Tuesday, September 7, 2021


Merck’s KEYTRUDA® (pembrolizumab) Accredited in China in Mixture With Chemotherapy for First-Line Remedy of Sufferers With Domestically Superior Unresectable or Metastatic Esophageal or Gastroesophageal Junction (GEJ) Carcinoma

KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), often called MSD outdoors america and Canada, right now introduced that KEYTRUDA, Merck’s anti-PD-1 remedy,…

By Staff , in Platinum , at September 7, 2021


KENILWORTH, N.J.–(BUSINESS WIRE)–Merck (NYSE: MRK), often called MSD outdoors america and Canada, right now introduced that KEYTRUDA, Merck’s anti-PD-1 remedy, has been accepted by the Nationwide Medical Merchandise Administration (NMPA) in China together with platinum- and fluoropyrimidine-based chemotherapy for the first-line therapy of sufferers with regionally superior unresectable or metastatic carcinoma of the esophagus or gastroesophageal junction (GEJ). This new indication was granted approval based mostly on general survival (OS) findings from the pivotal Part 3 KEYNOTE-590 trial. KEYTRUDA is now accepted for eight indications throughout 5 several types of most cancers in China.

“In China, esophageal and gastroesophageal junction cancers are main causes of loss of life, and there have been few therapy advances for sufferers over the previous a number of a long time,” stated Dr. Scot Ebbinghaus, vp, scientific analysis, Merck Analysis Laboratories. “With this approval of KEYTRUDA plus chemotherapy – the primary for an anti-PD-1 routine within the first-line setting – we are able to now present sufferers with an immunotherapy therapy possibility earlier in the middle of therapy that has been proven to considerably enhance survival.”

Within the world KEYNOTE-590 examine, KEYTRUDA together with chemotherapy (5-fluorouracil [5-FU] plus cisplatin) demonstrated statistically vital enhancements in OS and progression-free survival (PFS) in contrast with 5-FU and cisplatin alone. KEYTRUDA plus 5-FU and cisplatin lowered the chance of loss of life by 27% (HR=0.73 [95% CI, 0.62-0.86]; p<0.0001). The median OS was 12.4 months (95% CI, 10.5-14.0) for sufferers handled with KEYTRUDA plus 5-FU and cisplatin and 9.8 months (95% CI, 8.8-10.8) for sufferers handled with 5-FU and cisplatin alone. KEYTRUDA plus 5-FU and cisplatin lowered the chance of illness development or loss of life by 35% (HR=0.65 [95% CI, 0.55-0.76]; p<0.0001). The median PFS was 6.3 months (95% CI, 6.2-6.9) for sufferers handled with KEYTRUDA plus 5-FU and cisplatin and 5.8 months (95% CI, 5.0-6.0) for sufferers handled with 5-FU and cisplatin alone in all randomized sufferers. The Chinese language bundle insert notes that the protection of KEYTRUDA plus chemotherapy was investigated in 51 Chinese language sufferers with esophageal carcinoma in KEYNOTE-590, and the protection profile of the Chinese language sufferers was usually in line with the identified security profiles of KEYTRUDA monotherapy and chemotherapy.

“In comparison with the remainder of the world, China has a disproportionate variety of sufferers who’re identified with and who die from esophageal most cancers, the fifth mostly identified most cancers and the fourth main reason for cancer-related loss of life within the nation,” stated Prof. Shen Lin, vp, Medical Oncology, Beijing Most cancers Hospital and Peking College, and deputy director, Beijing Institute for Most cancers Analysis. “This approval for KEYTRUDA supplies an essential new choice to sufferers with superior esophageal carcinoma in China who at the moment have restricted accessible therapy choices within the first-line setting.”

“We’re thrilled to carry this new KEYTRUDA mixture therapy possibility, which has proven vital enhancements in progression-free and general survival, to esophageal most cancers sufferers in China,” stated Anna Van Acker, president, MSD China. “We proceed to work with urgency to handle the unmet wants of sufferers in China by our broad world scientific program, and we’re dedicated to working with stakeholders to make sure affected person entry.”

That is the second indication for KEYTRUDA in esophageal most cancers in China. Along with this new approval, KEYTRUDA is accepted in China for a second-line therapy of sure sufferers with regionally superior or metastatic esophageal squamous cell carcinoma whose tumors specific PD-L1 (Mixed Constructive Rating [CPS] ≥10). Merck is continuous to check KEYTRUDA throughout a number of settings and levels of gastrointestinal most cancers by its broad scientific program, together with research in esophageal, gastric, hepatobiliary, pancreatic, colorectal and anal cancers.

About KEYNOTE-590

KEYNOTE-590 (ClinicalTrials.gov, NCT03189719) is a multicenter, randomized, double-blind, placebo-controlled trial that enrolled 749 sufferers with regionally superior unresectable or metastatic esophageal or GEJ carcinoma (Siewert sort I) who weren’t candidates for surgical resection or definitive chemoradiation. Sufferers had been randomized (1:1) to obtain both KEYTRUDA (200 mg on Day 1 each three weeks) or placebo (on Day 1 each three weeks) together with cisplatin (80 mg/m2 on Day 1 each three weeks for as much as six cycles) plus 5-FU (800 mg/m2 per day on Days 1 to five each three weeks, or per native customary for 5-FU administration, for as much as 24 months); all examine medicines had been administered through intravenous infusion.

The first endpoints had been OS and PFS, as assessed by the investigator based on RECIST v1.1, in squamous cell histology, PD-L1 expression (CPS ≥10) and in all sufferers. The secondary endpoints embody goal response price and period of response, as assessed by the investigator based on RECIST v1.1.

About Esophageal Most cancers in China

Esophageal most cancers begins within the interior layer (mucosa) of the esophagus and grows outward. Worldwide, esophageal most cancers is the eighth mostly identified most cancers and the sixth main reason for loss of life from most cancers worldwide. In China, esophageal most cancers is the fifth mostly identified most cancers and the fourth main reason for loss of life from most cancers. It’s estimated there have been greater than 324,000 new instances of esophageal most cancers identified and greater than 301,000 deaths from the illness in 2020.

