Retifanlimab

Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors.

• ZYNYZ is a programmed death receptor-1 (PD-1)–blocking antibody indicated: Squamous Cell Carcinoma of the Anal Canal (SCAC) in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). ( 1.1 ) as a single agent for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy.

• None. None.contraindicated

Administer ZYNYZ as an intravenous infusion over 30 minutes after dilution ( 2.3 ): For Squamous Cell Carcinoma of the Anal Canal (SCAC), in combination with carboplatin and paclitaxel, or as a single agent ( 2.1 ): 500 mg every 4 weeks, or 375 mg every 3 weeks For Merkel Cell Carcinoma (MCC) ( 2.1 ): 500 mg every 4 weeks See full prescribing information for dosage modifications for adverse reactions ( 2.2 ) and preparation and administration instructions. ( 2.3 ) 2.1 Recommended Dosage The recommended dosages of ZYNYZ are provided in Table 1. Administer ZYNYZ as an intravenous infusion after dilution, over 30 minutes, as recommended [see Dosage and Administration ( 2.3 )] . Table 1: Recommended Dosage of ZYNYZ Indication Recommended Dosage of ZYNYZ Duration of Treatment Combination Therapy Refer to the Prescribing Information for the agents administered in combination with ZYNYZ for recommended dosing information, as appropriate.

Immune-Mediated Adverse Reactions ( 5.1 ) Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune‑mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, and immune‑mediated dermatologic adverse reactions, and solid organ transplant rejection. Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue ZYNYZ and administer corticosteroids based on the severity of reaction. ( 2.2 ) Infusion-Related Reactions: Interrupt, slow the rate of infusion, or permanently discontinue ZYNYZ based on severity of reaction. ( 2.2 , 5.2 ) Complications of Allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD‑1/PD‑L1–blocking antibody. ( 5.3 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception.

The following adverse reactions are described elsewhere in the labeling. Severe and Fatal Immune-Mediated Adverse Reactions [see Warnings and Precautions ( 5.1 )] Infusion-Related Reactions [see Warnings and Precautions ( 5.2 )] Complications of Allogeneic HSCT [see Warnings and Precautions ( 5.3 )] ZYNYZ in Combination with Carboplatin and Paclitaxel In patients with SCAC, the most common (≥ 20%) adverse reactions are fatigue, peripheral neuropathy, nausea, alopecia, diarrhea, musculoskeletal pain, constipation, hemorrhage, rash, vomiting, decreased appetite, pruritus, and abdominal pain. ( 6.1 ) ZYNYZ as a Single Agent In patients with SCAC, the most common (≥ 10%) adverse reactions are fatigue, musculoskeletal pain, diarrhea, non-urinary tract infections, perineal pain, hemorrhage, urinary tract infection, rash, nausea, decreased appetite, constipation, abdominal pain, dyspnea, pyrexia, vomiting, cough, pruritus, hypothyroidism, headache, and decreased weight. ( 6.1 ) In patients with MCC, the most common (≥ 10%) adverse reactions are musculoskeletal pain, fatigue, pruritus, diarrhea, rash, pyrexia, nausea, and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Incyte Corporation at 1-855-463-3463 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Lactation: Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action, ZYNYZ can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data on the use of ZYNYZ in pregnant women. Animal studies have demonstrated that inhibition of the PD‑1/PD‑L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death ( see Data ). Human IgG4 immunoglobulins (IgG4) are known to cross the placenta; therefore, retifanlimab-dlwr has the potential to be transmitted from the mother to the developing fetus. Advise women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Animal reproduction studies have not been conducted with ZYNYZ to evaluate its effect on reproduction and fetal development. A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus.

Metabolism

The pharmacokinetics of retifanlimab-dlwr were evaluated in patients with various solid tumors, including patients with SCAC and patients with MCC. Retifanlimab-dlwr exposures (maximum concentration [C max ] and area under the curve [AUC]) increased proportionally over a dosage range from 375 mg to 750 mg (0.75- to 1.5-fold of the approved recommended dose).

