Keytruda

Keytruda (pembrolizumab) is an immunotherapy medicine used to treat many types of cancer, including non-small cell lung cancer, melanoma, triple-negative breast cancer, urothelial cancer, renal cell carcinoma, head and neck squamous cell carcinoma, cervical cancer, and others. It belongs to a class of drugs called PD-1 inhibitors, also known as immune checkpoint inhibitors.

Keytruda works by blocking the PD-1 (programmed death receptor-1) pathway on T cells, a type of immune cell. Normally, certain cancer cells can attach to PD-1 receptors on T cells to prevent detection and avoid destruction. By blocking this pathway, Keytruda allows T cells to recognize and attack cancer cells more effectively. Because it works through the immune system rather than targeting cancer cells directly, it is not chemotherapy.

Keytruda is given as an intravenous (IV) infusion over approximately 30 minutes, usually every 3 or every 6 weeks, depending on the cancer type and treatment regimen. In adults, the standard doses are 200 mg every 3 weeks or 400 mg every 6 weeks. In children, the dose is weight-based (2 mg/kg, up to 200 mg) every 3 weeks.

Keytruda has FDA approval for more than 20 cancer types, spanning over 30 individual indications, making it one of the most broadly approved cancer therapies available. Many approvals are supported by the KEYNOTE clinical trial program. Keytruda first received FDA approval on September 4, 2014, for unresectable or metastatic melanoma. Multiple approvals for additional cancer types and settings followed. There is currently no generic or biosimilar for Keytruda.

Keytruda Qlex (pembrolizumab + berahyaluronidase alfa-pmph) is a related subcutaneous injection formulation that can be administered over 1 to 2 minutes in medical offices and clinics.

Keytruda is manufactured by Merck Sharp & Dohme LLC (known as MSD outside the United States and Canada).

Keytruda (pembrolizumab) is a monoclonal antibody that works by blocking the PD-1 (programmed death receptor-1) pathway to help the immune system detect and destroy cancer cells.

• PD-1 receptors are found on T cells (T-lymphocytes), a type of white blood cell that normally detects and kills abnormal or foreign cells.
• Some cancer cells carry a protein called PD-L1 (programmed death ligand-1) on their surface. PD-L1 binds to PD-1 receptors on T cells, essentially switching them off and allowing the cancer cells to evade destruction.
• Keytruda binds to the PD-1 receptor, blocking the cancer cell's ability to switch off T cells. This restores the T cell's ability to recognize and attack the cancer.
• Because this mechanism acts on the immune system broadly rather than on a specific cancer target, it can also affect normal healthy tissues, causing immune-related side effects.

Keytruda belongs to the drug class known as PD-1 inhibitors, or immune checkpoint inhibitors. It may also be described as an anti-PD-1 monoclonal antibody. A clinical response to Keytruda is typically seen within 2 to 4 months of starting treatment, though this varies by cancer type and individual.

For many indications, treatment decisions depend on whether the tumor expresses PD-L1, which is measured using a laboratory test on a biopsy sample. The relevant threshold depends on the cancer type: some indications require a PD-L1 Combined Positive Score (CPS) of 1 or higher; others require a Tumor Proportion Score (TPS) of 1% or higher. Ask your oncologist whether PD-L1 testing is needed before starting Keytruda.

Keytruda (pembrolizumab) is FDA-approved for the following cancers. Relevant KEYNOTE or other clinical trials are listed beside each cancer approval.

Non-Small Cell Lung Cancer (NSCLC)

• In combination with pemetrexed and platinum chemotherapy as first-line treatment of adults with metastatic nonsquamous NSCLC with no EGFR or ALK genomic tumor aberrations. (KEYNOTE-189)
• In combination with carboplatin and either paclitaxel or paclitaxel protein-bound as first-line treatment of adults with metastatic squamous NSCLC. (KEYNOTE-407)
• As a single agent for the first-line treatment of 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. (KEYNOTE-024, KEYNOTE-042)
• As a single agent for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%), 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 before receiving Keytruda. (KEYNOTE-010)
• In combination with platinum-containing chemotherapy as neoadjuvant treatment, then continued as a single agent as adjuvant treatment after surgery, for adults with resectable (tumors ≥4 cm or node positive) NSCLC. (KEYNOTE-671)
• As a single agent for adjuvant treatment following resection and platinum-based chemotherapy for adults with Stage IB (T2a ≥4 cm), II, or IIIA NSCLC. (KEYNOTE-091)

