JEMPERLI

Indications

• Recurrent or advanced mismatch repair deficient endometrial cancer
• Recurrent or advanced microsatellite instability-high endometrial cancer

Dosage

Adults: 500 mg by intravenous infusion every 3 weeks for the first 4 doses on weeks 1, 4, 7, and 10, followed by 1 g every 6 weeks from week 13 onwards. Adjustments may be necessary based on treatment tolerance and side effects.

Mechanism of action

Dostarlimab binds to the programmed death-1 (PD-1) receptor on T cells, preventing its interaction with PD-L1 and PD-L2 ligands. This blockade enhances T-cell activation, proliferation, and cytokine production, leading to a more robust immune response against tumor cells. By inhibiting PD-1, dostarlimab allows for increased recognition and destruction of cancer cells by the immune system.

Pharmacodynamics

Dostarlimab's pharmacodynamic effects are primarily mediated through the enhancement of T-cell responses against tumor antigens. The inhibition of PD-1 signaling results in increased effector T-cell activity, which can lead to tumor regression in patients with specific malignancies. The clinical efficacy of dostarlimab is associated with biomarkers such as microsatellite instability and mismatch repair deficiency, which are indicative of a higher likelihood of response to immunotherapy.

Pharmacokinetics

Dostarlimab exhibits linear pharmacokinetics with a half-life that allows for administration every three weeks or six weeks, depending on the treatment phase. Following intravenous administration, dostarlimab is distributed throughout the body, and its therapeutic concentration is maintained by repeated dosing. It is metabolized through proteolytic degradation, consistent with other monoclonal antibodies, and is primarily eliminated via the reticuloendothelial system.

Adverse effects

• Adrenal insufficiency
• Anaemia
• Arthralgia
• Autoimmune haemolytic anaemia
• Chills
• Diarrhoea
• Enterocolitis
• Gastrointestinal disorders
• Hyperthyroidism
• Hypertransaminasaemia
• Hypothyroidism
• Infusion-related reactions
• Myalgia
• Nausea
• Pancreatitis

Precautions

• History of severe or life-threatening cutaneous adverse reactions associated with other immunostimulant antineoplastic drugs
• Increased risk of transplant-related complications in patients receiving allogeneic haematopoietic stem cell transplant
• Increased risk of rejection in solid organ transplant recipients

Pregnancy

Avoid-limited information available.

Breast-feeding

Avoid during treatment and for at least 4 months after last treatment-no information available.

Storage

Store in a refrigerator (2–8°C) and protect from light-consult product literature for storage conditions after dilution.

Formulations

• Solution for infusion: Dostarlimab 500 mg/10 mL concentrate for solution for infusion vials