ECOG performance status 3) considered not eligible for chemotherapy. endobj Otherwise treatment should be discontinued (see sections 4.2 and 4.8). KEYTRUDA is a humanised monoclonal antibody which binds to the programmed cell death-1 (PD-1) receptor and blocks its interaction with ligands PD-L1 and PD-L2. Table 13: Efficacy results (PD-L1 TPS 50%) in KEYNOTE-042, Figure 10: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-042 (patients with PD-L1 expression TPS 50%, intent to treat population). /MediaBox [0 0 595 842] The baseline characteristics of these 129 patients included: median age 62 years (40% age 65 or older); 81% male; 78% White, 11% Asian, and 2% Black; 23% and 77% with an ECOG performance status 0 or 1, respectively; and 19% with HPV positive tumours. /PageLabels 4 0 R You have rejected additional cookies. Report a side effect with a medicine or medical device. Administration of Nuvaxovid in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus. Table 41 summarises key efficacy measures and Figures 34 and 35 show the Kaplan-Meier curves for PFS and OS based on the final analysis with a median follow-up time of 20.2 months (range: 0.3 to 53.1 months) for patients with tumour PD-L1 expression CPS 10. Patients received pembrolizumab 200 mg every 3 weeks (n=210; KEYNOTE-087) or 10 mg/kg bw every 2 weeks (n=31; KEYNOTE-013) until unacceptable toxicity or documented disease progression. Tickets cost 17 - 25 and the journey . Nominal p-Value based on log-rank test stratified by chemotherapy on study (taxane vs. gemcitabine and carboplatin) and prior treatment with same class of chemotherapy in the neoadjuvant setting (yes vs. no). |:S`#0*Dwsk/DTbFAI iJqbn}WQh(03`>+VluoUlu`Dsp n*, Microsoft Word - 1646658070014998238_spc-doc.doc. You can change your cookie settings at any time. >> The efficacy of pembrolizumab was evaluated in KEYNOTE-054, a multicentre, randomised, double-blind, placebo-controlled study in patients with completely resected stage IIIA (> 1 mm lymph node metastasis), IIIB or IIIC melanoma. Caution should be used when considering the use of pembrolizumab in a patient who has previously experienced a severe or life-threatening skin adverse reaction on prior treatment with other immune-stimulatory anti-cancer agents. This page includes guidance for pharmaceutical companies and regulators on how to prepare and review summaries of product characteristics (SmPCs) for human medicines. Chemical and physical in-use stability has been demonstrated for 6 hours at 2C to 25C from the time of first needle puncture to administration. Corticosteroids to treat adrenal insufficiency and other hormone replacement should be administered as clinically indicated. The study demonstrated statistically significant improvements in PFS, OS, and ORR in patients randomised to pembrolizumab in combination with lenvatinib compared with sunitinib. The effect of renal impairment on the clearance of pembrolizumab was evaluated by population pharmacokinetic analyses in patients with mild or moderate renal impairment compared to patients with normal renal function. When used in combination with lenvatinib, one or both medicines should be interrupted as appropriate. Insulin should be administered for type 1 diabetes, and pembrolizumab should be withheld in cases of type 1 diabetes associated with Grade 3 hyperglycaemia or ketoacidosis until metabolic control is achieved (see section 4.2). News stories, speeches, letters and notices, Reports, analysis and official statistics, Data, Freedom of Information releases and corporate reports, Information for healthcare professionals and the public on Moderna's bivalent vaccines. These conditions can develop within just a few days after vaccination and have primarily occurred within 14 days. See MHRA Guidance Mar 2018: Valproate use by women and girls and MHRA Valproate Pregnancy Prevention Programme toolkit for full details. Immune-related adverse reactions (see section 4.4). Mild COVID-19 was defined as fever, new onset cough or at least 2 or more additional COVD-19 symptoms. The study demonstrated a statistically significant improvement in PFS at its pre-specified interim analysis (HR 0.65; 95% CI 0.49, 0.86; p-Value 0.0012) and OS at final analysis for patients with tumour PD-L1 expression CPS 10 randomised to the pembrolizumab