JEMPERLI (dostarlimab-gxly) injection

JEMPERLI (dostarlimab-gxly) injection

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JEMPERLI (dostarlimab-gxly) injection

Dostarlimab-gxly is a programmed death receptor-1 (PD-1)–blocking IgG4 humanized monoclonal antibody. Dostarlimab-gxly is produced in Chinese hamster ovary cells and has a calculated molecular weight of about 144 kDa.

JEMPERLI (dostarlimab-gxly) injection is a sterile, clear to slightly opalescent, colorless to yellow solution essentially free from visible particles. It is supplied as single-dose vials.

Each vial contains 500 mg of JEMPERLI in 10 mL of solution with a pH of 6. Each mL of solution contains 50 mg of dostarlimab-gxly, citric acid monohydrate (0.48 mg), L-arginine hydrochloride (21.07 mg), polysorbate 80 (0.2 mg), sodium chloride (1.81 mg), trisodium citrate dihydrate (6.68 mg), and Water for Injection, USP.

Indications and usage

JEMPERLI is a programmed death receptor-1 (PD-1)–blocking antibody indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced:

  • endometrial cancer, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen, or
  • solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.

These indications are approved under accelerated approval based on tumor response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Mechanism of Action

Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Dostarlimab-gxly 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. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.

Dosage and administration

The recommended dosage of JEMPERLI is:

  • Dose 1 through Dose 4: 500 mg every 3 weeks
  • Subsequent dosing beginning 3 weeks after Dose 4 (Dose 5 onwards): 1,000 mg every 6 weeks

Administer JEMPERLI as an intravenous infusion over 30 minutes. Treat patients until disease progression or unacceptable toxicity

Contraindications: None

Warnings and precautions

Severe and Fatal Immune-Mediated Adverse Reactions: JEMPERLI is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance, and inducing immune-mediated adverse reactions.

Immune-Mediated Pneumonitis: JEMPERLI can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

Immune-Mediated Colitis: JEMPERLI can cause immune-mediated colitis. Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

Immune-Mediated Hepatitis: JEMPERLI can cause immune-mediated hepatitis, which can be fatal

Adrenal Insufficiency: JEMPERLI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity

Hypophysitis: JEMPERLI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity

Thyroid Disorders: JEMPERLI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity

Thyroiditis: Thyroiditis occurred in 0.4% (2/515) of patients receiving JEMPERLI; both were Grade 2. Neither event of thyroiditis resolved; there were no discontinuations of JEMPERLI due to thyroiditis

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Hypothyroidism: Hypothyroidism occurred in 7.2% (37/515) of patients receiving JEMPERLI, all of which were Grade 2. Hypothyroidism did not lead to discontinuation of JEMPERLI and resolved in 35% of the 37 patients. Systemic corticosteroids were not required for any of the 37 patients with hypothyroidism.

Hyperthyroidism: Hyperthyroidism occurred in 1.9% (10/515) of patients receiving JEMPERLI, including Grade 2 (1.7%) and Grade 3 (0.2%). Hyperthyroidism did not lead to discontinuation of JEMPERLI and resolved in 80% of the 10 patients. Systemic corticosteroids were not required for any of the 10 patients with hyperthyroidism.

Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis: JEMPERLI can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity

Immune-Mediated Nephritis with Renal Dysfunction: JEMPERLI can cause immune-mediated nephritis, which can be fatal. Nephritis occurred in 0.4% (2/515) of patients receiving JEMPERLI; both were Grade 2. Nephritis did not lead to discontinuation of JEMPERLI and resolved in both patients. Systemic corticosteroids were required in 1 of the 2 patients experiencing nephritis.

Immune-Mediated Dermatologic Adverse Reactions: JEMPERLI can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD-1/PD-L1–blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently discontinue JEMPERLI depending on severity.

Infusion-Related Reactions: Severe or life-threatening infusion-related reactions have been reported with PD-1/PD-L1– blocking antibodies. Severe infusion-related reactions (Grade 3) occurred in 0.2% (1/515) of patients receiving JEMPERLI. All patients recovered from the infusion-related reactions.

Complications of Allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1–blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause).

These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.

Embryo-Fetal Toxicity: Based on its mechanism of action, JEMPERLI can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus, resulting in fetal death. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after the last dose.

Adverse reactions

Most common adverse reactions (≥20%) in patients with dMMR solid tumors are fatigue/asthenia, anemia, diarrhea, and nausea. Most common Grade 3 or 4 laboratory abnormalities (≥2%) are decreased lymphocytes, decreased sodium, increased alkaline phosphatase, and decreased albumin

Use in specific populations

Pregnancy: Based on its mechanism of action, JEMPERLI can cause fetal harm when administered to a pregnant woman. There are no available data on the use of JEMPERLI in pregnant women.

Lactation: There is no information regarding the presence of dostarlimab-gxly in human milk or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 4 months after the last dose of JEMPERLI.

Pediatric Use: The safety and efficacy of JEMPERLI have not been established in pediatric patients.

Geriatric Use: Of the 515 patients treated with JEMPERLI, 51% were younger than 65 years, 37% were aged 65 through 75 years, and 12% were 75 years or older. No overall differences in safety or effectiveness were observed between these patients and younger patients.

Storage

Store vial refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not freeze or shake.

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