Melanoma

• Unresectable or metastatic melanoma. (KEYNOTE-006, KEYNOTE-002)
• As adjuvant treatment for Stage IIB, IIC, or III melanoma following complete resection in adults and pediatrics aged 12 years and older. (KEYNOTE-716, KEYNOTE-054)

Triple-Negative Breast Cancer (TNBC)

• High-risk early-stage TNBC in combination with chemotherapy as neoadjuvant treatment, then continued as a single agent as adjuvant treatment after surgery. (KEYNOTE-522)
• In combination with sacituzumab govitecan-hziy, for the first-line treatment of unresectable locallyadvanced or metastatic TNBC in adults whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-authorized test. (KEYNOTE-D19)
• In combination with chemotherapy, for locally recurrent, unresectable or metastatic TNBC in adults whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-authorized test. (KEYNOTE-355)

Urothelial Cancer (UC)

• In combination with enfortumab vedotin for adults with locally advanced or metastatic UC. (EV-302/KEYNOTE-A39)
• As a single agent for adults with locally advanced or metastatic UC who: Are not eligible for platinum-containing chemotherapy, or (KEYNOTE-052) Have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. (KEYNOTE-045)
• In combination with enfortumab vedotin as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment of adults with muscle-invasive bladder cancer (MIBC). (KEYNOTE-905/EV-303, KEYNOTE-B15)
• As a single agent for adults with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. (KEYNOTE-057)

Renal Cell Carcinoma (RCC)

• In combination with axitinib for the first-line treatment of adults with advanced RCC. (KEYNOTE-426)
• In combination with lenvatinib for the first-line treatment of adults with advanced RCC. (KEYNOTE-581/Study 307)
• As adjuvant treatment for patients with RCC at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. (KEYNOTE-564)
• In combination with belzutifan for the adjuvant treatment of adults with RCC with a clear cell component (ccRCC) at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions. (LITESPARK-022)

Head and Neck Squamous Cell Cancer (HNSCC)

• Adults with resectable locally advanced HNSCC whose tumors express PD-L1 (CPS ≥1) as a single agent as neoadjuvant treatment, continued as adjuvant treatment in combination with radiotherapy with or without cisplatin, and then as a single agent. (KEYNOTE-689)
• In combination with platinum and FU for the first-line treatment of patients with metastatic or unresectable, recurrent HNSCC. (KEYNOTE-048)
• As a single agent for the first-line treatment of patients with metastatic or unresectable, recurrent HNSCC whose tumors express PD-L1 (CPS ≥1). (KEYNOTE-048)
• As a single agent for the treatment of patients with recurrent or metastatic HNSCC with disease progression on or after platinum-containing chemotherapy. (KEYNOTE-040)

Cervical Cancer

• In combination with chemoradiotherapy to treat patients with locally advanced cervical cancer involving the lower third of the vagina, with or without extension to the pelvic sidewall, or hydronephrosis/non-functioning kidney, or spread to adjacent pelvic organs (FIGO 2014 Stage III-IVA). (KEYNOTE-A18)
• In combination with chemotherapy, with or without bevacizumab, to treat patients with persistent, recurrent, or metastatic cervical cancer whose tumors express PD-L1 (CPS ≥1). (KEYNOTE-826)
• As a single agent to treat patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy, whose tumors express PD-L1 (CPS ≥1). (KEYNOTE-158)

Endometrial Carcinoma

• In combination with carboplatin and paclitaxel, followed by Keytruda as a single agent, for adults with primary advanced or recurrent endometrial carcinoma. (KEYNOTE-868)
• In combination with lenvatinib for the treatment of adults with advanced endometrial carcinoma that is mismatch repair proficient (pMMR) or not MSI-H, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. (KEYNOTE-775/Study 309)
• As a single agent for the treatment of adults with advanced endometrial carcinoma that is MSI-H or dMMR, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. (KEYNOTE-158)

Gastric Cancer

• In combination with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 (CPS ≥1). (KEYNOTE-811)
• 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 GEJ adenocarcinoma whose tumors express PD-L1 (CPS ≥1). (KEYNOTE-859)

Esophageal Cancer

Patients with locally advanced or metastatic esophageal or gastroesophageal junction (GEJ) carcinoma (tumors with epicenter 1 to 5 centimeters above the GEJ) that is not amenable to surgical resection or definitive chemoradiation, either:

• In combination with platinum- and fluoropyrimidine-based chemotherapy for patients whose tumors express PD-L1 (CPS ≥1). (KEYNOTE-590)
• As a single agent after one or more prior lines of systemic therapy for patients with tumors of squamous cell histology that express PD-L1 (CPS ≥10). (KEYNOTE-181)

Microsatellite Instability-High (MSI-H) or Mismatch Repair-Deficient (dMMR) Colorectal Cancer (CRC)

• Patients with unresectable or metastatic MSI-H or dMMR CRC. (KEYNOTE-177)

Classical Hodgkin Lymphoma (cHL)

• Adults with relapsed or refractory cHL. (KEYNOTE-204, KEYNOTE-087)
• Pediatrics with refractory cHL, or cHL that has relapsed after 2 or more lines of therapy. (KEYNOTE-087, KEYNOTE-051)

Hepatocellular Carcinoma (HCC)

• HCC secondary to hepatitis B in patients who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen. (KEYNOTE-394).

Biliary Tract Cancer (BTC)

• In combination with gemcitabine and cisplatin to treat patients with locally advanced unresectable or metastatic BTC. (KEYNOTE-966)

Malignant Pleural Mesothelioma (MPM)

• In combination with pemetrexed and a platinum chemotherapy as first-line treatment of adults with unresectable advanced or metastatic MPM. (KEYNOTE-483)

Ovarian Cancer

• Platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinoma in adults whose tumors express PD-L1 (CPS ≥1) and who have received 1 or 2 prior systemic treatment regimens. Used in combination with paclitaxel, with or without bevacizumab. (KEYNOTE-B96).

Cutaneous Squamous Cell Carcinoma (cSCC)

• Recurrent or metastatic cSCC or locally advanced cSCC that is not curable by surgery or radiation. (KEYNOTE-629)

Merkel Cell Carcinoma (MCC)

• Adults and pediatrics with recurrent locally advanced or metastatic MCC. (KEYNOTE-017, KEYNOTE-913)

Primary Mediastinal Large B-Cell Lymphoma (PMBCL)

• Adults and pediatrics with refractory PMBCL, or who have relapsed after 2 or more prior lines of therapy. (KEYNOTE-170)

Keytruda is not recommended for patients with PMBCL who require urgent cytoreductive therapy.

Microsatellite Instability-High (MSI-H) or Mismatch Repair-Deficient (dMMR) Cancer

• Adults and pediatrics with unresectable or metastatic MSI-H or dMMR solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. (KEYNOTE-158, KEYNOTE-164, KEYNOTE-051)

Tumor Mutational Burden-High (TMB-H) Cancer

• Adults and pediatrics with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. (KEYNOTE-158). Accelerated approval designation.

It is not known if Keytruda is safe and effective in children with TMB-H central nervous system cancers.

Keytruda is administered as an intravenous infusion over 30 minutes.

• In adults, a Keytruda infusion is usually given every 3 weeks or every 6 weeks.
• In children, Keytruda is usually given every 3 weeks.

Your healthcare provider will decide how many treatments you need and how often you receive them.

If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.

You will need frequent medical tests to help your doctor determine if you are tolerating Keytruda. Do not miss any follow-up visits.

To make sure Keytruda is safe for you, tell your doctor if you have:

• An autoimmune disorder such as rheumatoid arthritis, Crohn's disease, ulcerative colitis, lupus, or psoriasis
• Received or plan to receive a stem cell transplant that uses donor stem cells
• Had an organ or tissue transplant, including a corneal transplant
• Had radiation to your chest
• A condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome
• Are pregnant or plan to become pregnant
• Are breastfeeding.

Pregnancy

Keytruda may harm an unborn baby. Your healthcare provider will give you a pregnancy test to make sure you are not pregnant. Use effective birth control while using Keytruda and for at least 4 months after your last dose. Tell your healthcare provider right away if you think you may be pregnant or if you become pregnant duringtreatment with Keytruda.

Breastfeeding

It is not known if Keytruda passes into breast milk. Do not breastfeed while using this medicine and for at least 4 months after your last dose.

Common Side Effects

The most common side effects of Keytruda when used alone are:

• Fatigue or excessive tiredness
• Pain, including pain in the stomach, muscles, bones, or joints
• Rash or itching
• Diarrhea
• Fever
• Cough
• Decreased appetite
• Shortness of breath
• Constipation
• Nausea
• Low levels of thyroid hormone.

