Dostarlimab
Identification
- Summary
Dostarlimab is an anti-PD-1 monoclonal antibody used in the treatment of mismatch repair deficient endometrial cancers and solid tumours with no alternative treatment options.
- Brand Names
- Jemperli
- Generic Name
- Dostarlimab
- DrugBank Accession Number
- DB15627
- Background
Dostarlimab is an IgG4 humanized monoclonal antibody targeted against the human programmed death receptor-1 (PD-1).6 PD-1 receptors are found on T-cells and, when activated, serve to inhibit immune responses - some cancers leverage this system by overexpressing PD-1 ligands, thereby effectively inhibiting the anti-tumor immune response that would typically attempt to destroy the cancerous cells.3 Agents acting on the PD-1 pathway, such as nivolumab and pembrolizumab, facilitate endogenous immune-mediated anti-tumor activity and may therefore be used to treat a wide variety of cancers, including those of the skin, lung, kidneys, and liver.
In April 2021, dostarlimab was granted accelerated approval by the FDA - as GlaxoSmithKline's dostarlimab-gxly (Jemperli) - for the treatment of adult patients with recurrent or advanced mismatch repair deficient (dMMR) endometrial cancer experiencing disease progression despite treatment with platinum-containing chemotherapy regimens.7 A companion diagnostic device - the VENTANA MMR RxDx Panel - was also approved alongside this indication to select appropriate patients for treatment.7 This indication was granted full FDA approval on February 10, 2023.10 Dostarlimab-gxly was granted second accelerated approval for the treatment of solid tumours in the same month.9
Dostarlimab is currently under investigation for the treatment of rectal cancers with mismatch repair deficiency. A prospective phase II study in patients with mismatch repair-deficient locally advanced rectal cancer resulted in all twelve patients exhibiting a complete clinical response.5
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6420H9832N1680O2014S44
- Protein Average Weight
- 144000.0 Da (non-glycosylated)
- Sequences
>Heavy Chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYDMSWVRQAPGKGLEWVSTISGGGSYTYY QDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASPYYAMDYWGQGTTVTVSSASTK GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFP PKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNHYTQKSLSLSLGK
>Light Chain DIQLTQSPSFLSAYVGDRVTITCKASQDVGTAVAWYQQKPGKAPKLLIYWASTLHTGVPS RFSGSGSGTEFTLTISSLQPEDFATYYCQHYSSYPWTFGQGTKLEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA FormatReferences:
- Statement on a Nonproprietary Name Adopted by the USAN Council: Dostarlimab [Link]
- Synonyms
- Dostarlimab
- dostarlimab-gxly
- Immunoglobulin G4, anti-programmed cell death protein 1 (PDCD1) (humanized clone ABT1 gamma4-chain), disulfide with humanized clone ABT1 kappa-chain, dimer
- External IDs
- GSK-4057190
- GSK4057190
- TSR 042
- TSR-042
- WBP-285
Pharmacology
- Indication
Dostarlimab is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer that has progressed despite ongoing or prior treatment with a platinum-containing chemotherapy regimen. It is used as monotherapy or in combination with carboplatin and paclitaxel.6,11,12,13
It is also indicated for the treatment of dMMR recurrent or advanced solid tumors in adults, as determined by an FDA-approved test, that have progressed on or following prior treatment and in patients who have no satisfactory alternative treatment options. This indication is approved under accelerated approval, and continued approval for this indication may be contingent upon verification and description of and description of clinical benefit in confirmatory trials.9
