions of T-cells. They play key roles in the downregulation of the immune system and tumor evasion from host immunity. Dual checkpoint blockade of PD1 and CTLA4 with cadonilimab may enhance T-cell activation and proliferation more than the blockade of either immune checkpoint receptor alone.
Diseases for which it is used
History of changes in NMPA indication
- 2022-06-29: Initial approval for use in patients with relapsed or metastatic cervical cancer (r/mCC) who have progressed on or after platinum-based chemotherapy. (Based on COMPASSION-13)
- 2024-09-30: Approved in combination with fluoropyrimidine and platinum-based chemotherapy for first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. (Based on COMPASSION-15)
Also known as
- Code name: AK-104