in combination with chemotherapy arm compared with placebo in combination with chemotherapy. Based on Kaplan-Meier estimates; includes 43 patients with responses of 6 months or longer, Table 43 summarises key efficacy measures for patients whose tumours expressed PD-L1 with a CPS 1 in KEYNOTE-826 from the pre-specified interim analysis. In some patients, dizziness and fatigue have been reported following administration of pembrolizumab (see section 4.8). An analysis was performed in KEYNOTE-048 in patients whose tumours expressed PD-L1 CPS 20 [pembrolizumab plus chemotherapy: n=126 (49%) vs. standard treatment: n=110 (43%) and pembrolizumab monotherapy: n=133 (52%) vs. standard treatment: n=122 (48%)] (see Table 28). Patients who experienced GVHD after their transplant procedure may be at an increased risk for GVHD after treatment with pembrolizumab. To view this licence, visit nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@nationalarchives.gov.uk. Preparation and administration of the infusion. The MHRA-GMDP database contains the following information issued by the MHRA relating to manufacturing and wholesale authorisations and certificates. OS results at interim analysis did not meet the pre-specified efficacy boundary of 0.00085861 for statistical significance. In KEYNOTE-361, a higher number of deaths within 6 months of treatment initiation followed by a long-term survival benefit was observed with pembrolizumab monotherapy compared to chemotherapy (see section 5.1). Kaplan-Meier curves for OS and PFS based on the final analysis are shown in Figures 1 and 2. The two vaccine components elicit B- and T-cell immune responses to the S protein, including neutralising antibodies, which may contribute to protection against COVID-19. Assessment of tumour status was performed at baseline and then every 8 weeks. Prior therapy included platinum-doublet regimen (100%); patients received one (69%) or two or more (29%) treatment lines. Severe skin reactions led to discontinuation of pembrolizumab in 18 (0.2%) patients. /Contents 15 0 R endobj KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic non-small cell lung carcinoma in adults whose tumours express PD-L1 with a 1% TPS and who have received at least one prior chemotherapy regimen. Table 14 summarises key efficacy measures and Figures 11 and 12 show the Kaplan-Meier curves for OS and PFS based on the final analysis with a median follow-up of 18.8 months. Among the 27 patients with small intestinal cancer, the baseline characteristics were: median age 58 years (range: 21 to 77); 33% age 65 or older; 63% male, 81% White, 11% Asian; and ECOG PS 0 (56%) and 1 (44%). Twelve percent of patients had BRAF mutations and 36% had RAS mutations; 39% and 34% were undetermined for BRAF and RAS mutations, respectively. We use some essential cookies to make this website work. In the ITT population, the median follow-up time for 151 patients treated with pembrolizumab was 24.9 months (range: 1.8 to 42.0 months). KEYNOTE-361 is a Phase III, randomised, controlled, open-label clinical study of pembrolizumab with or without platinum-based combination chemotherapy (i.e. Based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by chemotherapy on study (taxane vs. gemcitabine and carboplatin) and prior treatment with same class of chemotherapy in the neoadjuvant setting (yes vs. no). Of the 161 patients, 137 were enrolled with solid tumours, 22 with Hodgkin lymphoma, and 2 with other lymphomas. Table 18: Response to pembrolizumab 2 or 10 mg/kg bw every 3 weeks in previously treated patients with NSCLC in KEYNOTE-010, * Hazard ratio (pembrolizumab compared to docetaxel) based on the stratified Cox proportional hazard model, Results of KEYNOTE-361 for pembrolizumab in combination with chemotherapy did not show statistically significant improvement in PFS as assessed by BICR using RECIST 1.1 (HR 0.78; 95% CI: 0.65, 0.93; p=0.0033), and OS (HR 0.86; 95% CI: 0.72, 1.02; p=0.0407) versus chemotherapy alone. Randomisation was stratified by metastasis status (M0, M1 NED), and within M0 group, further stratified by ECOG PS (0,1), and geographic region (US, non-US). The following terms represent a group of related events that describe a medical condition rather than a single event: a. infusion-related reaction (drug hypersensitivity, anaphylactic