Pembrolizumab

FDA Drug Information • Also known as: Keytruda

Brand Names: Keytruda
Dosage Form: INJECTION, SOLUTION
Product Type: DRUG FOR FURTHER PROCESSING

Description

11 DESCRIPTION KEYTRUDA QLEX is a fixed-combination drug product containing pembrolizumab and berahyaluronidase alfa. Pembrolizumab is a programmed death receptor-1 (PD 1)-blocking antibody. Pembrolizumab is a humanized monoclonal IgG4 kappa antibody with an approximate molecular weight of 149 kDa. Pembrolizumab is produced in recombinant Chinese hamster ovary (CHO) cells. Berahyaluronidase alfa is an endoglycosidase used to enhance dispersion and permeation, which facilitates delivery of increased volume of pembrolizumab that is co-administered subcutaneously. It is produced by mammalian CHO (Chinese Hamster Ovary) cells containing a DNA plasmid encoding a variant of human hyaluronidase PH20. It is a glycosylated protein with an approximate molecular weight of 49 kDa under nonreducing, deglycosylated conditions. KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution supplied in single-dose vials for subcutaneous administration. KEYTRUDA QLEX is supplied as two different configurations: Each KEYTRUDA QLEX 2.4 mL single-dose vial contains 395 mg of pembrolizumab and 4,800 units of berahyaluronidase alfa, and histidine (0.7 mg), histidine hydrochloride monohydrate (4.1 mg), methionine (3.6 mg), polysorbate 80 (0.5 mg), sucrose (168 mg), and Water for Injection, USP. The pH is 5.3-5.9. Each KEYTRUDA QLEX 4.8 mL single-dose vial contains 790 mg of pembrolizumab and 9,600 units of berahyaluronidase alfa, and histidine (1.4 mg), histidine hydrochloride monohydrate (8.2 mg), methionine (7.2 mg), polysorbate 80 (1 mg), sucrose (336 mg), and Water for Injection, USP. The pH is 5.3-5.9.

What Is Pembrolizumab Used For?

1 INDICATIONS AND USAGE 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. ( 1.1 ) for the adjuvant treatment of adult and pediatric patients 12 years and older with Stage IIB, IIC, or III melanoma following complete resection. ( 1.1 ) Non-Small Cell Lung Cancer (NSCLC) in combination with pemetrexed and platinum chemotherapy, as first-line treatment of adult patients with metastatic nonsquamous NSCLC, with no EGFR or ALK genomic tumor aberrations. ( 1.2 ) in combination with carboplatin and either paclitaxel or paclitaxel protein-bound, as first-line treatment of adult patients with metastatic squamous NSCLC. ( 1.2 ) as a single agent for the first-line treatment of adult patients with NSCLC expressing PD-L1 [Tumor Proportion Score (TPS) ≥1%] as determined by an FDA-authorized test, with no EGFR or ALK genomic tumor aberrations, and is: Stage III where patients are not candidates for surgical resection or definitive chemoradiation, or metastatic. ( 1.2 , 2.1 ) as a single agent for the treatment of adult patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-authorized test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA QLEX. ( 1.2 , 2.1 ) for the treatment of adult patients with resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum-containing chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery. ( 1.2 ) as a single agent, for adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC. ( 1.2 ) Malignant Pleural Mesothelioma (MPM) in combination with pemetrexed and platinum chemotherapy, as first-line treatment of adult patients with unresectable advanced or metastatic MPM. ( 1.3 ) Head and Neck Squamous Cell Cancer (HNSCC) for the treatment of adult patients with resectable locally advanced HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-authorized test, as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy (RT) with or without cisplatin and then as a single agent. ( 1.4 ) in combination with platinum and FU for the first-line treatment of adult patients with metastatic or with unresectable, recurrent HNSCC. ( 1.4 ) as a single agent for the first-line treatment of adult patients with metastatic or with unresectable, recurrent HNSCC whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-authorized test. ( 1.4 , 2.1 ) as a single agent for the...

