PEMBROLIZUMAB-SAIDAL

Pembrolizumab is a highly selective

IgG4-kappa humanized monoclonal antibody against PD-1 receptors.

It was generated by grafting the variable sequences of a very high-affinity mouse antihuman PD-1 antibody onto a human IgG4-kappa isotype containing a stabilizing S228P Fc mutation.

It contains 32 cysteine residues and the complete folded molecule includes 4 disulfide linkages as interchain bonds and 23 interchain bonds.

It was developed by

Merck & Co and first approved for the treatment of metastatic malignant melanoma by the FDA on September 4, 2014, 7 becoming the first approved therapy against PD-1.

In the time since its initial approval, pembrolizumab has been granted approval in the treatment of a wide variety of cancers. 9, 10 In September 2025, the US FDA approved a formulation of pembrolizumab that includes berahyaluronidase alfa (Keytruda QLEX) to allow for subcutaneous administration.

Pembrolizumab is indicated for the following conditions: 13, 12, 11 Melanoma for the treatment of patients with unresectable or metastatic melanoma (adult patients in the US and patients ≥12 years old in the EU) 11 for the adjuvant treatment of adult and pediatric patients 12 years of age and older with Stage IIB, IIC, or III melanoma following complete resection Non-Small Cell Lung Cancer (NSCLC) in combination with pemetrexed and platinum-based chemotherapy as a first-line treatment for patients with metastatic nonsquamous NSCLC with no EGFR or ALK mutations in combination with carboplatin and paclitaxel as a first-line treatment for patients with metastatic squamous NSCLC as a monotherapy for the first-line treatment of NSCLC expressing PD-L1 with no EGFR or ALK mutations in patients with metastatic disease or stage III disease who are not candidates for surgery or chemoradiation as a monotherapy for the treatment of NSCLC expressing PD-L1 with disease progression on or after platinum-based chemotherapy.

• this includes patients with EGFR or ALK mutations, providing they have experienced disease progression on prior FDA-approved therapy for these aberrations in combination with platinum-based chemotherapy for the treatment of patients with resectable (tumors ≥4 cm or node positive) NSCLC as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery as a monotherapy for adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage IB, II, or IIIA NSCLC Malignant Pleural Mesothelioma (MPM) in combination with pemetrexed and platinum-based chemotherapy as a first-line treatment in adult patients with unresectable advanced or metastatic MPM Head and Neck Squamous Cell Cancer (HNSCC) as a monotherapy in adult patients with resectable locally advanced HNSCC, first as neoadjuvant treatment, then continued as adjuvant treatment in combination with radiotherapy with or without cisplatin, and then again as a single agent in combination with fluorouracil and platinum-based chemotherapy as a first-line treatment for patients with metastatic or recurrent, unresectable HNSCC as a monotherapy for the first-line treatment of patients with metastatic or recurrent, unresectable HNSCC expressing PD-L1 as a monotherapy for the treatment of patients with metastatic or recurrent HNSCC with disease progression on or after platinum-based chemotherapy Classical Hodgkin Lymphoma (cHL) for the treatment of adult patients with relapsed or refractory cHL for the treatment of pediatric patients with refractory cHL, or cHL that has relapsed following ≥2 lines of therapy Primary Mediastinal Large B-cell Lymphoma (PMBCL) for the treatment of adult and pediatric patients with refractory PMBCL, or PMBCL that has relapsed following ≥2 lines of therapy Urothelial Cancer for the treatment of locally advanced or metastatic urothelial carcinoma in patients ineligible for platinum-based chemotherapy for the treatment of locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-based chemotherapy or within 12 months of adjuvant/neoadjuvant platinum-based chemotherapy for the treatment of BCG vaccine -unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ, with or without papillary tumors, who are not candidates for cystectomy for the treatment of locally advanced or metastatic urothelial carcinoma in combination with enfortumab vedotin in adult patients in combination with enfortumab vedotin, as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment of adult patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin -containing chemotherapy Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient Cancer (dMMR) as a last-line therapy for the treatment of adult and pediatric patients with unresectable or metastatic MSI-H or dMMR solid tumors that have progressed following prior treatment for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer Gastric Cancer in combination with trastuzumab, fluoropyrimidine-, and platinum-containing chemotherapy, as a first-line treatment for patients with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD -L1 (CPS ≥1) as determined by an FDA-approved test in combination with fluoropyrimidine.