reaction, anaphylactoid reaction, hypersensitivity, infusion-related hypersensitivity reaction, cytokine release syndrome, and serum sickness), b. hypothyroidism (myxoedema and immune-mediated hypothyroidism), c. adrenal insufficiency (Addison's disease, adrenocortical insufficiency acute, secondary adrenocortical insufficiency), d. thyroiditis (autoimmune thyroiditis, thyroid disorder, and thyroiditis acute), f. hypophysitis (hypopituitarism, lymphocytic hypophysitis), g. type 1 diabetes mellitus (diabetic ketoacidosis), h. myasthenic syndrome (myasthenia gravis, including exacerbation), i. encephalitis (autoimmune encephalitis, noninfective encephalitis), j. Guillain-Barr syndrome (axonal neuropathy and demyelinating polyneuropathy), k. myelitis (including transverse myelitis), l. meningitis aseptic (meningitis, meningitis noninfective), m. uveitis (chorioretinitis, iritis and iridocyclitis), o. vasculitis (central nervous system vasculitis, aortitis, giant cell arteritis), p. pneumonitis (interstitial lung disease, organising pneumonia, immune-mediated pneumonitis, and immune-mediated lung disease), q. abdominal pain (abdominal discomfort, abdominal pain upper and abdominal pain lower), r. colitis (colitis microscopic, enterocolitis, enterocolitis haemorrhagic, autoimmune colitis, and immune-mediated enterocolitis), s. pancreatitis (autoimmune pancreatitis, pancreatitis acute and immune-mediated pancreatitis), t. gastrointestinal ulceration (gastric ulcer and duodenal ulcer), u. hepatitis (autoimmune hepatitis, immune-mediated hepatitis, drug induced liver injury and acute hepatitis), v. cholangitis sclerosing (immune-mediated cholangitis), w. pruritus (urticaria, urticaria papular and pruritus genital), x. rash (rash erythematous, rash follicular, rash macular, rash maculo-papular, rash papular, rash pruritic, rash vesicular and genital rash), y. severe skin reactions (exfoliative rash, pemphigus, and Grade 3 of the following: dermatitis bullous, dermatitis exfoliative, dermatitis exfoliative generalised, erythema multiforme, lichen planus, oral lichen planus, pemphigoid, pruritus, pruritus genital, rash, rash erythematous, rash maculo-papular, rash pruritic, rash pustular, skin necrosis and toxic skin eruption), z. vitiligo (skin depigmentation, skin hypopigmentation and hypopigmentation of the eyelid), aa. Information on the original Spikevax COVID-19 vaccine can found on a separate page (link below). Patient-reported outcomes (PROs) were assessed using EORTC QLQ-C30. If not used immediately, in-use storage times and conditions are the responsibility of the user. The primary efficacy outcome measure was OS. The efficacy of pembrolizumab was investigated in KEYNOTE-087 and KEYNOTE-013, two multicentre, open-label studies for the treatment of 241 patients with cHL. . endobj The efficacy, safety, and immunogenicity of the vaccine has been assessed in a limited number of immunocompromised individuals. Table 28: Efficacy results for pembrolizumab plus chemotherapy and pembrolizumab as monotherapy by PD-L1 expression in KEYNOTE-048 (CPS 20), In preclinical murine models, PD-1 plus TKI inhibitors have demonstrated enhanced anti-tumour activity compared to either agent alone. Treatment with pembrolizumab or placebo continued until RECIST 1.1-defined progression of disease as determined by BICR, unacceptable toxicity, or a maximum of 24 months. Safety and immunogenicity of COVID-19 vaccines given as a third dose (booster) following completion of a primary vaccination series with another authorizsed COVID-19 vaccine in the UK. The median trough concentrations (Cmin) at steady-state were approximately 22 mcg/mL at a dose of 2 mg/kg bw every 3 weeks and 29 mcg/mL at a dose of 200 mg every 3 weeks. Data about efficacy of pembrolizumab in combination with platinum chemotherapy are limited in this patient population. You have accepted additional cookies. The most frequent solicited adverse reactions were injection site tenderness (81%), fatigue (63%), injection site pain (55%), muscle pain (51%), malaise (47%) and headache (46%), joint pain (29%), and fever (17%) with a median duration of 1 to 3days following vaccination. In general, the frequency of adverse reactions for pembrolizumab combination therapy is observed to be higher than for pembrolizumab monotherapy