3. DOSTARLIMAB
ï” Dostarlimab is a programmed death receptor-1 (PD-1)âblocking monoclonal
antibody.
ï” Is an antineoplastic agent
ï” Recently approved in treatment of endometrial cancer and colorectal cancer
4. PHARMAKOKINETICS
ï” The mean terminal elimination half-life of dostarlimab is 25.4 days.
ï” Route of administration â IV
ï” Dose - 1-4 doses: 500 mg IV q3Weeks, then Dose 5 and thereafter (start 3
weeks after Dose 4): 1,000 mg IV q6Weeks until disease progression or
unacceptable toxicity
ï” Diluted in NS or 5%D and administed as slow IV infusion over 30 mins
ï” Cost- 3.40 lakhs
5. MECHANISM OF ACTION
ï” Dostarlimab is a humanized monoclonal antibody of the IgG4 isotype that binds to the PD-1
receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated
inhibition of the immune response, including the anti-tumor immune response.
ï” Binding of PD-1 ligands, PD-L1 and PD-L2, to PD-1 receptor found on T-cells;
inhibits T-cell proliferation and cytokine production
ï” Up-regulation of PF-1 ligands occurs in some tumors; signaling through this
pathway can contribute to inhibition of active T-cell immune surveillance of
tumors
6. USES
ï” In treatment of advanced or recurrent DNA mismatch repair
deficient/microsatellite instability-high (dMMR/MSI-H) endometrial cancer
ï” In colorectal cancer
7. SIDE EFFECTS
ï” Sepsis
ï” Acute kidney injury
ï” Urinary tract infection
ï” Abdominal pain
ï” Pyrexia
ï” Immune-mediated adverse reactions can occur including pneumonitis, colitis,
hepatitis, endocrinopathies, and nephritis
8. APPROVAL
ï” In 2020, the GARNET study announced that dostarlimab was demonstrating
potential to treat a subset of women with recurrent or advanced endometrial
cancer.
ï” In April 2021, dostarlimab was approved for the treatment of recurrent or
advanced endometrial cancer with deficient mismatch repair (dMMR), which are
genetic abnormalities that disrupt DNA repair.
ï” On 22 April 2021, the FDA granted accelerated approval to dostarlimab-gxly
(Jemperli, GlaxoSmithKline).