• and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma Esophageal Cancer in combination with fluoropyrimidine.

• and platinum-based chemotherapy for the treatment of patients with locally advanced or metastatic esophageal or GEJ carcinoma who are not candidates for surgery or definitive chemoradiation as a monotherapy for the treatment of locally advanced or metastatic esophageal or GEJ carcinoma expressing PD-L1 in patients who are not candidates for surgery or definitive chemoradiation Cervical Cancer in combination with other chemotherapies, with or without bevacizumab, for the treatment of persistent, recurrent, or metastatic cervical cancer expressing PD-L1 as a monotherapy for the treatment of recurrent or metastatic cervical cancer expressing PD-L1 in patients who have experienced disease progression on or after previous chemotherapy in combination with chemoradiotherapy for the treatment of patients with FIGO 2014 Stage III-IVA locally advanced cervical cancer involving the lower third of the vagina, with or without extension to pelvic side wall, or hydronephrosis/non-functioning kidney, or spread to adjacent pelvic organs Hepatocellular Carcinoma (HCC) as a monotherapy for the treatment of HCC secondary to hepatitis B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen Biliary Tract Cancer (BTC) in combination with gemcitabine and cisplatin for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer Merkel Cell Carcinoma (MCC) for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic MCC Renal Cell Carcinoma (RCC) in combination with either axitinib or lenvatinib as a first-line treatment for adult patients with advanced RCC for the adjuvant treatment of patients with RCC who are at an intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions Endometrial Carcinoma in combination with carboplatin and paclitaxel, followed by pembrolizumab as a single agent, for the t reatment of adult patients with primary advanced or recurrent endometrial carcinoma in combination with lenvatinib for the treatment of patients with advanced endometrial carcinoma that is not MSI-H or dMMR who experience disease progression following prior systemic therapy and who are not candidates for surgery or radiation therapy as a monotherapy for the treatment of patients with advanced endometrial carcinoma that is MSI-H or dMMR who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation Tumor Mutational Burden-High (TMB-H) Cancer as a last-line therapy for the treatment of adult and pediatric patients with unresectable or metastatic TMB-H solid tumors that have progressed following prior treatment Cutaneous Squamous Cell Carcinoma (cSCC) for the treatment of patients with recurrent or metastatic sCC, or locally advanced sCC that is not curable with surgery or radiation therapy Triple-Negative Breast Cancer (TNBC) for the treatment of patients with high-risk early-stage TNBC, in combination with chemotherapy as a neoadjuvant treatment followed by continued use as a single adjuvant agent following surgery in combination with chemotherapy for the treatment of locally recurrent unresectable or metastatic TNBC expressing PD-L1 Ovarian Cancer in combination with paclitaxel, with or without bevacizumab, for the treatment of adult patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma whose tumors express PD-L1 (CPS ≥1) as determined by an FDA-authorized test, and who have received one or two prior systemic treatment regimens For all approved adult indications, pembrolizumab may be used for an additional 6 weeks at 400 mg weekly.

The subcutaneous formulation of pembrolizumab (Keytruda QLEX) is indicated across most solid tumor indications for the intravenous formulation.

Pembrolizumab exerts its pharmacologic effects by releasing PD-1 pathway-mediated inhibition of the immune response, which in turn improves the anti-tumor immune response.

Due to its relatively broad mechanism of action, it is useful in the treatment of a wide variety of cancers.

