Anti-programmed Cell Death Protein 1 (PDCD1) (humanized Clone ABT1 Gamma4-chain)
Anti-programmed Cell Death Protein 1 (PDCD1) (humanized Clone ABT1 Gamma4-chain) Uses, Dosage, Side Effects, Food Interaction and all others data.
Anti-programmed Cell Death Protein 1 (PDCD1) (humanized Clone ABT1 Gamma4-chain) is an IgG4 humanized monoclonal antibody targeted against the human programmed death receptor-1 (PD-1). 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. 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 an 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. As this accelerated approval was granted only for the treatment of dMMR endometrial cancers, it was approved alongside a companion diagnostic device - the VENTANA MMR RxDx Panel - for use in selecting appropriate patients for treatment.
Anti-programmed Cell Death Protein 1 (PDCD1) (humanized Clone ABT1 Gamma4-chain) is an immunotherapy that facilitates the body's endogenous anti-tumor immune response in the treatment cancer. It is administered over a span of 30 minutes via intravenous infusion every three to six weeks depending on the cycle.
Table Of contents
- Anti-programmed Cell Death Protein 1 (PDCD1) (humanized Clone ABT1 Gamma4-chain)
- Uses
- Dosage
- Side Effect
- Precautions
- Interactions
- Uses during Pregnancy
- Uses during Breastfeeding
- Accute Overdose
- Food Interaction
- Half Life
- Volume of Distribution
- Clearance
- Interaction With other Medicine
- Contradiction
- Storage
| Trade Name | Anti-programmed Cell Death Protein 1 (PDCD1) (humanized Clone ABT1 Gamma4-chain) |
| Availability | Prescription only |
| Generic | Dostarlimab |
| Dostarlimab Other Names | 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 |
| Related Drugs | methotrexate, Keytruda, medroxyprogesterone, megestrol, hydroxyurea, pembrolizumab, Provera, Lenvima, Hydrea, Jemperli |
| Type | |
| Formula | C6420H9832N1680O2014S44 |
| Weight | 144000.0 Da (non-glycosylated) |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Anti-programmed Cell Death Protein 1 (PDCD1) (humanized Clone ABT1 Gamma4-chain) is an anti-PD-1 monoclonal antibody used in the treatment of mismatch repair deficient endometrial cancers.
Anti-programmed Cell Death Protein 1 (PDCD1) (humanized Clone ABT1 Gamma4-chain)-gxly 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.
Anti-programmed Cell Death Protein 1 (PDCD1) (humanized Clone ABT1 Gamma4-chain) is also used to associated treatment for these conditions: Advanced Mismatch Repair-deficient (dMMR) Endometrial Cancer, Recurrent Mismatch Repair-deficient (dMMR) Endometrial Cancer
How Anti-programmed Cell Death Protein 1 (PDCD1) (humanized Clone ABT1 Gamma4-chain) works
Approximately 13-30% of recurrent endometrial cancers involve microsatellite instability (MSI) or mismatch repair deficiency (dMMR). The mutations resulting in dMMR endometrial cancers are primarily somatic in nature (~90%), although 5-10% of cases involve germline mutations. 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. The binding of these ligands to PD-1 thereby functions as an immune checkpoint that downregulates the anti-tumor immune response.
Anti-programmed Cell Death Protein 1 (PDCD1) (humanized Clone ABT1 Gamma4-chain) 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.
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.
Food Interaction
No interactions found.Volume of Distribution
At steady-state, the mean volume of distribution of dostarlimab is 5.3L.
Elimination Route
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.
Half Life
The mean terminal elimination half-life of dostarlimab is 25.4 days.
Clearance
At steady-state, the mean clearance of dostarlimab is 0.007 L/h.
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