About KEYTRUDA® (pembrolizumab) Injection, 100 mg

KEYTRUDA is an anti-programmed loss of life receptor-1 (PD-1) remedy that works by rising the flexibility of the physique’s immune system to assist detect and battle tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interplay between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which can have an effect on each tumor cells and wholesome cells.

Merck has the trade’s largest immuno-oncology scientific analysis program. There are at the moment greater than 1,500 trials finding out KEYTRUDA throughout all kinds of cancers and therapy settings. The KEYTRUDA scientific program seeks to know the position of KEYTRUDA throughout cancers and the elements which will predict a affected person’s chance of benefitting from therapy with KEYTRUDA, together with exploring a number of totally different biomarkers.

Chosen KEYTRUDA® (pembrolizumab) Indications within the U.S.

Melanoma

KEYTRUDA is indicated for the therapy of sufferers with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant therapy of sufferers with melanoma with involvement of lymph node(s) following full resection.

Non-Small Cell Lung Most cancers

KEYTRUDA, together with pemetrexed and platinum chemotherapy, is indicated for the first-line therapy of sufferers with metastatic nonsquamous non-small cell lung most cancers (NSCLC), with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, together with carboplatin and both paclitaxel or paclitaxel protein-bound, is indicated for the first-line therapy of sufferers with metastatic squamous NSCLC.

KEYTRUDA, as a single agent, is indicated for the first-line therapy of sufferers with NSCLC expressing PD-L1 [tumor proportion score (TPS) ≥1%] as decided by an FDA-approved check, with no EGFR or ALK genomic tumor aberrations, and is:

  • stage III the place sufferers aren’t candidates for surgical resection or definitive chemoradiation, or
  • metastatic.

KEYTRUDA, as a single agent, is indicated for the therapy of sufferers with metastatic NSCLC whose tumors specific PD-L1 (TPS ≥1%) as decided by an FDA-approved check, with illness development on or after platinum-containing chemotherapy. Sufferers with EGFR or ALK genomic tumor aberrations ought to have illness development on FDA-approved remedy for these aberrations previous to receiving KEYTRUDA.

Head and Neck Squamous Cell Most cancers

KEYTRUDA, together with platinum and fluorouracil (FU), is indicated for the first-line therapy of sufferers with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC).

KEYTRUDA, as a single agent, is indicated for the first-line therapy of sufferers with metastatic or with unresectable, recurrent HNSCC whose tumors specific PD-L1 [combined positive score (CPS ≥1)] as decided by an FDA-approved check.

KEYTRUDA, as a single agent, is indicated for the therapy of sufferers with recurrent or metastatic HNSCC with illness development on or after platinum-containing chemotherapy.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the therapy of grownup sufferers with relapsed or refractory classical Hodgkin lymphoma (cHL).

KEYTRUDA is indicated for the therapy of pediatric sufferers with refractory cHL, or cHL that has relapsed after 2 or extra strains of remedy.

Major Mediastinal Giant B-Cell Lymphoma

KEYTRUDA is indicated for the therapy of grownup and pediatric sufferers with refractory main mediastinal giant B-cell lymphoma (PMBCL), or who’ve relapsed after 2 or extra prior strains of remedy. KEYTRUDA shouldn’t be really useful for therapy of sufferers with PMBCL who require pressing cytoreductive remedy.

Urothelial Carcinoma

KEYTRUDA is indicated for the therapy of sufferers with regionally superior or metastatic urothelial carcinoma (mUC):

  • who aren’t eligible for any platinum-containing chemotherapy, or
  • who’ve illness development throughout or following platinum-containing chemotherapy or inside 12 months of neoadjuvant or adjuvant therapy with platinum-containing chemotherapy.

KEYTRUDA is indicated for the therapy of sufferers with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder most cancers (NMIBC) with carcinoma in situ with or with out papillary tumors who’re ineligible for or have elected to not bear cystectomy.

Microsatellite Instability-Excessive or Mismatch Restore Poor Most cancers

KEYTRUDA is indicated for the therapy of grownup and pediatric sufferers with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch restore poor (dMMR) strong tumors which have progressed following prior therapy and who haven’t any passable various therapy choices.

This indication is accepted below accelerated approval based mostly on tumor response price and sturdiness of response. Continued approval for this indication could also be contingent upon verification and outline of scientific profit within the confirmatory trials. The protection and effectiveness of KEYTRUDA in pediatric sufferers with MSI-H central nervous system cancers haven’t been established.

Microsatellite Instability-Excessive or Mismatch Restore Poor Colorectal Most cancers

KEYTRUDA is indicated for the therapy of sufferers with unresectable or metastatic MSI-H or dMMR colorectal most cancers (CRC).

Gastric Most cancers

KEYTRUDA, together with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line therapy of sufferers with regionally superior unresectable or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. This indication is accepted below accelerated approval based mostly on tumor response price and sturdiness of response. Continued approval for this indication could also be contingent upon verification and outline of scientific profit within the confirmatory trials.

Esophageal Most cancers

KEYTRUDA is indicated for the therapy of sufferers with regionally superior or metastatic esophageal or GEJ (tumors with epicenter 1 to five centimeters above the GEJ) carcinoma that isn’t amenable to surgical resection or definitive chemoradiation both:

  • together with platinum- and fluoropyrimidine-based chemotherapy, or
  • as a single agent after a number of prior strains of systemic remedy for sufferers with tumors of squamous cell histology that specific PD-L1 (CPS ≥10) as decided by an FDA-approved check.

Cervical Most cancers

KEYTRUDA is indicated for the therapy of sufferers with recurrent or metastatic cervical most cancers with illness development on or after chemotherapy whose tumors specific PD-L1 (CPS ≥1) as decided by an FDA-approved check. This indication is accepted below accelerated approval based mostly on tumor response price and sturdiness of response. Continued approval for this indication could also be contingent upon verification and outline of scientific profit within the confirmatory trials.

