Berahyaluronidase alfa and Pembrolizumab

KEYTRUDA QLEX is a combination of pembrolizumab, a programmed death receptor-1 (PD-1)-blocking antibody, and berahyaluronidase alfa, an endoglycosidase, indicated: Melanoma for the treatment of adult patients with unresectable or metastatic melanoma. for the adjuvant treatment of adult and pediatric patients 12 years and older with Stage IIB, IIC, or III melanoma following complete resection.

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. Pembrolizumab is a monoclonal antibody 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. In syngeneic mouse tumor models, combination treatment of a PD-1 blocking antibody and kinase inhibitor lenvatinib decreased tumor-associated macrophages, increased activated cytotoxic T cells, and reduced tumor growth compared to either treatment alone.

KEYTRUDA QLEX has different recommended dosage and administration than intravenous pembrolizumab. KEYTRUDA QLEX is for subcutaneous use in the thigh or abdomen only. Do not administer KEYTRUDA QLEX intravenously. KEYTRUDA QLEX must be administered by a healthcare provider. The recommended dose for adults and pediatric patients 12 years and older who weigh greater than 40 kg is: Every 3-week dosing (395 mg/4,800 units): Inject 2.4 mL subcutaneously in the abdomen or thigh over 1 minute. Every 6-week dosing (790 mg/9,600 units): Inject 4.8 mL subcutaneously in the abdomen or thigh over 2 minutes. For RCC, administer KEYTRUDA QLEX as a single agent in the adjuvant setting, or in the advanced setting with either: axitinib 5 mg orally twice daily or lenvatinib 20 mg orally once daily.

KEYTRUDA QLEX is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa, hyaluronidase or to any of its excipients.

Immune-Mediated Adverse Reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated nephritis with renal dysfunction, immune-mediated dermatologic adverse reactions, and solid organ transplant rejection. Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue based on severity and type of reaction. Hypersensitivity and Administration-Related Reactions: Interrupt injection and resume upon symptom resolution, or permanently discontinue KEYTRUDA QLEX based on the severity of reaction.

The following clinically significant adverse reactions are described elsewhere in the labeling. Severe and fatal immune-mediated adverse reactions. Hypersensitivity and Administration-Related Reactions. The most common adverse reactions (≥20%) in patients treated with KEYTRUDA QLEX in combination with chemotherapy were nausea, fatigue, and musculoskeletal pain. The safety of KEYTRUDA QLEX for the approved indications is also based on the safety of intravenous pembrolizumab given as a single agent or in combination with other antitumor medicines. The most common adverse reactions (reported in ≥20% of patients) with intravenous pembrolizumab were: As a single agent: fatigue, musculoskeletal pain, rash, diarrhea, pyrexia, cough, decreased appetite, pruritus, dyspnea, constipation, pain, abdominal pain, nausea, and hypothyroidism.

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