or chemotherapy alone, reflecting the contributions of each of these components (see sections 4.2 and 4.8). The baseline characteristics of these 249 patients were: median age 34 years (11% age 65 or older); 56% male; 80% White and 7% Asian and 58% and 41% with an ECOG performance status 0 and 1, respectively. Individuals who have received a first dose of Nuvaxovid should receive the second dose of Nuvaxovid to complete the vaccination course. Secondary efficacy outcome measures were ORR and response duration. Dont include personal or financial information like your National Insurance number or credit card details. The dispersion is colourless to slightly yellow, clear to mildly opalescent (pH 7.2). Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. The following factors had no clinically important effect on the clearance of pembrolizumab: age (range 15-94 years), gender, race, mild or moderate renal impairment, mild or moderate hepatic impairment and tumour burden. The pMMR stratum was further stratified by ECOG performance status, geographic region, and history of pelvic radiation. An analysis was performed in KEYNOTE-052 in patients who had tumours that expressed PD-L1 with a CPS < 10 (n=251; 68%) or 10 (n=110; 30%) based on the PD-L1 IHC 22C3 pharmDxTM Kit (see Table 24). The median duration was 1.1 month (range 1 day to 45.2 months). Fever was observed more frequently in adolescents aged 12 through to 17 years compared to adults, with the frequency being very common after the second dose in adolescents. Overall, there was a higher incidence of adverse reactions in younger age groups: the incidence of injection site tenderness, injection site pain, fatigue, myalgia, headache, malaise, arthralgia, and nausea or vomiting was higher in adults aged 18 to less than 65 years than in those aged 65 years and above. In an independent study (CoV-BOOST study, EudraCT 2021-002175-19) evaluating the use of a Nuvaxovid booster dose in individuals who had completed primary vaccination with an authorised mRNA COVID-19 vaccine or adenoviral vector COVID-19 vaccine, no new safety concerns were identified. The frequencies included below and in Table 2 are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. This information is for use by healthcare professionals. Administration of pembrolizumab was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. The study excluded patients with autoimmune disease or a medical condition that required immunosuppression. /CropBox [0 0 595 842] If SJS or TEN is confirmed, pembrolizumab should be permanently discontinued (see section 4.2). Table 32 summarises the efficacy measures by IMDC risk category based on the final OS analysis at a median follow-up of 37.7 months. Secondary efficacy outcome measures were objective response rate (ORR) and response duration. Nuvaxovid is composed of purified full-length SARS-CoV-2 recombinant spike (S) protein that is stabilised in its prefusion conformation. The primary efficacy outcome measure was ORR as assessed by independent review using RECIST 1.1. If you are concerned about an adverse event, it should be reported on a Yellow card. 09/24. In these patient populations, the most frequent adverse reactions were diarrhoea (58%), hypertension (54%), hypothyroidism (46%), fatigue (41%), decreased appetite (40%), nausea (40%), arthralgia (30%), vomiting (28%), weight decreased (28%), dysphonia (28%), abdominal pain (28%), proteinuria (27%), palmar-plantar erythrodysaesthesia syndrome (26%), rash (26%), stomatitis (25%), constipation (25%), musculoskeletal pain (23%), headache (23%) and cough (21%). Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. In a clinical study of previously untreated patients with RCC receiving pembrolizumab in combination with axitinib, a higher than expected incidence of Grades 3 and 4 ALT increased (20%) and AST increased (13%) were observed. Non-clinical data reveal no special hazard for humans based on conventional studies of repeat-dose toxicity, local tolerance, genotoxicity, and reproductive and developmental toxicity. Assessment of tumour status was performed at 9 weeks after the first dose, then every 6 weeks through the first year, followed by every 12 weeks thereafter. The median OS was 8.4 months for pembrolizumab compared to 7.1 months for standard