Hepatocellular Carcinoma

KEYTRUDA is indicated for the therapy of sufferers with hepatocellular carcinoma (HCC) who’ve been beforehand handled with sorafenib. This indication is accepted below accelerated approval based mostly on tumor response price and sturdiness of response. Continued approval for this indication could also be contingent upon verification and outline of scientific profit within the confirmatory trials.

Merkel Cell Carcinoma

KEYTRUDA is indicated for the therapy of grownup and pediatric sufferers with recurrent regionally superior or metastatic Merkel cell carcinoma (MCC). This indication is accepted below accelerated approval based mostly on tumor response price and sturdiness of response. Continued approval for this indication could also be contingent upon verification and outline of scientific profit within the confirmatory trials.

Renal Cell Carcinoma

KEYTRUDA, together with axitinib, is indicated for the first-line therapy of grownup sufferers with superior renal cell carcinoma.

Tumor Mutational Burden-Excessive Most cancers

KEYTRUDA is indicated for the therapy of grownup and pediatric sufferers with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase] strong tumors, as decided by an FDA-approved check, which have progressed following prior therapy and who haven’t any passable various therapy choices. This indication is accepted below accelerated approval based mostly on tumor response price and sturdiness of response. Continued approval for this indication could also be contingent upon verification and outline of scientific profit within the confirmatory trials. The protection and effectiveness of KEYTRUDA in pediatric sufferers with TMB-H central nervous system cancers haven’t been established.

Cutaneous Squamous Cell Carcinoma

KEYTRUDA is indicated for the therapy of sufferers with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) or regionally superior cSCC that isn’t curable by surgical procedure or radiation.

Triple-Damaging Breast Most cancers

KEYTRUDA is indicated for the therapy of sufferers with high-risk early-stage triple-negative breast most cancers (TNBC) together with chemotherapy as neoadjuvant therapy, after which continued as a single agent as adjuvant therapy after surgical procedure.

KEYTRUDA, together with chemotherapy, is indicated for the therapy of sufferers with regionally recurrent unresectable or metastatic TNBC whose tumors specific PD-L1 (CPS ≥10) as decided by an FDA-approved check.

Chosen Necessary Security Data for KEYTRUDA

Extreme and Deadly Immune-Mediated Hostile Reactions

KEYTRUDA is a monoclonal antibody that belongs to a category of medication that bind to both the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby eradicating inhibition of the immune response, probably breaking peripheral tolerance and inducing immune-mediated opposed reactions. Immune-mediated opposed reactions, which can be extreme or deadly, can happen in any organ system or tissue, can have an effect on a couple of physique system concurrently, and might happen at any time after beginning therapy or after discontinuation of therapy. Necessary immune-mediated opposed reactions listed right here might not embody all doable extreme and deadly immune-mediated opposed reactions.

Monitor sufferers carefully for signs and indicators which may be scientific manifestations of underlying immune-mediated opposed reactions. Early identification and administration are important to make sure protected use of anti–PD-1/PD-L1 remedies. Consider liver enzymes, creatinine, and thyroid operate at baseline and periodically throughout therapy. For sufferers with TNBC handled with KEYTRUDA within the neoadjuvant setting, monitor blood cortisol at baseline, previous to surgical procedure, and as clinically indicated. In instances of suspected immune-mediated opposed reactions, provoke acceptable workup to exclude various etiologies, together with an infection. Institute medical administration promptly, together with specialty session as acceptable.

Withhold or completely discontinue KEYTRUDA relying on severity of the immune-mediated opposed response. Typically, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid remedy (1 to 2 mg/kg/day prednisone or equal) till enchancment to Grade 1 or much less. Upon enchancment to Grade 1 or much less, provoke corticosteroid taper and proceed to taper over not less than 1 month. Take into account administration of different systemic immunosuppressants in sufferers whose opposed reactions aren’t managed with corticosteroid remedy.

Immune-Mediated Pneumonitis

KEYTRUDA could cause immune-mediated pneumonitis. The incidence is greater in sufferers who’ve acquired prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of sufferers receiving KEYTRUDA, together with deadly (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids had been required in 67% (63/94) of sufferers. Pneumonitis led to everlasting discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of sufferers. All sufferers who had been withheld reinitiated KEYTRUDA after symptom enchancment; of those, 23% had recurrence. Pneumonitis resolved in 59% of the 94 sufferers.

Pneumonitis occurred in 8% (31/389) of grownup sufferers with cHL receiving KEYTRUDA as a single agent, together with Grades 3-4 in 2.3% of sufferers. Sufferers acquired high-dose corticosteroids for a median period of 10 days (vary: 2 days to 53 months). Pneumonitis charges had been comparable in sufferers with and with out prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of sufferers. Of the sufferers who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had decision.

Immune-Mediated Colitis

KEYTRUDA could cause immune-mediated colitis, which can current with diarrhea. Cytomegalovirus an infection/reactivation has been reported in sufferers with corticosteroid-refractory immune-mediated colitis. In instances of corticosteroid-refractory colitis, contemplate repeating infectious workup to exclude various etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of sufferers receiving KEYTRUDA, together with Grade 4 (<0.1%), Grade 3 (1.1%), and Grade 2 (0.4%) reactions. Systemic corticosteroids had been required in 69% (33/48); extra immunosuppressant remedy was required in 4.2% of sufferers. Colitis led to everlasting discontinuation of KEYTRUDA in 0.5% (15) and withholding in 0.5% (13) of sufferers. All sufferers who had been withheld reinitiated KEYTRUDA after symptom enchancment; of those, 23% had recurrence. Colitis resolved in 85% of the 48 sufferers.

Hepatotoxicity and Immune-Mediated Hepatitis

KEYTRUDA as a Single Agent

KEYTRUDA could cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 0.7% (19/2799) of sufferers receiving KEYTRUDA, together with Grade 4 (<0.1%), Grade 3 (0.4%), and Grade 2 (0.1%) reactions. Systemic corticosteroids had been required in 68% (13/19) of sufferers; extra immunosuppressant remedy was required in 11% of sufferers. Hepatitis led to everlasting discontinuation of KEYTRUDA in 0.2% (6) and withholding in 0.3% (9) of sufferers. All sufferers who had been withheld reinitiated KEYTRUDA after symptom enchancment; of those, none had recurrence. Hepatitis resolved in 79% of the 19 sufferers.