Dosage and Administration

2 DOSAGE AND ADMINISTRATION KEYTRUDA QLEX has different recommended dosage and administration than intravenous pembrolizumab. ( 2.2 ) KEYTRUDA QLEX is for subcutaneous use in the thigh or abdomen only. ( 2.2 ) Do not administer KEYTRUDA QLEX intravenously. ( 2.2 ) KEYTRUDA QLEX must be administered by a healthcare provider. ( 2.2 ) 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. ( 2.3 ) Every 6-week dosing (790 mg/9,600 units): Inject 4.8 mL subcutaneously in the abdomen or thigh over 2 minutes. ( 2.3 ) 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. ( 2.3 ) For Endometrial Carcinoma, administer KEYTRUDA QLEX: in combination with carboplatin and paclitaxel regardless of MMR or MSI status, or in combination with lenvatinib 20 mg orally once daily for pMMR or not MSI-H tumors, or as a single agent for MSI-H or dMMR tumors. ( 2.3 ) See Full Prescribing Information for dosage modifications for adverse reactions and preparation and administration instructions. ( 2.4 , 2.5 ) 2.1 Patient Selection See information on FDA-authorized tests for intravenous pembrolizumab. Information on FDA-authorized tests for patient selection is available at: http://www.fda.gov/CompanionDiagnostics . Patient Selection for Single-Agent Treatment Select patients for treatment with KEYTRUDA QLEX as a single agent based on the presence of positive PD-L1 expression in: Stage III NSCLC who are not candidates for surgical resection or definitive chemoradiation [see Clinical Studies (14.3) ] . metastatic NSCLC [see Clinical Studies (14.3) ]. first-line treatment of metastatic or unresectable, recurrent HNSCC [see Clinical Studies (14.5) ] . previously treated recurrent locally advanced or metastatic esophageal cancer [see Clinical Studies (14.10) ] . recurrent or metastatic cervical cancer with disease progression on or after chemotherapy [see Clinical Studies (14.11) ] . For the MSI-H/dMMR indications, select patients for treatment with KEYTRUDA QLEX as a single agent based on MSI-H/dMMR status in tumor specimens [see Clinical Studies (14.7 , 14.8) ]. For the TMB-H indication, select patients for treatment with KEYTRUDA QLEX as a single agent based on TMB-H status in tumor specimens [see Clinical Studies (14.17) ]. Because subclonal dMMR mutations and microsatellite instability may arise in high-grade gliomas during temozolomide therapy, it is recommended to test for TMB-H, MSI-H, and dMMR in the primary tumor specimens obtained prior to initiation of temozolomide chemotherapy in patients with high-grade gliomas. Additional Patient Selection Information for MSI-H or dMMR in Patients with non-CRC Solid Tumors Due to discordance between local tests and FDA-authorized tests,...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling. Severe and fatal immune-mediated adverse reactions [see Warnings and Precautions (5.1) ] . Hypersensitivity and Administration-Related Reactions [see Warnings and Precautions (5.2) ]. The most common adverse reactions (≥20%) in patients treated with KEYTRUDA QLEX in combination with chemotherapy were nausea, fatigue, and musculoskeletal pain. ( 6.1 ) 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. ( 6.1 ) In combination with chemotherapy or chemoradiotherapy: fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, insomnia, palmar-plantar erythrodysesthesia, urinary tract infection, hypothyroidism, radiation skin injury, dysphagia, dry mouth and musculoskeletal pain. ( 6.1 ) In combination with chemotherapy and bevacizumab: peripheral neuropathy, alopecia, anemia, fatigue/asthenia, nausea, neutropenia, diarrhea, hypertension, thrombocytopenia, constipation, arthralgia, vomiting, urinary tract infection, rash, leukopenia, hypothyroidism, decreased appetite, pyrexia, epistaxis, decreased white blood cell count, and stomatitis. ( 6.1 ) In combination with axitinib: diarrhea, fatigue/asthenia, hypertension, hepatotoxicity, hypothyroidism, decreased appetite, palmar-plantar erythrodysesthesia, nausea, stomatitis/mucosal inflammation, dysphonia, rash, cough, and constipation. ( 6.1 ) In combination with lenvatinib: hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight loss, abdominal pain, urinary tract infection, proteinuria, constipation, headache, hemorrhagic events, palmar-plantar erythrodysesthesia, dysphonia, rash, hepatotoxicity, and acute kidney injury. ( 6.1 ) In combination with enfortumab vedotin: rash, peripheral neuropathy, fatigue, pruritus, diarrhea, alopecia, weight loss, decreased appetite, dry eye, nausea, constipation, dysgeusia, and urinary tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme LLC at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described in the WARNINGS AND PRECAUTIONS reflect exposure to intravenous pembrolizumab as a single agent in 2799 patients in three randomized, open-label, active-controlled trials (KEYNOTE-002, KEYNOTE-006, and KEYNOTE-010), which enrolled 912 patients with melanoma and 682 patients with NSCLC, and one single-arm trial (KEYNOTE-001), which enrolled 655 patients with melanoma and 550 patients with NSCLC. In addition to the 2799 patients, certain subsections in the WARNINGS AND PRECAUTIONS describe adverse reactions observed with exposure to KEYTRUDA QLEX in combination with platinum doublet chemotherapy in a randomized, open-label, active-controlled trial (Study MK-3475A-D77), which enrolled 251 patients with NSCLC; intravenous pembrolizumab as a single agent in a randomized, placebo-controlled trial (KEYNOTE-091), which enrolled 580 patients with resected NSCLC; a non-randomized, open-label, multi-cohort trial (KEYNOTE-012), a...

Contraindications

4 CONTRAINDICATIONS KEYTRUDA QLEX is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa, hyaluronidase or to any of its excipients. KEYTRUDA QLEX is contraindicated in patients with known hypersensitivity to berahyaluronidase alfa, hyaluronidase or to any of its excipients. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology (12.1) ] , KEYTRUDA QLEX can cause fetal harm when administered to a pregnant woman. There are no available human data informing the risk of embryo-fetal toxicity. In animal models, the PD-1/PD-L1 signaling pathway is important in the maintenance of pregnancy through induction of maternal immune tolerance to fetal tissue (see Data ) . Human IgG4 (immunoglobulins) are known to cross the placenta; therefore, pembrolizumab has the potential to be transmitted from the mother to the developing fetus. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data KEYTRUDA QLEX for subcutaneous injection contains pembrolizumab and berahyaluronidase alfa [see Description (11) ] . Pembrolizumab: Animal reproduction studies have not been conducted with pembrolizumab to evaluate its effect on reproduction and fetal development. A literature-based assessment of the effects of the PD-1 pathway on reproduction demonstrated that a central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. Blockade of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering pembrolizumab during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 knockout mice. Based on its mechanism of action, fetal exposure to pembrolizumab may increase the risk of developing immune-mediated disorders or of altering the normal immune response. Berahyaluronidase...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING KEYTRUDA QLEX (pembrolizumab and berahyaluronidase alfa-pmph) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution supplied in single-dose vials for subcutaneous administration. Each carton contains one single-dose vial either as: 395 mg pembrolizumab and 4,800 units berahyaluronidase alfa per 2.4 mL (165 mg/ 2,000 units per mL), NDC 0006-3083-01 790 mg pembrolizumab and 9,600 units berahyaluronidase alfa per 4.8 mL (165 mg/ 2,000 units per mL), NDC 0006-5083-01 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.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.