The exposures from

Subcutaneous administered pembrolizumab (Keytruda QLEX) are within the range of exposures from intravenous pembrolizumab doses.

Pembrolizumab can cause immune-mediated adverse reactions.

• including hepatitis, nephritis, and pneumonitis.

• in any organ system or tissue.

Careful monitoring of the patient (including laboratory evaluation of liver, kidney, and thyroid function) should occur at baseline and periodically throughout therapy to monitor for emerging immune-mediated reactions.

Intravenous administered pembrolizumab is completely bioavailable.

Steady-state is reached after approximately 16 weeks.

Following subcutaneous administration (alongside berahyaluronidase alfa, the bioavailability of pembrolizumab is approximately 61% 6 and peak concentrations are reached within approximately 4 days.

The steady-state volume of distribution of pembrolizumab is approximately 6 liters.

Pembrolizumab is catalyzed into smaller peptides and amino acids via general protein degradation.

The terminal half-life of pembrolizumab is 22 days.

is moderately lower at steady-state (195 mL/day) than after the first dose (252 mL/day), although this decrease is not clinically significant.

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There are no data regarding overdosage with pembrolizumab.

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

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

has different recommended dosage and administration than intravenous pembrolizumab.

QLEX is for subcutaneous use in the thigh or abdomen only.

Do not administer KEYTRUDA

QLEX intravenously.

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.

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.

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.

Information for dosage modifications for adverse reactions and preparation and administration instructions. 2.1 Patient Selection See information on FDA-authorized tests for intravenous pembrolizumab.

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. metastatic NSCLC. first-line treatment of metastatic or unresectable, recurrent HNSCC. previously treated recurrent locally advanced or metastatic esophageal cancer. recurrent or metastatic cervical cancer with disease progression on or after chemotherapy.

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.

TMB-H indication, select patients for treatment with KEYTRUDA QLEX as a single agent based on TMB-H status in tumor specimens.

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, confirmation of MSI-H or dMMR status is recommended by an FDA-authorized test in patients with MSI-H or dMMR solid tumors, if feasible.

If unable to perform confirmatory

MSI-H/dMMR testing, the presence of TMB ≥10 mut/Mb, as determined by an FDA-authorized test, may be used to select patients for treatment.

Patient Selection for Combination Therapy For use of KEYTRUDA QLEX as a single agent as neoadjuvant treatment, then in combination with radiotherapy (RT) with or without chemotherapy then continued as a single agent as adjuvant treatment, select patients based on presence of positive PD-L1 expression (CPS ≥1) in resectable locally advanced HNSCC.

For use of KEYTRUDA

QLEX in combination with chemotherapy, select patients based on the presence of positive PD-L1 expression (CPS ≥1) in locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma, and esophageal or gastroesophageal junction (GEJ) carcinoma.

QLEX in combination with chemotherapy, with or without bevacizumab, select patients based on the presence of positive PD-L1 expression in persistent, recurrent, or metastatic cervical cancer.

For the pMMR/not MSI-H advanced endometrial carcinoma indication, select patients for treatment with KEYTRUDA QLEX in combination with lenvatinib based on MMR or MSI status in tumor specimens.

QLEX in combination with chemotherapy, select patients based on the presence of positive PD-L1 expression in locally recurrent unresectable or metastatic TNBC.

QLEX in combination with paclitaxel, with or without bevacizumab, select patients based on the presence of positive PD-L1 expression (CPS ≥1) in platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. 2.2 Important Dosage and Administration Information KEYTRUDA QLEX has different recommended dosage and administration instructions than intravenous pembrolizumab.

To reduce the risk of medication errors, check the vial labels to ensure that the drug being prepared and administered is KEYTRUDA QLEX for subcutaneous use and not intravenous pembrolizumab.

Do not substitute KEYTRUDA

QLEX with intravenous pembrolizumab because they have different recommended dosages and routes of administration.