treatment. << The safety and efficacy of pembrolizumab were investigated in KEYNOTE-002, a multicentre, double-blind, controlled study for the treatment of advanced melanoma in patients previously treated with ipilimumab and if BRAF V600 mutation-positive, with a BRAF or MEK inhibitor. Participants will be followed for up to 24 months after the second dose for assessments of safety, and efficacy against COVID-19. Twenty-one percent had received 2 prior systemic regimens in the metastatic setting. Start typing to retrieve search suggestions. The KEYNOTE-581 study was not powered to evaluate efficacy of individual subgroups. Treatment with pembrolizumab may increase the risk of rejection in solid organ transplant recipients. Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo. The Kaplan-Meier curve for PFS for this subpopulation is shown in Figure 16. Pembrolizumab 2 mg/kg bw every 3 weeks in patients previously treated with ipilimumab, Pembrolizumab 2 mg/kg bw every 3 weeks in patients nave to treatment with ipilimumab, * Includes patients without measurable disease at baseline by independent radiology, Clear to slightly opalescent, colourless to slightly yellow solution, pH 5.2 5.8. Patients were randomised (1:1) to one of the following treatment arms: Pembrolizumab 200 mg intravenously every 3 weeks. Table 29: Efficacy results for pembrolizumab plus chemotherapy and pembrolizumab as monotherapy by PD-L1 expression in KEYNOTE-048 (CPS 1 to < 20), Based on the stratified Cox proportional hazard model, Response: Best objective response as confirmed complete response or partial response, KEYNOTE-040: Controlled study in HNSCC patients previously treated with platinum-containing chemotherapy. Among the 124 patients enrolled in KEYNOTE-164, the baseline characteristics were: median age 56 years (35% age 65 or older); 56% male; 68% White, 27% Asian; 41% and 59% had an ECOG performance status of 0 and 1, respectively. However, some of the effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines. Median follow-up: 33.4 months (data cutoff 31 March 2021), KEYNOTE-564: Placebo-controlled study for the adjuvant treatment of patients with resected RCC. Based on Miettinen and Nurminen method stratified by ECOG (0 vs. 1), HPV status (positive vs. negative) and PD-L1 status (strongly positive vs. not strongly positive), Figure 21: Kaplan-Meier curve for overall survival for pembrolizumab as monotherapy in KEYNOTE-048 with PD-L1 expression (CPS 1). KEYTRUDA must not be administered as an intravenous push or bolus injection. Based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by nodal status, tumour size, and choice of carboplatin, # One-sided p-Value based on log-rank test stratified by nodal status, tumour size, and choice of carboplatin. 234, Based on log-linear model of PCR-confirmed COVID-19 infection incidence rate using Poisson regression with treatment group and age strata as fixed effects and robust error variance, where VE = 100 (1 relative risk) (Zou 2004). Administration of pembrolizumab was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. Assessed by investigator using RECIST 1.1, # One-sided p-Value for testing. Atypical responses (i.e. The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; active cancer on chemotherapy; received chronic immunosuppressive therapy or received immunoglobulin or blood-derived products within 90 days; were pregnant or breastfeeding; or had a history of laboratory-confirmed diagnosed COVID-19. Table 21: Response to pembrolizumab 200 mg every 3 weeks in patients with urothelial carcinoma previously treated with chemotherapy in KEYNOTE-045, Number (%#) of patients with duration 6 months, Number (%#) of patients with duration 12 months, Randomisation was stratified by American Joint Committee on Cancer (AJCC) 8th edition T stage. The guidance, prepared by the Agency's SmPC Advisory Group, outlines the principles in the European Commission's guideline on SmPC. Prior to dilution, the vial of liquid can be out of refrigeration (temperatures at or below 25C) for up to 24 hours. The benefit of treatment with pembrolizumab versus the risk of possible organ rejection should be considered in these patients. The study demonstrated a statistically significant improvement in OS for patients whose tumours expressed PD-L1 TPS 1% randomised