Dostarlimab is a monoclonal antibody used to treat mismatch repair deficient endometrial cancer and solid tumors. It works by strengthening the immune system to attack cancer cells. Dostarlimab has shown promise in clinical trials, with a reported 100% remission rate for recurrent or advanced rectal cancer. It is approved by the FDA to treat recurrent or advanced endometrial cancer. Research is ongoing to explore combination therapies and further understand immunotherapy resistance and effectiveness in early-stage cancers.

1. Dostarlimab: A Medical
Miracle
Presented by:
Mr. Dhwanil Kaustubh Gawand (dhwanilkg13@gmail.com,
9152991744)
Mr. Vraj Patel (vrajk116@gmail.com, 9099769020)
Mr. Md Ajmal Siddiqui (ajmalsiddiqui641@gmail.com,
9031925756)

2. ● Dostarlimab-gxly is a PD-1 monoclonal antibody used in the treatment of adult
patients with mistmatch repair deficient (dMMR), recurrent or advanced
endometrial cancer and solid tumours with a 100% effective rate. [1]
● It has also proven to be effective on the said when the cancer has spread or
cannot be removed by surgery [2].
● It is also used in the treatment of rectal cancer which is not yet tested/approved
by FDA; but is recommended by many doctors for the same. [1] [2]
● Dostarlimab-gxly is approved by the US FDA as the originator biological
product. [3]
● The drug strengths the immune system to help it attack cancer cells, but it may
also attack healthy cells and one could develop serious or fatal side effects. [2]
Introduction

3. General Study Of The Drug
● Generic Name: Dostarlimab-gxly [2] [3]
● Brand Name: JEMPERLI [2] [3]
● Class: Antineoplastic agent, Immune Checkpoint Inhibitor, Monoclonal
Antibody, PD-1 inhibitor [2] [3]
● ROA: Intravenous [2] [3]
● Dose:
1. Endometrial cancer, recurrent or advanced (etc); 500 mg IV over 30 minutes
every 3 weeks (subsequent doses are included). [2] [3]
2. Solid tumour, recurrent or advanced (etc); 500mg IV over 30 minutes every 3
weeks (subsequent doses are included). [2] [3]

4. General Study Of The Drug
● Contraindications: Specific contraindications have not been determined. [3]
● Pregnancy Specification: May cause fetal harm. [3]
● Lactation Specification: Available evidence is inconclusive or inadequate for
harm during breast feeding. [3]
● Side Effects:
1. Common:
a. Cardiovascular: Hypertension (21%). [3]
b. Gastrointestinal: Constipation (16-20%), Diarrhoea (25-40%), Nausea (22-
30%). [3]
c. Other: Fatigue (42-48%). [3]
2. Serious:
a. Myocarditis, rash (14-42%), hyperthyroidism (2.3-3.3%), colitis (1.4%), etc..
[3]

5. About The Drug
● Dostarlimab is a humanized mAb of the IgG4 isotype, produced by recombinant
DNA technology in Mammalian Chinese Hamster ovary. [1]
● It was first discovered by AnaptysBio and licensed to TESARO Inc. under a
Collaboration and Exclusive License Agreement signed in March 2014.
● Since then, dostarlimab demonstrated potential to treat a subset of women with
EC to the reported 100% remission rate in rectal cancer. [1]
● In 2020, it had shown the potential for the treatment of EC; in 2021, it was
approved for the treatment of recurrent or advanced EC with dMMR and was
granted accelerated approval by the FDA. [1]
● And finally in 2022, it reported a 100% remission rate for rectal cancer. [1]

6. Pharmacodynamics
● Dostarlimab binds PD-1 on T cells and blocks interactions with its ligands PD-L1
and PD-L2, activating immune responses. [1]
● It is an immunotherapy that aids the body's natural anti-tumour immune response
during cancer treatment. [1]
● It is given via intravenous infusion for over 30 minutes every three to six week
depending on the cycle. [1]
● There are two chains of the drug molecule, out of which the heavy chain is
involved in the interaction between PD-1 and Dostarlimab while the light chain is
predominantly responsible for steric blockage of PD-L1 binding. [1]

7. Combination Therapy
● Dostarlimab, along with other same class drugs are going through trials to be
used in combination therapies for better and faster results. [1]
● The noticable one's include dostarlimab with niraparib for the treatment of EC
(NCT03016338), head and neck cancer (NCT04313504), endometrial or ovarian
carcinosarcoma (NCT03651206) and recurrent ovarian cancer (NCT03806049).
[1]
● Other tests include the combination of dostarlimab and TSR-022 in the treatment
of localized unresectable adult primary liver cancer (NCT03680508) and
melanoma stage III or IV (NCT04139902). [1]
● Rest can be found in Table 2 of the reference [1].

8. Conclusion
● In MMR-deficient instances, Dostarlimab has demonstrated promising benefits,
and the combination of Pembrolizumab and Lenvatinib is quickly becoming the
standard of therapy for pre-treated recurrent MMR-proficient EC. [1]
● However, further research is needed to understand the primary and secondary
mechanisms of immunotherapy resistance, as well as to use ICI in the first-line
metastatic context and early-stage malignancies. [1]
● Treatments such as Dostarlimab should become widely available, as well as
access to a medical team who will help monitor patients and intervene if the
tumor comes back. [1]
● The dramatic response of Dostarlimab in patients with rectal cancer gives hope to
find a dramatic match for the remaining cancers. [1]

9. References
● [1] Bárbara Costa and Nuno Vale's Dostarlimab: A Review,
published by Biomolecules in Volume 12, Issue 8, December
2022
● [2] Cerner Multum's Dostarlimab, medically reviewed by
drugs.com, Jun 21, 2022
● [3] Dostarlimab-gxly, published by micromedex

10. Thank you
Triials and errors are the ways of us humans, to hunt the knowledge we require to satisfy our
unending hunger.
- Mr. Dhwanil Kaustubh Gawand