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Advanced microsatellite instability high endometrial carcinoma Regimen in combination with: Paclitaxel (DB01229), Carboplatin (DB00958) •••••••••••• ••••• ••••••••• Used in combination to treat Advanced mismatch repair-deficient (dmmr) endometrial cancer Regimen in combination with: Paclitaxel (DB01229), Carboplatin (DB00958) •••••••••••• ••••• ••••••••• Treatment of Advanced mismatch repair-deficient (dmmr) endometrial cancer •••••••••••• ••••• ••••••• ••• •••••••••• •••••• •• ••••••••• ••••••••••••••••••• ••••••••••••• ••• • ••••••••• ••• •••••••• ••••••• •• ••••••••• ••••••••• Treatment of Advanced mismatch repair deficient (dmmr) solid tumors •••••••••••• ••••• •••••••••• ••••••••••• ••••••••• •••••••• ••••••• ••••••••••• ••••• •••••••• ••••••••• ••••••••• Used in combination to treat Recurrent microsatellite instability (msi)-high endometrial cancer Regimen in combination with: Paclitaxel (DB01229), Carboplatin (DB00958) •••••••••••• ••••• ••••••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Dostarlimab is an immunotherapy that facilitates the body's endogenous anti-tumor immune response in the treatment cancer.6 It is administered over a span of 30 minutes via intravenous infusion every three to six weeks depending on the cycle.6
Agents that interfere with the PD-1/PD-L1 pathway, including dostarlimab, remove an important immune system inhibitory response and may therefore induce immune-mediated adverse reactions which can be severe or fatal. These reactions can occur in any organ system and can occur at any time after starting therapy, and while they most often manifest during therapy they may also appear after discontinuing the causative agent. Patients receiving therapy with dostarlimab should be monitored closely for evidence of an underlying immune-mediated reaction and evaluated and treated promptly if an immune-mediated reaction is suspected.6
- Mechanism of action
Approximately 13-30% of recurrent endometrial cancers involve microsatellite instability (MSI) or mismatch repair deficiency (dMMR).3,4 The mutations resulting in dMMR endometrial cancers are primarily somatic in nature (~90%), although 5-10% of cases involve germline mutations.4 Cancers that have mutations resulting in dMMR can upregulate the expression of programmed death receptor-1 (PD-1) ligands 1 and 2 (PD-L1 and -L2) - PD-1 is found on T-cells and, when activated, inhibits their proliferation and the production of cytokines.6 The binding of these ligands to PD-1 thereby functions as an immune checkpoint that downregulates the anti-tumor immune response.3
Dostarlimab is a monoclonal antibody targeted against PD-1 - it binds to the receptor and prevents interactions with PD-L1 and PD-L2, thus allowing the anti-tumor immune response to proceed unimpeded.6
Target Actions Organism AProgrammed cell death protein 1 binderantibodyHumans - Absorption
During the first cycle, and administered at 500mg intravenously every 3 weeks, the mean Cmax and AUC0-tau of dostarlimab-gxly are 171 mcg/mL and 35,730 mcg.h/mL, respectively. When administered at 1000mg every 6 weeks, the mean Cmax and AUC0-tau are 309 mcg/mL and 95,820 mcg.h/mL, respectively.6
- Volume of distribution
At steady-state, the mean volume of distribution of dostarlimab is 5.3L.6
- Protein binding
Not Available
- Metabolism
The metabolism of dostarlimab has not been characterized, but it is expected to be degraded via catabolic pathways into smaller peptides and amino acids.6,2
- Route of elimination
Not Available
- Half-life
The mean terminal elimination half-life of dostarlimab is 25.4 days.6
- Clearance
At steady-state, the mean clearance of dostarlimab is 0.007 L/h.6
- Adverse Effects
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- Toxicity
There are no data regarding overdose with dostarlimab. Symptoms of overdosage are likely to be consistent with the adverse effect profile of dostarlimab and may therefore involve significant immune-mediated reactions.6
- 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 softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Dostarlimab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Dostarlimab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Dostarlimab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Dostarlimab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Dostarlimab. - 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.
