Retifanlimab
Identification
- Summary
Retifanlimab is a PD-1–blocking antibody indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma.
- Brand Names
- Zynyz
- Generic Name
- Retifanlimab
- DrugBank Accession Number
- DB15766
- Background
Retifanlimab is a humanized IgG4 kappa monoclonal antibody that binds to the programmed death receptor-1 (PD-1), blocking PD-1 interaction with its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). By blocking the PD-1/PD-L1/2 pathway, retifanlimab potentiates T-cell activity and boosts the immune response against cancer cells.3 Other monoclonal antibodies that block PD-1 include pembrolizumab, nivolumab and cemiplimab.
On October 2021, Incyte Biosciences withdrew its application for a marketing authorization of retifanlimab for the treatment of squamous carcinoma of the anal canal.4,6 On March 2023, the FDA granted accelerated approval to retifanlimab for a different indication, the treatment of metastatic or recurrent locally advanced Merkel cell carcinoma (MCC).3,5 The use of retifanlimab in combination with other oncology drugs for the treatment of metastatic gastroesophageal adenocarcinoma has also been evaluated.1,2
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6456H9934N1702O2032S46
- Protein Average Weight
- 148000.0 Da (approximate)
- Sequences
>Retifanlimab_Heavy_chain QVQLVQSGAEVKKPGASVKVSCKASGYSFTSYWMNWVRQAPGQGLEWIGVIHPSDSETWL DQKFKDRVTITVDKSTSTAYMELSSLRSEDTAVYYCAREHYGTSPFAYWGQGTLVTVSSA STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVF LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN VFSCSVMHEALHNHYTQKSLSLSLG
>Retifanlimab_Light_chain EIVLTQSPATLSLSPGERATLSCRASESVDNYGMSFMNWFQQKPGQPPKLLIHAASNQGS GVPSRFSGSGSGTDFTLTISSLEPEDFAVYFCQQSKEVPYTFGGGTKVEIKRTVAAPSVF IFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLS STLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA FormatReferences:
- WHO: International Nonproprietary Names for Pharmaceutical Substances (INN) - List 83 [Link]
- Synonyms
- Anti-PD-1 monoclonal antibody MGA012
- Retifanlimab
- External IDs
- AEX-1188
- AEX1188
- INCMGA-00012
- INCMGA00012
- MGA-012
- MGA012
- WHO 11095
Pharmacology
- Indication
Retifanlimab is indicated for the treatment of adult patients with metastatic or recurrent locally advanced Merkel cell carcinoma.3
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Metastatic locally advanced merkel cell carcinoma •••••••••••• ••••• ••••••••• Treatment of Recurrent, locally advanced merkel cell carcinoma •••••••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
The exposure-response relationship and time course of pharmacodynamic response for safety and effectiveness of retifanlimab have not been fully characterized.3 Since retifanlimab targets the programmed death receptor-1 (PD-1) and blocks the PD-1/PD-ligand 1 (PD-L1) pathways, it has the potential to induce immune-mediated adverse reactions. The use of retifanlimab may lead to the development of immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, and other immune-mediated adverse reactions. The use of retifanlimab has also been associated to infusion-related reactions, serious complications during allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.3
- Mechanism of action
Retifanlimab is a programmed death receptor-1 (PD-1)–blocking antibody that potentiates T-cell activity and boosts the immune response against cancer cells. PD-1 is found on the surface of T-cells, and when it binds to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2), it inhibits T-cell proliferation and cytokine production. In normal conditions, cells produce PD-L1 and PD-L2 to maintain self-tolerance and ensure that the immune system does not attack health cells. However, in certain types of cancers, PD-L1 and PD-L2 are upregulated, contributing to a lower active T-cell immune surveillance of tumors. Retifanlimab binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2. By preventing the activation of this inhibitory pathway, retifanlimab promotes immune reactivity and enhances anti-tumor immune response.3
Target Actions Organism AProgrammed cell death protein 1 antibodyblockerHumans - Absorption
The pharmacokinetics of retifanlimab were assessed in patients with different types of solid tumors, including Merkel cell carcinoma (MCC). From 375 mg to 750 mg (0.75- to 1.5-fold of the approved recommended dose), the Cmax and AUC of retifanlimab increased in a dose-proportional manner. In patients given 500 mg of retifanlimab every 4 weeks, steady-state concentrations are reached at cycle 6 (approximately 6 months) with a 1.3-fold systemic accumulation.3 Factors such as age, sex, body weight, race, albumin level, renal function and mild hepatic impairment did not have a clinically significant effect on the pharmacogenetic profile of retifanlimab. The pharmacokinetics of retifanlimab have not been evaluated in patients with moderate or severe hepatic impairment.3
- Volume of distribution
At steady-state, retifanlimab has a mean volume of distribution of 6.0 L.3
- Protein binding
Not Available
- Metabolism
As a monoclonal antibody, retifanlimab is expected to be metabolized by proteases throughout the body.