KEYTRUDA with Axitinib

KEYTRUDA together with axitinib could cause hepatic toxicity. Monitor liver enzymes earlier than initiation of and periodically all through therapy. Take into account monitoring extra regularly as in comparison with when the medication are administered as single brokers. For elevated liver enzymes, interrupt KEYTRUDA and axitinib, and contemplate administering corticosteroids as wanted. With the mixture of KEYTRUDA and axitinib, Grades 3 and 4 elevated alanine aminotransferase (20%) and elevated aspartate aminotransferase (13%) had been seen at a better frequency in comparison with KEYTRUDA alone. Fifty-nine p.c of the sufferers with elevated ALT acquired systemic corticosteroids. In sufferers with ALT ≥3 instances higher restrict of regular (ULN) (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Among the many 92 sufferers who had been rechallenged with both KEYTRUDA (n=3) or axitinib (n=34) administered as a single agent or with each (n=55), recurrence of ALT ≥3 instances ULN was noticed in 1 affected person receiving KEYTRUDA, 16 sufferers receiving axitinib, and 24 sufferers receiving each. All sufferers with a recurrence of ALT ≥3 ULN subsequently recovered from the occasion.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

KEYTRUDA could cause main or secondary adrenal insufficiency. For Grade 2 or greater, provoke symptomatic therapy, together with hormone alternative as clinically indicated. Withhold KEYTRUDA relying on severity. Adrenal insufficiency occurred in 0.8% (22/2799) of sufferers receiving KEYTRUDA, together with Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.3%) reactions. Systemic corticosteroids had been required in 77% (17/22) of sufferers; of those, the bulk remained on systemic corticosteroids. Adrenal insufficiency led to everlasting discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.3% (8) of sufferers. All sufferers who had been withheld reinitiated KEYTRUDA after symptom enchancment.

Hypophysitis

KEYTRUDA could cause immune-mediated hypophysitis. Hypophysitis can current with acute signs related to mass impact comparable to headache, photophobia, or visible discipline defects. Hypophysitis could cause hypopituitarism. Provoke hormone alternative as indicated. Withhold or completely discontinue KEYTRUDA relying on severity. Hypophysitis occurred in 0.6% (17/2799) of sufferers receiving KEYTRUDA, together with Grade 4 (<0.1%), Grade 3 (0.3%), and Grade 2 (0.2%) reactions. Systemic corticosteroids had been required in 94% (16/17) of sufferers; of those, the bulk remained on systemic corticosteroids. Hypophysitis led to everlasting discontinuation of KEYTRUDA in 0.1% (4) and withholding in 0.3% (7) of sufferers. All sufferers who had been withheld reinitiated KEYTRUDA after symptom enchancment.

Thyroid Issues

KEYTRUDA could cause immune-mediated thyroid problems. Thyroiditis can current with or with out endocrinopathy. Hypothyroidism can observe hyperthyroidism. Provoke hormone alternative for hypothyroidism or institute medical administration of hyperthyroidism as clinically indicated. Withhold or completely discontinue KEYTRUDA relying on severity. Thyroiditis occurred in 0.6% (16/2799) of sufferers receiving KEYTRUDA, together with Grade 2 (0.3%). None discontinued, however KEYTRUDA was withheld in <0.1% (1) of sufferers.

Hyperthyroidism occurred in 3.4% (96/2799) of sufferers receiving KEYTRUDA, together with Grade 3 (0.1%) and Grade 2 (0.8%). It led to everlasting discontinuation of KEYTRUDA in <0.1% (2) and withholding in 0.3% (7) of sufferers. All sufferers who had been withheld reinitiated KEYTRUDA after symptom enchancment. Hypothyroidism occurred in 8% (237/2799) of sufferers receiving KEYTRUDA, together with Grade 3 (0.1%) and Grade 2 (6.2%). It led to everlasting discontinuation of KEYTRUDA in <0.1% (1) and withholding in 0.5% (14) of sufferers. All sufferers who had been withheld reinitiated KEYTRUDA after symptom enchancment. The vast majority of sufferers with hypothyroidism required long-term thyroid hormone alternative. The incidence of latest or worsening hypothyroidism was greater in 1185 sufferers with HNSCC, occurring in 16% of sufferers receiving KEYTRUDA as a single agent or together with platinum and FU, together with Grade 3 (0.3%) hypothyroidism. The incidence of latest or worsening hypothyroidism was greater in 389 grownup sufferers with cHL (17%) receiving KEYTRUDA as a single agent, together with Grade 1 (6.2%) and Grade 2 (10.8%) hypothyroidism.

Sort 1 Diabetes Mellitus (DM), Which Can Current With Diabetic Ketoacidosis

Monitor sufferers for hyperglycemia or different indicators and signs of diabetes. Provoke therapy with insulin as clinically indicated. Withhold KEYTRUDA relying on severity. Sort 1 DM occurred in 0.2% (6/2799) of sufferers receiving KEYTRUDA. It led to everlasting discontinuation in <0.1% (1) and withholding of KEYTRUDA in <0.1% (1) of sufferers. All sufferers who had been withheld reinitiated KEYTRUDA after symptom enchancment.

Immune-Mediated Nephritis With Renal Dysfunction

KEYTRUDA could cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.3% (9/2799) of sufferers receiving KEYTRUDA, together with Grade 4 (<0.1%), Grade 3 (0.1%), and Grade 2 (0.1%) reactions. Systemic corticosteroids had been required in 89% (8/9) of sufferers. Nephritis led to everlasting discontinuation of KEYTRUDA in 0.1% (3) and withholding in 0.1% (3) of sufferers. All sufferers who had been withheld reinitiated KEYTRUDA after symptom enchancment; of those, none had recurrence. Nephritis resolved in 56% of the 9 sufferers.