Patients receiving intravenous pembrolizumab can switch to subcutaneous KEYTRUDA QLEX at their next scheduled dose.

Patients receiving subcutaneous KEYTRUDA

QLEX can switch to intravenous pembrolizumab at their next scheduled dose.

QLEX as a subcutaneous injection into the thigh or abdomen, avoiding the 5 cm area around the navel.

Every 3-week dosing (395 mg/4,800 units) : inject 2.4 mL subcutaneously over 1 minute.

Treatment duration is provided in Recommended

Dosage (Table 1).

Every 6-week dosing (790 mg/9,600 units): inject 4.8 mL subcutaneously over 2 minutes.

Inject into healthy skin and never into areas where the skin is red, bruised, tender, or hard.

Ensure the injection site is at least 2.5 cm from the previous injection site.

During treatment with KEYTRUDA

QLEX, do not administer other medications for subcutaneous use at the same site as KEYTRUDA QLEX.

QLEX must be administered by a healthcare provider. 2.3 Recommended Dosage The recommended dosages of KEYTRUDA QLEX are presented in Table 1.

Every 3-week dosing (395 mg pembrolizumab and 4,800 units berahyaluronidase alfa): inject 2.4 mL subcutaneously over 1 minute.

Every 6-week dosing (790 mg pembrolizumab and 9,600 units berahyaluronidase alfa): inject 4.8 mL subcutaneously over 2 minutes.

Table 1: Recommended Dosage Indication Recommended Dosage of KEYTRUDA QLEX Duration/Timing of Treatment Monotherapy Adult patients with unresectable or metastatic melanoma 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Until disease progression or unacceptable toxicity Adjuvant treatment of adult patients with melanoma, NSCLC, or RCC 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Until disease recurrence, unacceptable toxicity, or up to 12 months Adult patients with NSCLC, HNSCC, locally advanced or metastatic Urothelial Carcinoma, MSI-H or dMMR Cancer, MSI-H or dMMR CRC, MSI-H or dMMR Endometrial Carcinoma, Esophageal Cancer, Cervical Cancer, HCC, MCC, TMB-H Cancer, or cSCC 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Until disease progression, unacceptable toxicity, or up to 24 months Adult patients with high-risk BCG.

• unresponsive NMIBC 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Until persistent or recurrent high-risk NMIBC, disease progression, unacceptable toxicity, or up to 24 months Pediatric patients The recommended dosage for melanoma, MSI-H or dMMR cancer, MCC and TMB-H cancer has not been established in pediatric patients 12 years and older who weigh 40 kg or less. (12 years and older who weigh greater than 40 kg) with MSI-H or dMMR Cancer, MCC, or TMB.

• H Cancer 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Until disease progression, unacceptable toxicity, or up to 24 months Pediatric patients (12 years and older who weigh greater than 40 kg) for adjuvant treatment of melanoma 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Until disease recurrence, unacceptable toxicity, or up to 12 months Combination Therapy Refer to the Prescribing Information for the agents administered in combination with KEYTRUDA QLEX for recommended dosing information, as appropriate.

Adult patients with resectable

NSCLC 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Administer KEYTRUDA QLEX prior to chemotherapy when given on the same day. Neoadjuvant treatment in combination with chemotherapy for 12 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA QLEX as a single agent after surgery for 39 weeks or until disease recurrence or unacceptable toxicity Adult patients with NSCLC, MPM, HNSCC, HER2-negative Gastric Cancer, Esophageal Cancer, or BTC 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Administer KEYTRUDA QLEX prior to chemotherapy when given on the same day. Until disease progression, unacceptable toxicity, or up to 24 months Adult patients with locally advanced or metastatic urothelial cancer 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Administer KEYTRUDA QLEX after enfortumab vedotin when given on the same day. Until disease progression, unacceptable toxicity, or up to 24 months Adult patients with locally advanced HNSCC 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Administer KEYTRUDA QLEX prior to cisplatin when given on the same day. Neoadjuvant: Administer KEYTRUDA QLEX for 6 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity.