Side effects of Keytruda when used alone that are more common in children than adults include:

• Fever rates
• Vomiting
• Headache
• Stomach area pain
• Low levels of white blood cell counts.

Common side effects when used in combination

Keytruda with certain chemotherapy or chemotherapy with radiation therapy medicines:

Feeling tired or weak, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, trouble breathing, fever, hair loss, inflammation of the nerves that may cause pain, weakness, and paralysis in the arms and legs, swelling of the lining of the mouth, nose, eyes, throat, intestines, or vagina, mouth sores, headache, weight loss, stomach-area (abdominal) pain, joint and muscle pain, trouble sleeping, blisters or rash on the palms of your hands and soles of your feet, urinary tract infection, low levels of thyroid hormone, skin irritation in the radiation area, trouble swallowing and dry mouth.

Keytruda with chemotherapy and bevacizumab:

Tingling or numbness of the arms or legs, hair loss, low red blood cell count, feeling tired or weak, nausea, low white blood cell count, diarrhea, high blood pressure, decreased platelet count, constipation, joint aches, vomiting, urinary tract infection, rash, low levels of thyroid hormone, decreased appetite, fever, mouth sores, and nosebleed.

Keytruda with axitinib:

Diarrhea, feeling tired or weak, high blood pressure, liver problems, low levels of thyroid hormone, decreased appetite, blisters or rash on the palms of your hands and soles of your feet, nausea, mouth sores or swelling of the lining of the mouth, nose, eyes, throat, intestines, or vagina, hoarseness, rash, cough, and constipation.

Keytruda with lenvatinib:

Low levels of thyroid hormone, high blood pressure, feeling tired, diarrhea, joint and muscle pain, nausea, decreased appetite, vomiting, mouth sores, weight loss, stomach-area (abdominal) pain, urinary tract infection, protein in your urine, constipation, headache, bleeding, blisters or rash on the palms of your hands and soles of your feet, hoarseness, rash, liver problems, and kidney problems.

Keytruda with enfortumab vedotin:

Rash, tingling or numbness of the arms or legs, feeling tired, itching, diarrhea, hair loss, weight loss, decreased appetite, dry eye, nausea, constipation, changes in sense of taste, and urinary tract infection.

Keytruda with belzutifan:

Decreased hemoglobin, increased alanine aminotransferase (ALT), fatigue, increased aspartate aminotransferase (AST), decreased lymphocytes, and increased alkaline phosphatase.

Serious adverse reactions occurred in patients who received Keytruda plus belzutifan, including pneumonia, hypoxia, and anemia. Discontinuation due to adverse reactions occurred in 11% of patients receiving this combination. See the prescribing information for Keytruda and belzutifan (Welireg) for complete details.

Keytruda with sacituzumab govitecan-hziy:

Common side effects of Keytruda when given with sacituzumab govitecan-hziy include: low red blood cell count, low white blood cell count, diarrhea, nausea, feeling tired or weak, hair loss, constipation, rash, vomiting, headache, and abdominal pain.

Keytruda (pembrolizumab) may cause the following serious side effects.

Immune-Mediated Side Effects

Keytruda can cause your immune system to attack normal organs and tissues in any area of your body and can cause serious side effects.

• These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time.
• These problems may happen anytime during treatment or even after your treatment has ended

Call or see your healthcare provider right away if you develop any new or worsening signs or symptoms, including:

• Lung problems, such as cough, shortness of breath, or chest pain
• Intestinal problems, such as: diarrhea (loose stools) or more frequent bowel movements than usual stools that are black, tarry, sticky, or have blood or mucus severe stomach-area (abdomen) pain or tenderness.
• Liver problems such as yellowing of your skin or the whites of your eyes dark urine (tea colored) severe nausea or vomiting bleeding or bruising more easily than normal pain on the right side of your stomach (abdomen).
• Hormone gland problems, such as headaches that will not go away or unusual headaches urinating more often than usual eye sensitivity to light hair loss feeling cold eye problems rapid heartbeat constipation increased sweating your voice gets deeper extreme tiredness dizziness or fainting weight gain or weight loss changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness feeling hungrier or thirstier than usual.
• Kidney problems, such as a decrease in the amount of urine you produce swelling of your ankles blood in your urine loss of appetite.
• Skin problems, such as rash painful sores or ulcers in your mouth or your nose, throat, or genital area itching fever or flu-like symptoms skin blistering or peeling swollen lymph nodes.
• any new or worsening signs or symptoms in other organs, which may include: chest pain, irregular heartbeat, shortness of breath, swelling of ankles confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight persistent or severe muscle pain or weakness, muscle cramps low red blood cells, and bruising. Infusion-Related Reactions These happen during or soon after the infusion stops and can sometimes be severe or life-threatening. Signs and symptoms may include: chills or shaking dizziness itching or rash feeling like passing out flushing fever shortness of breath or wheezing back pain.