Immune-Mediated Dermatologic Hostile Reactions

KEYTRUDA could cause immune-mediated rash or dermatitis. Exfoliative dermatitis, together with Stevens-Johnson syndrome, drug rash with eosinophilia and systemic signs, and poisonous epidermal necrolysis, has occurred with anti–PD-1/PD-L1 remedies. Topical emollients and/or topical corticosteroids could also be sufficient to deal with delicate to average nonexfoliative rashes. Withhold or completely discontinue KEYTRUDA relying on severity. Immune-mediated dermatologic opposed reactions occurred in 1.4% (38/2799) of sufferers receiving KEYTRUDA, together with Grade 3 (1%) and Grade 2 (0.1%) reactions. Systemic corticosteroids had been required in 40% (15/38) of sufferers. These reactions led to everlasting discontinuation in 0.1% (2) and withholding of KEYTRUDA in 0.6% (16) of sufferers. All sufferers who had been withheld reinitiated KEYTRUDA after symptom enchancment; of those, 6% had recurrence. The reactions resolved in 79% of the 38 sufferers.

Different Immune-Mediated Hostile Reactions

The next clinically vital immune-mediated opposed reactions occurred at an incidence of <1% (until in any other case famous) in sufferers who acquired KEYTRUDA or had been reported with the usage of different anti–PD-1/PD-L1 remedies. Extreme or deadly instances have been reported for a few of these opposed reactions. Cardiac/Vascular: Myocarditis, pericarditis, vasculitis; Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (together with exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis and different ocular inflammatory toxicities can happen. Some instances might be related to retinal detachment. Numerous grades of visible impairment, together with blindness, can happen. If uveitis happens together with different immune-mediated opposed reactions, contemplate a Vogt-Koyanagi-Harada-like syndrome, as this may occasionally require therapy with systemic steroids to scale back the chance of everlasting imaginative and prescient loss; Gastrointestinal: Pancreatitis, to incorporate will increase in serum amylase and lipase ranges, gastritis, duodenitis; Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis (and related sequelae, together with renal failure), arthritis (1.5%), polymyalgia rheumatica; Endocrine: Hypoparathyroidism; Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, strong organ transplant rejection.

Infusion-Associated Reactions

KEYTRUDA could cause extreme or life-threatening infusion-related reactions, together with hypersensitivity and anaphylaxis, which have been reported in 0.2% of 2799 sufferers receiving KEYTRUDA. Monitor for indicators and signs of infusion-related reactions. Interrupt or sluggish the speed of infusion for Grade 1 or Grade 2 reactions. For Grade 3 or Grade 4 reactions, cease infusion and completely discontinue KEYTRUDA.

Issues of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Deadly and different critical problems can happen in sufferers who obtain allogeneic HSCT earlier than or after anti–PD-1/PD-L1 therapy. Transplant-related problems embody hyperacute graft-versus-host illness (GVHD), acute and persistent GVHD, hepatic veno-occlusive illness after lowered depth conditioning, and steroid-requiring febrile syndrome (with out an recognized infectious trigger). These problems might happen regardless of intervening remedy between anti–PD-1/PD-L1 therapy and allogeneic HSCT. Comply with sufferers carefully for proof of those problems and intervene promptly. Take into account the profit vs dangers of utilizing anti–PD-1/PD-L1 remedies previous to or after an allogeneic HSCT.

Elevated Mortality in Sufferers With A number of Myeloma

In trials in sufferers with a number of myeloma, the addition of KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in elevated mortality. Remedy of those sufferers with an anti–PD-1/PD-L1 therapy on this mixture shouldn’t be really useful outdoors of managed trials.

Embryofetal Toxicity

Based mostly on its mechanism of motion, KEYTRUDA could cause fetal hurt when administered to a pregnant girl. Advise ladies of this potential threat. In females of reproductive potential, confirm being pregnant standing previous to initiating KEYTRUDA and advise them to make use of efficient contraception throughout therapy and for 4 months after the final dose.

Hostile Reactions

In KEYNOTE-006, KEYTRUDA was discontinued because of opposed reactions in 9% of 555 sufferers with superior melanoma; opposed reactions resulting in everlasting discontinuation in a couple of affected person had been colitis (1.4%), autoimmune hepatitis (0.7%), allergic response (0.4%), polyneuropathy (0.4%), and cardiac failure (0.4%). The commonest opposed reactions (≥20%) with KEYTRUDA had been fatigue (28%), diarrhea (26%), rash (24%), and nausea (21%).

In KEYNOTE-054, KEYTRUDA was completely discontinued because of opposed reactions in 14% of 509 sufferers; the most typical (≥1%) had been pneumonitis (1.4%), colitis (1.2%), and diarrhea (1%). Severe opposed reactions occurred in 25% of sufferers receiving KEYTRUDA. The commonest opposed response (≥20%) with KEYTRUDA was diarrhea (28%).

In KEYNOTE-189, when KEYTRUDA was administered with pemetrexed and platinum chemotherapy in metastatic nonsquamous NSCLC, KEYTRUDA was discontinued because of opposed reactions in 20% of 405 sufferers. The commonest opposed reactions leading to everlasting discontinuation of KEYTRUDA had been pneumonitis (3%) and acute kidney damage (2%). The commonest opposed reactions (≥20%) with KEYTRUDA had been nausea (56%), fatigue (56%), constipation (35%), diarrhea (31%), decreased urge for food (28%), rash (25%), vomiting (24%), cough (21%), dyspnea (21%), and pyrexia (20%).

In KEYNOTE-407, when KEYTRUDA was administered with carboplatin and both paclitaxel or paclitaxel protein-bound in metastatic squamous NSCLC, KEYTRUDA was discontinued because of opposed reactions in 15% of 101 sufferers. Essentially the most frequent critical opposed reactions reported in not less than 2% of sufferers had been febrile neutropenia, pneumonia, and urinary tract an infection. Hostile reactions noticed in KEYNOTE-407 had been just like these noticed in KEYNOTE-189 with the exception that elevated incidences of alopecia (47% vs 36%) and peripheral neuropathy (31% vs 25%) had been noticed within the KEYTRUDA and chemotherapy arm in comparison with the placebo and chemotherapy arm in KEYNOTE-407.