Administer KEYTRUDA QLEX in combination with RT with or without cisplatin.

QLEX as a single agent.

QLEX until disease recurrence or unacceptable toxicity or up to one year Adult patients with MIBC 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Administer KEYTRUDA QLEX after enfortumab vedotin when given on the same day. Neoadjuvant: Administer KEYTRUDA QLEX 395 mg/4,800 units every 3 weeks for 3 doses in combination with enfortumab vedotin or until disease progression that precludes curative-intent cystectomy or unacceptable toxicity.

Administer KEYTRUDA QLEX 395 mg/4,800 units every 3 weeks for 14 doses or 790 mg/9,600 units every 6 weeks for 7 doses in combination with enfortumab vedotin or until disease recurrence or unacceptable toxicity Adult patients with HER2-positive Gastric Cancer 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Administer KEYTRUDA QLEX prior to trastuzumab and chemotherapy when given on the same day. Until disease progression, unacceptable toxicity, or up to 24 months Adult patients with Cervical Cancer 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Administer KEYTRUDA QLEX prior to chemoradiotherapy or prior to chemotherapy with or without bevacizumab when given on the same day. Until disease progression, unacceptable toxicity, or for KEYTRUDA QLEX, up to 24 months Adult patients with RCC 395 mg/4,800 units every 3 weeks or 790 mg/9,600 units every 6 weeks Administer KEYTRUDA QLEX in combination with axitinib 5 mg orally twice daily When axitinib is used in combination with KEYTRUDA QLEX, dose escalation.

(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.

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.

Based on its mechanism of action, 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.

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 to 4% and to 20%, respectively.

QLEX for subcutaneous injection contains pembrolizumab and berahyaluronidase alfa.

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 alfa

In an embryo-fetal development study, pregnant rabbits were administered daily subcutaneous injections of 138,600, 403,200, or 1,209,600 U/kg berahyaluronidase alfa during the period of organogenesis (gestation days to 19).

Berahyaluronidase alfa caused delayed fetal development at doses ≥403,200 U/kg, which is >2,500 times higher than the human dose (U/kg basis).

Increased post-implantation loss and visceral malformations (supernumerary fissure lung lobe) were observed at 1,209,600 U/kg, which is >7,500 times higher than the human dose.

In an embryo-fetal development study in rats, there were no adverse embryo-fetal findings in pregnant animals administered daily subcutaneous injections of berahyaluronidase alfa at doses up to 2,520,000 U/kg (>15,000 times higher than the human dose) during the period of organogenesis (gestation days to 17).

In a pre.

• and post-natal development study in rats, pregnant animals were administered daily subcutaneous injections of 280,000, 840,000, or 2,520,000 U/kg berahyaluronidase alfa from implantation through lactation and weaning (gestation day to lactation day 21).

There were no adverse effects on sexual maturation, learning and memory, or fertility of the offspring at doses up to 2,520,000 U/kg, which is >15,000 times higher than the human dose.

The safety and effectiveness of KEYTRUDA

QLEX for the treatment of pediatric patients 12 years and older who weigh greater than 40 kg have been established for: Stage IIB, IIC, or III melanoma following complete resection Unresectable or metastatic microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) solid tumors Recurrent locally advanced or metastatic Merkel cell carcinoma Unresectable or metastatic tumor mutational burden high solid tumors (TMB-H) Use of KEYTRUDA QLEX in pediatric patients for these indications is supported by evidence from adequate and well-controlled studies of intravenous pembrolizumab in adults and additional pharmacokinetic and safety data for intravenous pembrolizumab in pediatric patients 12 years and older.

Pembrolizumab exposures in pediatric patients 12 years and older who weigh greater than 40 kg are predicted to be within range of those observed in adults at the same dosage.

