Dostarlimab

1. DRUG OF THE WEEK
M5 UNIT
UNIT CHIEF
PROFESSOR DR. VP KANNAN MD
ASSISTANT PROFESSORS:
DR.M. AMUDHAN MD
DR.SHRIRAM GANESH MD

2. DOSTARLIMAB
(JEMPERLI)

3. DOSTARLIMAB
 Dostarlimab is a programmed death receptor-1 (PD-1)–blocking monoclonal
antibody.
 Is an antineoplastic agent
 Recently approved in treatment of endometrial cancer and colorectal cancer

4. PHARMAKOKINETICS
 The mean terminal elimination half-life of dostarlimab is 25.4 days.
 Route of administration – IV
 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
 Diluted in NS or 5%D and administed as slow IV infusion over 30 mins
 Cost- 3.40 lakhs

5. MECHANISM OF ACTION
 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.
 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
 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
 In treatment of advanced or recurrent DNA mismatch repair
deficient/microsatellite instability-high (dMMR/MSI-H) endometrial cancer
 In colorectal cancer

7. SIDE EFFECTS
 Sepsis
 Acute kidney injury
 Urinary tract infection
 Abdominal pain
 Pyrexia
 Immune-mediated adverse reactions can occur including pneumonitis, colitis,
hepatitis, endocrinopathies, and nephritis

8. APPROVAL
 In 2020, the GARNET study announced that dostarlimab was demonstrating
potential to treat a subset of women with recurrent or advanced endometrial
cancer.
 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.
 On 22 April 2021, the FDA granted accelerated approval to dostarlimab-gxly
(Jemperli, GlaxoSmithKline).

9. THANK YOU