In KEYNOTE-042, KEYTRUDA was discontinued because of opposed reactions in 19% of 636 sufferers with superior NSCLC; the most typical had been pneumonitis (3%), loss of life because of unknown trigger (1.6%), and pneumonia (1.4%). Essentially the most frequent critical opposed reactions reported in not less than 2% of sufferers had been pneumonia (7%), pneumonitis (3.9%), pulmonary embolism (2.4%), and pleural effusion (2.2%). The commonest opposed response (≥20%) was fatigue (25%).

In KEYNOTE-010, KEYTRUDA monotherapy was discontinued because of opposed reactions in 8% of 682 sufferers with metastatic NSCLC; the most typical was pneumonitis (1.8%). The commonest opposed reactions (≥20%) had been decreased urge for food (25%), fatigue (25%), dyspnea (23%), and nausea (20%).

In KEYNOTE-048, KEYTRUDA monotherapy was discontinued because of opposed occasions in 12% of 300 sufferers with HNSCC; the most typical opposed reactions resulting in everlasting discontinuation had been sepsis (1.7%) and pneumonia (1.3%). The commonest opposed reactions (≥20%) had been fatigue (33%), constipation (20%), and rash (20%).

In KEYNOTE-048, when KEYTRUDA was administered together with platinum (cisplatin or carboplatin) and FU chemotherapy, KEYTRUDA was discontinued because of opposed reactions in 16% of 276 sufferers with HNSCC. The commonest opposed reactions leading to everlasting discontinuation of KEYTRUDA had been pneumonia (2.5%), pneumonitis (1.8%), and septic shock (1.4%). The commonest opposed reactions (≥20%) had been nausea (51%), fatigue (49%), constipation (37%), vomiting (32%), mucosal irritation (31%), diarrhea (29%), decreased urge for food (29%), stomatitis (26%), and cough (22%).

In KEYNOTE-012, KEYTRUDA was discontinued because of opposed reactions in 17% of 192 sufferers with HNSCC. Severe opposed reactions occurred in 45% of sufferers. Essentially the most frequent critical opposed reactions reported in not less than 2% of sufferers had been pneumonia, dyspnea, confusional state, vomiting, pleural effusion, and respiratory failure. The commonest opposed reactions (≥20%) had been fatigue, decreased urge for food, and dyspnea. Hostile reactions occurring in sufferers with HNSCC had been usually just like these occurring in sufferers with melanoma or NSCLC who acquired KEYTRUDA as a monotherapy, except for elevated incidences of facial edema and new or worsening hypothyroidism.

In KEYNOTE-204, KEYTRUDA was discontinued because of opposed reactions in 14% of 148 sufferers with cHL. Severe opposed reactions occurred in 30% of sufferers receiving KEYTRUDA; these ≥1% had been pneumonitis, pneumonia, pyrexia, myocarditis, acute kidney damage, febrile neutropenia, and sepsis. Three sufferers died from causes aside from illness development: 2 from problems after allogeneic HSCT and 1 from unknown trigger. The commonest opposed reactions (≥20%) had been higher respiratory tract an infection (41%), musculoskeletal ache (32%), diarrhea (22%), and pyrexia, fatigue, rash, and cough (20% every).

In KEYNOTE-087, KEYTRUDA was discontinued because of opposed reactions in 5% of 210 sufferers with cHL. Severe opposed reactions occurred in 16% of sufferers; these ≥1% had been pneumonia, pneumonitis, pyrexia, dyspnea, GVHD, and herpes zoster. Two sufferers died from causes aside from illness development: 1 from GVHD after subsequent allogeneic HSCT and 1 from septic shock. The commonest opposed reactions (≥20%) had been fatigue (26%), pyrexia (24%), cough (24%), musculoskeletal ache (21%), diarrhea (20%), and rash (20%).

In KEYNOTE-170, KEYTRUDA was discontinued because of opposed reactions in 8% of 53 sufferers with PMBCL. Severe opposed reactions occurred in 26% of sufferers and included arrhythmia (4%), cardiac tamponade (2%), myocardial infarction (2%), pericardial effusion (2%), and pericarditis (2%). Six (11%) sufferers died inside 30 days of begin of therapy. The commonest opposed reactions (≥20%) had been musculoskeletal ache (30%), higher respiratory tract an infection and pyrexia (28% every), cough (26%), fatigue (23%), and dyspnea (21%).

In KEYNOTE-052, KEYTRUDA was discontinued because of opposed reactions in 11% of 370 sufferers with regionally superior or mUC. Severe opposed reactions occurred in 42% of sufferers; these ≥2% had been urinary tract an infection, hematuria, acute kidney damage, pneumonia, and urosepsis. The commonest opposed reactions (≥20%) had been fatigue (38%), musculoskeletal ache (24%), decreased urge for food (22%), constipation (21%), rash (21%), and diarrhea (20%).

In KEYNOTE-045, KEYTRUDA was discontinued because of opposed reactions in 8% of 266 sufferers with regionally superior or mUC. The commonest opposed response leading to everlasting discontinuation of KEYTRUDA was pneumonitis (1.9%). Severe opposed reactions occurred in 39% of KEYTRUDA-treated sufferers; these ≥2% had been urinary tract an infection, pneumonia, anemia, and pneumonitis. The commonest opposed reactions (≥20%) in sufferers who acquired KEYTRUDA had been fatigue (38%), musculoskeletal ache (32%), pruritus (23%), decreased urge for food (21%), nausea (21%), and rash (20%).

In KEYNOTE-057, KEYTRUDA was discontinued because of opposed reactions in 11% of 148 sufferers with high-risk NMIBC. The commonest opposed response leading to everlasting discontinuation of KEYTRUDA was pneumonitis (1.4%). Severe opposed reactions occurred in 28% of sufferers; these ≥2% had been pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract an infection (2%). The commonest opposed reactions (≥20%) had been fatigue (29%), diarrhea (24%), and rash (24%).

