retifanlimab — Drug Monograph
Brand names: Zynyz
Drug class: Checkpoint Inhibitor
Mechanism of Action
Retifanlimab is a humanized IgG4 monoclonal antibody that binds to the programmed death-1 (PD-1) receptor on T cells, blocking its interaction with the ligands PD-L1 and PD-L2. This blockade prevents PD-1-mediated inhibitory signaling, thereby restoring T-cell activation and proliferative capacity. The resulting enhancement of cytotoxic T-lymphocyte activity promotes immune-mediated tumor cell killing. Retifanlimab also inhibits regulatory T-cell activity within the tumor microenvironment, further augmenting anti-tumor immune responses.
FDA Indications
- MSI-H/dMMR advanced or recurrent endometrial carcinoma, first-line in combination with carboplatin and paclitaxel (approved March 2023; RUBY trial)
- Advanced Merkel cell carcinoma (approved March 2023)
- Locally advanced squamous cell anal carcinoma (SCAC) in combination with carboplatin and paclitaxel (approved March 2023; POD1UM-303/InterAACT2 trial)
Common Side Effects
- Fatigue (≥10%)
- Nausea
- Alopecia (when used with chemotherapy)
- Peripheral neuropathy (combination regimen)
- Constipation
- Musculoskeletal pain
- Decreased appetite
- Rash
- Anemia
- Neutropenia (combination regimen)
- Thrombocytopenia (combination regimen)
- Increased AST/ALT
Clinical Pearl
In the RUBY trial, the addition of retifanlimab to carboplatin/paclitaxel significantly improved PFS in MSI-H/dMMR endometrial carcinoma (HR 0.30), making biomarker testing at diagnosis essential for all advanced endometrial cancers. Unlike some other PD-1 inhibitors, retifanlimab's every-4-week dosing schedule simplifies administration logistics in the maintenance phase. Clinicians should maintain a low threshold for immune-mediated adverse event workup, particularly thyroid dysfunction and…
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