• Mar 22, 2023BLABLA761334Incyte Corp

1. 1Off Label Use1335%
2. 2Disease Progression411%
3. 3Anal Cancer38.1%
4. 4Malignant Neoplasm Progression38.1%
5. 5Condition Aggravated25.4%
6. 6Death25.4%
7. 7Nasopharyngitis25.4%
8. 8Nausea25.4%
9. 9Neuropathy Peripheral25.4%
10. 10Neutropenia25.4%
11. 11Therapy Cessation25.4%
12. 12Thrombocytopenia25.4%
13. 13Anaemia12.7%
14. 14Anal Squamous Cell Carcinoma12.7%
15. 15Arthralgia12.7%

The 10 most recently updated of 59 ClinicalTrials.gov registrations naming Retifanlimab as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• ctHPVDNA Response-Adapted Chemoradiation +/- Retifanlimab Treatment in Locally-Advanced Anal Cancer
  Not yet recruiting · Phase 2 · Interventional · 33 enrolled · Jennifer Dorth
  NCT07425054updated 2026-06-12
• Safety and Efficacy of Retifanlimab (INCMGA00012) Alone or in Combination With Other Therapies in Participants With Advanced or Metastatic Endometrial Cancer Who Have Progressed on or After Platinum-based Chemotherapy.
  Completed · Phase 2 · Interventional · 206 enrolled · Incyte Corporation
  NCT04463771updated 2026-06-11
• Phase I/II Study of the Combination Immunotherapy Regimen: SX-682, TriAdeno Vaccine, Retifanlimab and IL-15 Agonist N-803 (STAR15) for Metastatic Colorectal Cancer (mCRC)
  Recruiting · Phase 1 · Phase 2 · Interventional · 60 enrolled · National Cancer Institute (NCI)
  NCT06149481updated 2026-06-05
• ASTX727 & Retifanlimab-dlwr for Advanced Merkel Cell After Progression on Anti-PD-(L)1
  Not yet recruiting · Phase 1 · Phase 2 · Interventional · 31 enrolled · University of Wisconsin, Madison
  NCT07472322updated 2026-05-29
• A Phase Ib Study of Novel Combination (New) of Low Dose Oral CyclophoSphamide (s) to Potentiate Axatilimab (A) + Retifanlimab (R) in Treating Metastatic Triple Negative Breast Cancer (TNBC)
  Recruiting · Phase 1 · Interventional · 24 enrolled · M.D. Anderson Cancer Center
  NCT06959537updated 2026-05-20
• Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
  Recruiting · Phase 2 · Interventional · 109 enrolled · Scott R. Plotkin, MD, PhD
  NCT04374305updated 2026-05-06
• A Study to Evaluate INCB161734 in Participants With Advanced or Metastatic Solid Tumors With KRAS G12D Mutation
  Recruiting · Phase 1 · Interventional · 710 enrolled · Incyte Corporation
  NCT06179160updated 2026-05-04
• Neoantigen-based Personalized DNA Vaccine With Retifanlimab PD-1 Blockade Therapy in Patients With Newly Diagnosed, Unmethylated Glioblastoma
  Active not recruiting · Phase 1 · Interventional · 27 enrolled · Washington University School of Medicine
  NCT05743595updated 2026-05-04
• Neoadjuvant Chemotherapy and Retifanlimab in Patients With Selected Sarcomas (TORNADO)
  Active not recruiting · Phase 2 · Interventional · 66 enrolled · Institut Bergonié
  NCT04968106updated 2026-04-21
• A Trial to Evaluate CSF ctDNA and Safety of Plixorafenib Alone or With Retifanlimab in Patients With BRAF-altered Glioma
  Recruiting · Early phase 1 · Interventional · 24 enrolled · Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  NCT06610682updated 2026-04-16

Frequently asked questions

How does Retifanlimab work?

Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors.

What is Retifanlimab used for?

According to FDA labeling, Retifanlimab carries indications including: ZYNYZ is a programmed death receptor-1 (PD-1)–blocking antibody indicated: Squamous Cell Carcinoma of the Anal Canal (SCAC) in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal (SCAC). ( 1.1 ) as a single agent for the treatment of adult patients with locally recurrent or metastatic SCAC with disease progression on or intolerance to platinum-based chemotherapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Retifanlimab?

Retifanlimab is classified as PD-1/PD-L1 (Programmed cell death protein 1/death ligand 1) inhibitors, Programmed Death Receptor-1 Blocking Antibody, Programmed Death Receptor-1-directed Antibody Interactions, Cellular Proliferation Alteration, Decreased Cytokine Production, Decreased T Lymphocyte Activation.

What are the brand names for Retifanlimab?

Retifanlimab is marketed under brand names including Zynyz.

What are the contraindications for Retifanlimab?

Retifanlimab labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.