Hostile reactions occurring in sufferers with MSI-H or dMMR CRC had been just like these occurring in sufferers with melanoma or NSCLC who acquired KEYTRUDA as a monotherapy.

In KEYNOTE-811, when KEYTRUDA was administered together with trastuzumab, fluoropyrimidine- and platinum-containing chemotherapy, KEYTRUDA was discontinued because of opposed reactions in 6% of 217 sufferers with regionally superior unresectable or metastatic HER2+ gastric or GEJ adenocarcinoma. The commonest opposed response leading to everlasting discontinuation was pneumonitis (1.4%). Within the KEYTRUDA arm versus placebo, there was a distinction of ≥5% incidence between sufferers handled with KEYTRUDA versus customary of look after diarrhea (53% vs 44%) and nausea (49% vs 44%).

The commonest opposed reactions (reported in ≥20%) in sufferers receiving KEYTRUDA together with chemotherapy had been fatigue/asthenia, nausea, constipation, diarrhea, decreased urge for food, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal irritation, stomatitis, headache, weight reduction, belly ache, arthralgia, myalgia, and insomnia.

In KEYNOTE-590, when KEYTRUDA was administered with cisplatin and fluorouracil to sufferers with metastatic or regionally superior esophageal or GEJ (tumors with epicenter 1 to five centimeters above the GEJ) carcinoma who weren’t candidates for surgical resection or definitive chemoradiation, KEYTRUDA was discontinued because of opposed reactions in 15% of 370 sufferers. The commonest opposed reactions leading to everlasting discontinuation of KEYTRUDA (≥1%) had been pneumonitis (1.6%), acute kidney damage (1.1%), and pneumonia (1.1%). The commonest opposed reactions (≥20%) with KEYTRUDA together with chemotherapy had been nausea (67%), fatigue (57%), decreased urge for food (44%), constipation (40%), diarrhea (36%), vomiting (34%), stomatitis (27%), and weight reduction (24%).

Hostile reactions occurring in sufferers with esophageal most cancers who acquired KEYTRUDA as a monotherapy had been just like these occurring in sufferers with melanoma or NSCLC who acquired KEYTRUDA as a monotherapy.

In KEYNOTE-158, KEYTRUDA was discontinued because of opposed reactions in 8% of 98 sufferers with recurrent or metastatic cervical most cancers. Severe opposed reactions occurred in 39% of sufferers receiving KEYTRUDA; essentially the most frequent included anemia (7%), fistula, hemorrhage, and infections [except urinary tract infections] (4.1% every). The commonest opposed reactions (≥20%) had been fatigue (43%), musculoskeletal ache (27%), diarrhea (23%), ache and belly ache (22% every), and decreased urge for food (21%).

Hostile reactions occurring in sufferers with HCC had been usually just like these in sufferers with melanoma or NSCLC who acquired KEYTRUDA as a monotherapy, except for elevated incidences of ascites (8% Grades 3-4) and immune-mediated hepatitis (2.9%). Laboratory abnormalities (Grades 3-4) that occurred at a better incidence had been elevated AST (20%), ALT (9%), and hyperbilirubinemia (10%).

Among the many 50 sufferers with MCC enrolled in examine KEYNOTE-017, opposed reactions occurring in sufferers with MCC had been usually just like these occurring in sufferers with melanoma or NSCLC who acquired KEYTRUDA as a monotherapy. Laboratory abnormalities (Grades 3-4) that occurred at a better incidence had been elevated AST (11%) and hyperglycemia (19%).

In KEYNOTE-426, when KEYTRUDA was administered together with axitinib, deadly opposed reactions occurred in 3.3% of 429 sufferers. Severe opposed reactions occurred in 40% of sufferers, essentially the most frequent (≥1%) had been hepatotoxicity (7%), diarrhea (4.2%), acute kidney damage (2.3%), dehydration (1%), and pneumonitis (1%). Everlasting discontinuation because of an opposed response occurred in 31% of sufferers; KEYTRUDA solely (13%), axitinib solely (13%), and the mixture (8%); the most typical had been hepatotoxicity (13%), diarrhea/colitis (1.9%), acute kidney damage (1.6%), and cerebrovascular accident (1.2%). The commonest opposed reactions (≥20%) had been diarrhea (56%), fatigue/asthenia (52%), hypertension (48%), hepatotoxicity (39%), hypothyroidism (35%), decreased urge for food (30%), palmar-plantar erythrodysesthesia (28%), nausea (28%), stomatitis/mucosal irritation (27%), dysphonia (25%), rash (25%), cough (21%), and constipation (21%).

Hostile reactions occurring in sufferers with TMB-H most cancers had been just like these occurring in sufferers with different strong tumors who acquired KEYTRUDA as a single agent.

Hostile reactions occurring in sufferers with recurrent or metastatic cSCC or regionally superior cSCC had been just like these occurring in sufferers with melanoma or NSCLC who acquired KEYTRUDA as a monotherapy.

In KEYNOTE-522, when KEYTRUDA was administered with neoadjuvant chemotherapy (carboplatin and paclitaxel adopted by doxorubicin or epirubicin and cyclophosphamide) adopted by surgical procedure and continued adjuvant therapy with KEYTRUDA as a single agent (n=778) to sufferers with newly identified, beforehand untreated, high-risk early-stage TNBC, deadly opposed reactions occurred in 0.9% of sufferers, together with 1 every of adrenal disaster, autoimmune encephalitis, hepatitis, pneumonia, pneumonitis, pulmonary embolism, and sepsis in affiliation with a number of organ dysfunction syndrome and myocardial infarction. Severe opposed reactions occurred in 44% of sufferers receiving KEYTRUDA; these ≥2% had been febrile neutropenia (15%), pyrexia (3.7%), anemia (2.6%), and neutropenia (2.2%). KEYTRUDA was discontinued in 20% of sufferers because of opposed reactions. The commonest reactions (≥1%) leading to everlasting discontinuation had been elevated ALT (2.7%), elevated AST (1.5%), and rash (1%). The commonest opposed reactions (≥20%) in sufferers receiving KEYTRUDA had been fatigue (70%), nausea (67%), alopecia (61%), rash (52%), constipation (42%), diarrhea and peripheral neuropathy (41% every), stomatitis (34%), vomiting (31%), headache (30%), arthralgia (29%), pyrexia (28%), cough (26%), belly ache (24%), decreased urge for food (23%), insomnia (21%), and myalgia (20%).

