Oncology Drug Reference Sheet: Dostarlimab-Gxly
More than 40% of adult patients with mismatch repair deficient (https://www.ons.org/videos/understanding-msimmr) (dMMR) recurrent or advanced endometrial cancer had an overall response receiving dostarlimab-gxly (Jemperli), and more than 90% of those lasted six months or longer during the drug’s clinical trials. Those results led the U.S. Food and Drug Administration (FDA) to grant the agent its original accelerated approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-gxly-dmmr-endometrial-cancer) in 2021 for the indication. FDA expanded the accelerated approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-dostarlimab-gxly-dmmr-advanced-solid-tumors) later that year to include all recurrent or advanced solid tumors with dMMR demonstrated through an FDA-approved diagnostic test.
Category/Class
Anti–programmed cell death-1 (PD-1) monoclonal antibody and checkpoint inhibitor
Mechanism of Action
In healthy cells, the PD-1 ligands—PD-L1 and PD-L2—bind to the PD-1 receptor on T cells to inhibit T-cell proliferation and cytokine production. This is a checkpoint to regulate the body’s immune response. Cancer cells hinder T-cell surveillance that would typically identify and eliminate tumor cells before they can grow. Anti–PD-1 monoclonal antibodies bind to the PD1 receptor, preventing its interaction with the PD-L1 and -L2 ligands, which bypasses the inhibition checkpoint (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF) and bolsters the immune system’s ability to detect and destroy cancer cells.
Indication
Adult patients with:
- Recurrent or advanced endometrial cancer with dMMR that has progressed on or following treatment with a platinum-containing regimen
- Any solid tumor with dMMR that has progressed on or following prior treatment and who have no satisfactory alternative treatment options
Dosing
For doses 1–4, give 500 mg via IV (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF) every three weeks. Three weeks after dose 4, increase dose 5 to 1,000 mg and begin giving 1,000 mg every six weeks (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF) until patients experience disease progression or unacceptable toxicity.
Administration
Give dostarlimab-gxly via IV infusion over 30 minutes. Do not administer as IV push or bolus injection. Do not co-administer other drugs through the same infusion line. See the package insert (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF) for specifications on tubing, fittings, and inline filters.
Adverse Reactions
During the drug’s clinical trial, more than 20% of patients reported (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF) experiencing fatigue and asthenia, nausea, diarrhea, anemia, and constipation. The most common grade 3 or 4 laboratory abnormalities in at least 2% of patients (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF) were decreased lymphocytes, decreased sodium, decreased leukocytes, decreased albumin, increased creatinine, increased alkaline phosphatase and increased alanine aminotransferase. Rare but significant adverse events included (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF) severe and fatal immune-mediated adverse reactions (IMARs), infusion reactions, and complications following allogeneic hematopoietic stem cell transplant.
Nursing Considerations
Before initiating treatment, review patients’ history and medical record documentation for pregnancy status (if applicable), prior solid organ or allogeneic hematopoietic stem cell transplant, autoimmune disease, or current use of high-dose steroids for treatment of other conditions.
During infusion, monitor patients for signs or symptoms of infusion reactions and be familiar with your institution’s hypersensitivity protocol or policy for management. During and after treatment discontinuation, monitor patients closely for symptoms or signs of IMARs, which commonly present as pneumonitis, colitis, hepatitis, endocrinopathies (e.g., adrenal insufficiency, hypophysitis, thyroiditis, hypo- or hyperthyroidism, type 1 diabetes mellitus), nephritis, or dermatologic presentations such as rash or dermatitis.
Evaluate relevant lab values, such as complete blood cell counts, liver enzymes, creatinine, and thyroid function tests, at baseline, routinely during treatment, and as clinically indicated (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF) following treatment discontinuation. Notify the ordering provider immediately with any findings that suggest IMARs to initiate medical management, which may require treatment interruption, high-dose steroids, or treatment discontinuation.
Patient Education
Use effective contraception to prevent pregnancy during treatment. Do not become pregnant or breastfeed during treatment or for four months (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF) following your last dose. Dostarlimab-gxly has a risk of infusion reaction (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF); report any signs or symptom during your infusion. It also has a risk for IMARs (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF) that can develop during active treatment and following discontinuation; report any signs or symptoms you experience.
Special Considerations
No studies have assessed dostarlimab-gxly’s carcinogenicity, genotoxicity, or effect on fertility. No data are available on use in pregnant patients, but dostarlimab-gxly may cause fetal harm if administered to pregnant patients because of its mechanism of action. No overall differences in safety or effectiveness (https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Jemperli/pdf/JEMPERLI-PI-MG.PDF) were observed in older adult patients, but safety and effectiveness were not established for pediatric patients.
Safe Handling
Unconjugated monoclonal antibodies are not classified as hazardous (https://www.cdc.gov/niosh/docs/2016-161/default.html). Review your institution’s hazardous drug classification and safe handling procedures to ensure appropriate compliance with your local policy.
Patient Assistance
Visit Together With GSK Oncology (https://www.togetherwithgskoncology.com/hcp-resources/jemperli/) or call 844-4GSK-ONC (844-447-5662).