- International/Other Brands
- Jemperli (GlaxoSmithKline)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Jemperli Injection 50 mg/1mL Intravenous GlaxoSmithKline LLC 2021-04-22 Not applicable US Jemperli Injection, solution, concentrate 500 mg Intravenous Glaxo Smith Kline (Ireland) Limited 2022-06-06 Not applicable EU Jemperli Solution 50 mg / mL Intravenous Glaxosmithkline Inc 2022-02-22 Not applicable Canada
Categories
- ATC Codes
- L01FF07 — Dostarlimab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Anions
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Electrolytes
- Globulins
- Hydrogen Sulfide
- Immune Checkpoint Inhibitors
- Immunoglobulins
- Immunoproteins
- Ions
- 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
- Programmed Death Receptor-1-directed Antibody Interactions
- Proteins
- Serum Globulins
- Sulfides
- Sulfur Compounds
- 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
- P0GVQ9A4S5
- CAS number
- 2022215-59-2
References
- General References
- Kaplon H, Muralidharan M, Schneider Z, Reichert JM: Antibodies to watch in 2020. MAbs. 2020 Jan-Dec;12(1):1703531. doi: 10.1080/19420862.2019.1703531. [Article]
- Temrikar ZH, Suryawanshi S, Meibohm B: Pharmacokinetics and Clinical Pharmacology of Monoclonal Antibodies in Pediatric Patients. Paediatr Drugs. 2020 Apr;22(2):199-216. doi: 10.1007/s40272-020-00382-7. [Article]
- Green AK, Feinberg J, Makker V: A Review of Immune Checkpoint Blockade Therapy in Endometrial Cancer. Am Soc Clin Oncol Educ Book. 2020 Mar;40:1-7. doi: 10.1200/EDBK_280503. [Article]
- Deshpande M, Romanski PA, Rosenwaks Z, Gerhardt J: Gynecological Cancers Caused by Deficient Mismatch Repair and Microsatellite Instability. Cancers (Basel). 2020 Nov 10;12(11). pii: cancers12113319. doi: 10.3390/cancers12113319. [Article]
- Cercek A, Lumish M, Sinopoli J, Weiss J, Shia J, Lamendola-Essel M, El Dika IH, Segal N, Shcherba M, Sugarman R, Stadler Z, Yaeger R, Smith JJ, Rousseau B, Argiles G, Patel M, Desai A, Saltz LB, Widmar M, Iyer K, Zhang J, Gianino N, Crane C, Romesser PB, Pappou EP, Paty P, Garcia-Aguilar J, Gonen M, Gollub M, Weiser MR, Schalper KA, Diaz LA Jr: PD-1 Blockade in Mismatch Repair-Deficient, Locally Advanced Rectal Cancer. N Engl J Med. 2022 Jun 5. doi: 10.1056/NEJMoa2201445. [Article]
- FDA Approved Drug Products: Jemperli (dostarlimab-gxly) for intravenous injection [Link]
- FDA News Release: FDA grants accelerated approval to dostarlimab-gxly for dMMR endometrial cancer [Link]
- Statement on a Nonproprietary Name Adopted by the USAN Council: Dostarlimab [Link]
- FDA Approved Drug Products: JEMPERLI (dostarlimab-gxly) injection, for intravenous use (February 2023) [Link]
- BioSpace: US FDA grants regular approval for Jemperli for the treatment of patients with recurrent or advanced mismatch repair-deficient endometrial cancer [Link]
- FDA Approved Drug Products: JEMPERLI (dostarlimab-gxly) injection, for intravenous use (July 2023) [Link]
- Health Canada Approved Drug Products: JEMPERLI (dostarlimab) Intravenous Solution for Infusion [Link]
- EMA Approved Drug Products: JEMPERLI (dostarlimab) Intravenous Infusion [Link]
- External Links
- 2539967
- Wikipedia
- Dostarlimab
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 Neoplasm 1 3 Active Not Recruiting Treatment Ovarian Neoplasms / Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma 1 3 Recruiting Treatment Colon Neoplasm / Neoplasms, Colon 1 3 Recruiting Treatment Endometrial Cancer 1 3 Recruiting Treatment Ovarian Cancer 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 50 mg/1mL Injection, solution Intravenous 500 MG Injection, solution, concentrate Intravenous 500 mg Solution Intravenous 50 mg / mL - 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
- BinderAntibody
- 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
- FDA Approved Drug Products: Jemperli (dostarlimab-gxly) for intravenous injection [Link]
Drug created at March 07, 2020 19:58 / Updated at February 14, 2024 00:55