Interrupt, slow the rate of infusion, or permanently discontinue Keytruda if the reaction is severe.

Rejection of a Transplanted Organ or Tissue

In those who have had an organ transplant, rejection of a transplanted organ or tissue can occur. Your healthcare provider should tell you what signs and symptoms you should report and monitor, depending on the type of organ or tissue transplant that you have had.

Complications of Allogeneic HSCT

Complications, including graft-versus-host-disease (GVHD), can occur in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death.

• These complications may happen if you underwent transplantation either before or after being treated with Keytruda. Your healthcare provider will monitor you for these complications.

Increased mortality in multiple myeloma

Keytruda is not recommended for use in multiple myeloma in combination with a thalidomide analogue (such as thalidomide, lenalidomide, or pomalidomide) plus dexamethasone, outside of controlled clinical trials. In two randomized trials, the addition of Keytruda to this regimen was associated with increased mortality. No PD-1 or PD-L1 blocking antibody is approved for multiple myeloma in this setting.

Allergic Reactions

Get emergency medical help if you have signs of an allergic reaction to Keytruda (hives, difficulty breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Pregnancy

Keytruda may cause harm to an unborn baby. Females of reproductive potential should use effective contraception.

Notes:

• Getting medical treatment right away may help keep these problems from becoming more serious.
• Your healthcare provider will check you for these problems during treatment with Keytruda. Your healthcare provider may treat you with corticosteroids or hormone replacement medicines. Your healthcare provider may also need to delay or completely stop treatment with Keytruda if you have severe side effects.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Keytruda (pembrolizumab) works by blocking the PD-1 (programmed death receptor-1) pathway to help prevent cancer cells from hiding from the immune system.

• PD-1 receptors are found on T-cells (also called T-lymphocytes), a type of white blood cell.
• Some cancer cells avoid detection by attaching to these PD-1 receptors.
• This prevents the activation of the T-cell, which normally would target and destroy cancer.
• The cancer cells can then multiply and spread.
• When Keytruda binds to the PD-1 receptor, it prevents cancer cells from linking to and inactivating T-cells, allowing T-cell reactivation and boosting the immune system's response against cancer. This affects the tumor but can also impact normal healthy cells.

Keytruda belongs to the drug class called PD-1 inhibitors, also called immune checkpoint inhibitors. It may also be called an anti-PD-1 and PD-L1 monoclonal antibody.

A response to Keytruda is usually seen within 2-4 months of starting treatment.

Adult Dose of Keytruda for Most Cancers

• 200 mg every 3 weeks or 400 mg every 6 weeks

Longer periods between doses can be more convenient for patients.

See the Keytruda Prescribing Information for specific dosages.

Child Dose of Keytruda for Pediatric-Approved Cancers

• Weight-based dosing: 2 mg/kg (up to a maximum of 200 mg) every 3 weeks.

Your healthcare provider will decide what dosage is best for your child.

See the Keytruda Prescribing Information for specific dosages.

Keytruda is an expensive medication. The approximate list price per dose is around $12,000 when given every 3 weeks or around $24,000 when given every 6 weeks. Most patients will not pay the list price due to insurance coverage or financial assistance programs.

Most private insurance plans, Medicare, and Medicaid typically cover Keytruda for FDA-approved indications. Prior authorization is usually required. Merck offers the Merck Access Program for eligible patients who are uninsured or underinsured. Contact your insurance provider or ask your oncology team about available financial assistance options.

See Keytruda Prices, Coupons, Copay Cards & Patient Assistance for more information.

Other drugs may interact with your Keytruda infusion, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all other medicines you use.

Check for Keytruda interactions here.

Active ingredient: pembrolizumabInactive ingredients: L-histidine, polysorbate 80, sucrose, and water for injection.