QLEX have not been established in pediatric patients younger than 12 years of age for the treatment of melanoma, MCC, MSI-H or dMMR cancer, and TMB-H cancer.

QLEX have not been established in pediatric patients for other approved indications.

Intravenous pembrolizumab In

KEYNOTE-051, 173 pediatric patients (including 108 pediatric patients aged to 17 years) with advanced melanoma, lymphoma, or PD-L1 positive or MSI-H solid tumors received intravenous pembrolizumab 2 mg/kg every 3 weeks.

The median duration of exposure was 2.1 months (range: 1 day to 25 months).

Adverse reactions that occurred at a ≥10% higher rate in pediatric patients when compared to adults included pyrexia (33%), vomiting (29%), headache (25%), abdominal pain (23%), decreased lymphocyte count (13%), and decreased white blood cell count (11%).

Laboratory abnormalities that occurred at a ≥10% higher rate in pediatric patients when compared to adults were leukopenia (30%), neutropenia (28%), thrombocytopenia (22%), and Grade 3 anemia (17%).

Of the 251 patients treated with KEYTRUDA QLEX in combination with platinum doublet chemotherapy in Study MK-3745A-D77, 53% were 65 years and older and 16% were 75 years and older.

No overall differences in safety or effectiveness of KEYTRUDA QLEX have been observed between patients aged 65 years or older and younger adult patients.

The safety of KEYTRUDA

QLEX as monotherapy or in combination with other antineoplastic drugs for its approved indications has been established in adequate and well-controlled studies of intravenous pembrolizumab as a single agent and in combination with other antineoplastic drugs.

Below is a description of geriatric use information from the intravenous pembrolizumab studies.

Of 3781 patients with melanoma, NSCLC, HNSCC, or urothelial carcinoma who were treated with intravenous pembrolizumab in clinical studies, 48% were 65 years and over and 17% were 75 years and over.

Of 506 adult patients with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC following complete resection and platinum-based chemotherapy who were treated with intravenous pembrolizumab in KEYNOTE-091, 242 (48%) were 65 years and over.

Of 596 adult patients with TNBC who were treated with intravenous pembrolizumab in combination with paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin in KEYNOTE-355, 137 (23%) were 65 years and over.

Of 406 adult patients with endometrial carcinoma who were treated with intravenous pembrolizumab in combination with lenvatinib in KEYNOTE-775, 201 (50%) were 65 years and over.

Of the 564 patients with locally advanced or metastatic urothelial cancer treated with intravenous pembrolizumab in combination with enfortumab vedotin, 44% (n=247) were 65-74 years and 26% (n=144) were 75 years or older.

No overall differences in effectiveness were observed between patients 65 years of age or older and younger patients.

Patients 75 years of age or older treated with intravenous pembrolizumab in combination with enfortumab vedotin experienced a higher incidence of fatal adverse reactions than younger patients.

The incidence of fatal adverse reactions was 4% in patients younger than and 7% in patients 75 years or older.

Of the 167 patients with MIBC treated with intravenous pembrolizumab in combination with enfortumab vedotin, 37% (n=61) were 65-74 years and 46% (n=77) were 75 years or older.

The incidence of fatal adverse reactions was 4% in patients younger than and 12% in patients 75 years or older.

Of the 432 patients randomized to intravenous pembrolizumab in combination with axitinib in the KEYNOTE-426 trial, 40% were 65 years or older.

Of 294 adult patients with FIGO 2014 Stage III-IVA cervical cancer who were treated with intravenous pembrolizumab in combination with CRT in KEYNOTE-A18, 42 (14%) were 65 years and over.

Of 643 adult patients with ovarian cancer who were treated with intravenous pembrolizumab in combination with paclitaxel with or without bevacizumab in KEYNOTE-B96, 236 (37%) were 65 years and over and 58 (9%) were 75 years and over.

No overall differences in safety or effectiveness were observed between intravenous pembrolizumab-treated patients aged 65 years or older and younger adult patients.