In KEYNOTE-355, when KEYTRUDA and chemotherapy (paclitaxel, paclitaxel protein-bound, or gemcitabine and carboplatin) had been administered to sufferers with regionally recurrent unresectable or metastatic TNBC who had not been beforehand handled with chemotherapy within the metastatic setting (n=596), deadly opposed reactions occurred in 2.5% of sufferers, together with cardio-respiratory arrest (0.7%) and septic shock (0.3%). Severe opposed reactions occurred in 30% of sufferers receiving KEYTRUDA together with chemotherapy; the intense reactions in ≥2% had been pneumonia (2.9%), anemia (2.2%), and thrombocytopenia (2%). KEYTRUDA was discontinued in 11% of sufferers because of opposed reactions. The commonest reactions leading to everlasting discontinuation (≥1%) had been elevated ALT (2.2%), elevated AST (1.5%), and pneumonitis (1.2%). The commonest opposed reactions (≥20%) in sufferers receiving KEYTRUDA together with chemotherapy had been fatigue (48%), nausea (44%), alopecia (34%), diarrhea and constipation (28% every), vomiting and rash (26% every), cough (23%), decreased urge for food (21%), and headache (20%).

Lactation

Due to the potential for critical opposed reactions in breastfed youngsters, advise ladies to not breastfeed throughout therapy and for 4 months after the ultimate dose.

Pediatric Use

In KEYNOTE-051, 161 pediatric sufferers (62 pediatric sufferers aged 6 months to youthful than 12 years and 99 pediatric sufferers aged 12 years to 17 years) had been administered KEYTRUDA 2 mg/kg each 3 weeks. The median period of publicity was 2.1 months (vary: 1 day to 24 months).

Hostile reactions that occurred at a ≥10% greater price in pediatric sufferers when in comparison with adults had been pyrexia (33%), vomiting (30%), leukopenia (30%), higher respiratory tract an infection (29%), neutropenia (26%), headache (25%), and Grade 3 anemia (17%).

Merck’s Deal with Most cancers

Our objective is to translate breakthrough science into revolutionary oncology medicines to assist folks with most cancers worldwide. At Merck, the potential to carry new hope to folks with most cancers drives our function and supporting accessibility to our most cancers medicines is our dedication. As a part of our deal with most cancers, Merck is dedicated to exploring the potential of immuno-oncology with one of many largest improvement packages within the trade throughout greater than 30 tumor varieties. We additionally proceed to strengthen our portfolio by strategic acquisitions and are prioritizing the event of a number of promising oncology candidates with the potential to enhance the therapy of superior cancers. For extra details about our oncology scientific trials, go to www.merck.com/clinicaltrials.

About Merck

For over 130 years, Merck, often called MSD outdoors of america and Canada, has been inventing for all times, bringing ahead medicines and vaccines for lots of the world’s most difficult illnesses in pursuit of our mission to avoid wasting and enhance lives. We exhibit our dedication to sufferers and inhabitants well being by rising entry to well being care by far-reaching insurance policies, packages and partnerships. At present, Merck continues to be on the forefront of analysis to stop and deal with illnesses that threaten folks and animals – together with most cancers, infectious illnesses comparable to HIV and Ebola, and rising animal illnesses – as we aspire to be the premier research-intensive biopharmaceutical firm on the planet. For extra info, go to www.merck.com and join with us on Twitter, Fb, Instagram, YouTube and LinkedIn.

Ahead-Wanting Assertion of Merck & Co., Inc., Kenilworth, N.J., USA

This information launch of Merck & Co., Inc., Kenilworth, N.J., USA (the “firm”) consists of “forward-looking statements” throughout the which means of the protected harbor provisions of the U.S. Non-public Securities Litigation Reform Act of 1995. These statements are based mostly upon the present beliefs and expectations of the corporate’s administration and are topic to vital dangers and uncertainties. There might be no ensures with respect to pipeline merchandise that the merchandise will obtain the mandatory regulatory approvals or that they’ll show to be commercially profitable. If underlying assumptions show inaccurate or dangers or uncertainties materialize, precise outcomes might differ materially from these set forth within the forward-looking statements.

Dangers and uncertainties embody however aren’t restricted to, normal trade situations and competitors; normal financial elements, together with rate of interest and forex change price fluctuations; the influence of the worldwide outbreak of novel coronavirus illness (COVID-19); the influence of pharmaceutical trade regulation and well being care laws in america and internationally; world traits towards well being care price containment; technological advances, new merchandise and patents attained by rivals; challenges inherent in new product improvement, together with acquiring regulatory approval; the corporate’s capability to precisely predict future market situations; manufacturing difficulties or delays; monetary instability of worldwide economies and sovereign threat; dependence on the effectiveness of the corporate’s patents and different protections for revolutionary merchandise; and the publicity to litigation, together with patent litigation, and/or regulatory actions.

The corporate undertakes no obligation to publicly replace any forward-looking assertion, whether or not because of new info, future occasions or in any other case. Further elements that would trigger outcomes to vary materially from these described within the forward-looking statements might be discovered within the firm’s 2020 Annual Report on Type 10-Okay and the corporate’s different filings with the Securities and Trade Fee (SEC) accessible on the SEC’s Web website (www.sec.gov).

Please see Prescribing Data for KEYTRUDA (pembrolizumab) at

http://www.merck.com/product/usa/pi_circulars/ok/keytruda/keytruda_pi.pdf and

Medicine Information for KEYTRUDA at

http://www.merck.com/product/usa/pi_circulars/ok/keytruda/keytruda_mg.pdf.





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