- Route of elimination
No excretion studies were performed since, as an antibody, retifanlimab is degraded to small peptides and amino acids.4
- Half-life
At steady-state, retifanlimab has an elimination half-life of 19 days.3
- Clearance
Following the first dose of retifanlimab, clearance was 0.31 L/day, which decreased by approximately 23% over time. The steady-state clearance of retifanlimab was 0.24 L/day.3
- Adverse Effects
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- Toxicity
Toxicity information regarding retifanlimab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects, such as severe and fatal immune-mediated adverse reactions and severe infusion-related reactions.3 Symptomatic and supportive measures are recommended. The carcinogenicity and genotoxicity of retifanlimab have not been evaluated in non-clinical studies. In monkeys given 1-month and 3-month repeat doses, retifanlimab did not lead to no notable effects in the male and female reproductive organs; however, most animals were not sexually mature.3
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbroxol The risk or severity of methemoglobinemia can be increased when Retifanlimab is combined with Ambroxol. Articaine The risk or severity of methemoglobinemia can be increased when Retifanlimab is combined with Articaine. Benzocaine The risk or severity of methemoglobinemia can be increased when Retifanlimab is combined with Benzocaine. Benzyl alcohol The risk or severity of methemoglobinemia can be increased when Retifanlimab is combined with Benzyl alcohol. Bupivacaine The risk or severity of methemoglobinemia can be increased when Retifanlimab is combined with Bupivacaine. - Food Interactions
- No interactions found.
Products
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Zynyz Injection 25 mg/1mL Intravenous Incyte Corporation 2023-03-22 Not applicable US
Categories
- ATC Codes
- L01FF10 — Retifanlimab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Immune Checkpoint Inhibitors
- Immunoglobulins
- MONOCLONAL ANTIBODIES AND ANTIBODY DRUG CONJUGATES
- PD-1/PDL-1 (Programmed cell death protein 1/death ligand 1) inhibitors
- Programmed Death Receptor-1 Blocking Antibody
- Proteins
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- 2Y3T5IF01Z
- CAS number
- 2079108-44-2
References
- General References
- Rao S, Jones M, Bowman J, Tian C, Spano JP: POD1UM-303/InterAACT 2: A phase III, global, randomized, double-blind study of retifanlimab or placebo plus carboplatin-paclitaxel in patients with locally advanced or metastatic squamous cell anal carcinoma. Front Oncol. 2022 Aug 24;12:935383. doi: 10.3389/fonc.2022.935383. eCollection 2022. [Article]
- Catenacci DVT, Kang YK, Yoon HH, Shim BY, Kim ST, Oh DY, Spira AI, Ulahannan SV, Avery EJ, Boland PM, Chao J, Chung HC, Gardner F, Klempner SJ, Lee KW, Oh SC, Peguero J, Sonbol MB, Shen L, Moehler M, Sun J, Li D, Rosales MK, Park H: Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A. ESMO Open. 2022 Oct;7(5):100563. doi: 10.1016/j.esmoop.2022.100563. Epub 2022 Aug 24. [Article]
- FDA Approved Drug Products: ZYNYZ (retifanlimab-dlwr) injection, for intravenous use (March 2023) [Link]
- EMA Withdrawal Assessment Report: Zynyz (retifanlimab) [Link]
- US Food & Drug Administration: FDA grants accelerated approval to retifanlimab-dlwr for metastatic or recurrent locally advanced Merkel cell carcinoma [Link]
- EMA: Withdrawal of application for the marketing authorisation of Zynyz (retifanlimab) [Link]
- External Links
- 2632981
- Wikipedia
- Retifanlimab
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Anal Squamous Cell Carcinoma 1 3 Active Not Recruiting Treatment Metastatic Non-squamous Non Small Cell Lung Cancer / Metastatic squamous cell cancer Non-small cell lung cancer 1 3 Recruiting Treatment Breast Cancer / Breast Neoplasms / End Stage Cancer / Metastatic Breast Cancer 1 3 Withdrawn Treatment Non-Small Cell Lung Cancer (NSCLC) 1 2 Active Not Recruiting Treatment Advanced Malignant Neoplasm 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 25 mg/1mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- AntibodyBlocker
- General Function
- Signal transducer activity
- Specific Function
- Inhibitory cell surface receptor involved in the regulation of T-cell function during immunity and tolerance. Upon ligand binding, inhibits T-cell effector functions in an antigen-specific manner. ...
- Gene Name
- PDCD1
- Uniprot ID
- Q15116
- Uniprot Name
- Programmed cell death protein 1
- Molecular Weight
- 31646.635 Da
References
- Rao S, Jones M, Bowman J, Tian C, Spano JP: POD1UM-303/InterAACT 2: A phase III, global, randomized, double-blind study of retifanlimab or placebo plus carboplatin-paclitaxel in patients with locally advanced or metastatic squamous cell anal carcinoma. Front Oncol. 2022 Aug 24;12:935383. doi: 10.3389/fonc.2022.935383. eCollection 2022. [Article]
- Catenacci DVT, Kang YK, Yoon HH, Shim BY, Kim ST, Oh DY, Spira AI, Ulahannan SV, Avery EJ, Boland PM, Chao J, Chung HC, Gardner F, Klempner SJ, Lee KW, Oh SC, Peguero J, Sonbol MB, Shen L, Moehler M, Sun J, Li D, Rosales MK, Park H: Margetuximab with retifanlimab as first-line therapy in HER2+/PD-L1+ unresectable or metastatic gastroesophageal adenocarcinoma: MAHOGANY cohort A. ESMO Open. 2022 Oct;7(5):100563. doi: 10.1016/j.esmoop.2022.100563. Epub 2022 Aug 24. [Article]
- FDA Approved Drug Products: ZYNYZ (retifanlimab-dlwr) injection, for intravenous use (March 2023) [Link]
- EMA Withdrawal Assessment Report: Zynyz (retifanlimab) [Link]
Drug created at August 20, 2020 19:21 / Updated at March 25, 2023 04:38