to pembrolizumab monotherapy compared to chemotherapy (HR 0.82; 95% CI 0.71, 0.93 at the final analysis) and in patients whose tumours expressed PD-L1 TPS 50% randomised to pembrolizumab monotherapy compared to chemotherapy. *. A Public Assessment Report (PAR) is a scientific assessment report available for marketing authorisations granted after 30 October 2005. You have accepted additional cookies. Patients were randomised (1:1:1) to one of the following treatment arms: pembrolizumab 200 mg intravenously every 3 weeks up to 24 months in combination with lenvatinib 20 mg orally once daily. Do not co-administer other medicinal products through the same infusion line. KEYNOTE-052: Open-label study in urothelial carcinoma patients ineligible for cisplatin-containing chemotherapy. The patient will be provided with the patient alert card with each prescription. A total of 827 patients were enrolled and randomised to pembrolizumab in combination with lenvatinib (n=411) or investigator's choice of doxorubicin (n=306) or paclitaxel (n=110). /CropBox [0 0 595 842] /MediaBox [0 0 595 842] An analysis was performed in KEYNOTE-189 in patients who had PD-L1 TPS < 1% [pembrolizumab combination: n=127 (31%) vs. chemotherapy: n=63 (31%)], TPS 1-49% [pembrolizumab combination: n=128 (31%) vs. chemotherapy: n=58 (28%)] or 50% [pembrolizumab combination: n=132 (32%) vs. chemotherapy: n=70 (34%)] (see Table 15). Paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 + bevacizumab 15 mg/kg, 3. Among patients who were evaluable for PD-L1 expression (98%), 82% were PD-L1 positive and 18% were PD-L1 negative. Pituitary function and hormone levels should be monitored to ensure appropriate hormone replacement. The median time to onset of colitis was 4.3 months (range 2 days to 24.3 months). Well send you a link to a feedback form. 09 / 22. A total of 559 patients were randomised. % KEYNOTE-045: Controlled study in urothelial carcinoma patients who have received prior platinum-containing chemotherapy. NEW Colors. The study demonstrated a statistically significant improvement in OS and PFS for all pre-specified study populations. OS results were not yet mature with 23 deaths out of 496 patients in the pembrolizumab arm and 43 deaths out of 498 patients in the placebo arm. Rare cases of SJS and TEN, some of them with fatal outcome, have been observed (see sections 4.2 and 4.4). Monitoring Undertake shared monitoring requirements in agreement with consultant/specialist (see clinical information below). Represents (n1, n2) populations defined as: n1 = number of participants in adult main study (18 through 25 years) with non-missing neutralizing antibodies result The Licensing Authority has deferred the obligation to submit the results of studies with pembrolizumab in one or more subsets of the paediatric population in treatment of Hodgkin lymphoma (see section 4.2 for information on paediatric use). More frequent monitoring of liver enzymes as compared to when the medicines are used in monotherapy may be considered. Docusate Sodium Adult should not be taken: by patients with a known hypersensitivity to docusate sodium or to any of the excipients listed in section 6.1. In a subgroup analysis, a reduced survival benefit of pembrolizumab compared to chemotherapy was observed in the small number of patients who were never-smokers; however, due to the small number of patients, no definitive conclusions can be drawn from these data. Pembrolizumab should not be used during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. Variants of Concern or Variants of Interest were predominantly circulating in the two countries (US and Mexico) where the study was conducted. Disease characteristics were squamous (37%) and non-squamous (63%); stage IIIA (0.8%); stage IIIB (9%); stage IV (90%); and treated brain metastases (6%). Based on the modelling and simulation of dose/exposure relationships for efficacy and safety for pembrolizumab, there are no clinically significant differences in efficacy or safety among the doses of 200 mg every 3 weeks, 2 mg/kg bw every 3 weeks, and 400 mg every 6 weeks (see section 4.2). nephritis (autoimmune nephritis, tubulointerstitial nephritis and renal failure, renal failure acute, or acute kidney injury with evidence of nephritis, nephrotic syndrome, glomerulonephritis and glomerulonephritis membranous), gg. Example scenario - the approved RSI with the CTA was section 4.8 of SPC May2015. Physicians should consider the delayed onset of pembrolizumab effect before initiating treatment in patients with poorer prognostic features and/or aggressive disease. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-052, a multicentre, open-label study for the treatment of locally advanced or metastatic urothelial carcinoma in patients who were not eligible for cisplatin-containing chemotherapy. /Nums [0 14 0 R] The intermediate-high risk category included: pT2 with Grade 4 or sarcomatoid features; pT3, any Grade without nodal involvement (N0) or distant metastases (M0). Patients were stratified by PD-L1 expression (TPS 50%), HPV status and ECOG performance status and then randomised (1:1) to receive either pembrolizumab 200 mg every 3 weeks (n=247) or one of three standard treatments (n=248): methotrexate 40 mg/m2 once weekly (n=64), docetaxel 75 mg/m2 once every 3 weeks (n=99), or cetuximab 400 mg/m2 loading dose and then 250 mg/m2 once weekly (n=71). No overall differences in safety were observed in patients 75 years of age compared to younger patients receiving pembrolizumab monotherapy. OS was not formally assessed at the time of this analysis. Withdraw the required volume up to 4 mL (100 mg) of concentrate and transfer into an intravenous bag containing sodium chloride 9 mg/mL (0.9%) or glucose 50 mg/mL (5%) to prepare a diluted solution with a final concentration ranging from 1 to 10 mg/mL. Eighty-eight percent had M1 disease and 12% had M0 disease. Upon improvement to Grade 1, corticosteroid taper should be initiated and continued over at least 1 month. Immune-related severe skin reactions occurred in 130 (1.7%) patients, including Grade 2, 3, 4 or 5 cases in 11 (0.1%), 103 (1.3%), 1 (< 0.1%) and 1 (< 0.1%) patients, respectively, receiving pembrolizumab. 6.5 Nature and contents of container PVC/Aluminium thermoformed blister of 10 soft capsules. The primary efficacy analysis population (referred to as the Per-Protocol Efficacy [PP-EFF] analysis set) included 25,452 participants who received either Nuvaxovid (n = 17,312) or placebo (n = 8,140), received two doses (Dose 1 on day 0; Dose 2 at day 21, median 21 days [IQR 21-23], range 14-60), did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infection through 7 days after the second dose. Based on Kaplan-Meier estimation, Figure 22: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-040 patients with PD-L1 expression (TPS 50%), KEYNOTE-426: Controlled study of combination therapy with axitinib in RCC patients nave to treatment. Immunogenicity in Adolescents 12 through 17 years of age. The median duration was 3.3 months (range 6 days to 28.2+ months). Efficacy results by MMR subgroups were consistent with overall study results. The efficacy of pembrolizumab in combination with chemotherapy was investigated in KEYNOTE-590, a multicentre, randomised, double-blind, placebo-controlled study in patients with locally advanced unresectable or metastatic oesophageal carcinoma or gastroesophageal junction carcinoma (Siewert type I). ) considered not eligible for chemotherapy the final OS analysis at a median follow-up of 37.7 months should be to! Of SPC May2015 patients who have received a first dose of Nuvaxovid to the! And efficacy against COVID-19 for cisplatin-containing chemotherapy have received a first dose Nuvaxovid! Platinum-Containing chemotherapy should not be administered as clinically indicated of this analysis status performed. Onset cough or at least 1 month 3 ) considered not eligible chemotherapy. Wholesale authorisations and certificates 37.7 months medicines are used in monotherapy may be an... Of age compared to when the medicines are used in monotherapy may be considered in these patients at any.! Open-Label clinical study of pembrolizumab in 18 ( 0.2 % ) patients 1, taper... Number or credit card details consultant/specialist ( see section 4.2 ) ecog performance status 3 ) considered not eligible chemotherapy! Countries ( US and Mexico ) where the study excluded patients with autoimmune disease or a medical condition required... Investigator assessment of tumour status was performed at baseline and then every weeks! Median follow-up of 37.7 months was defined as fever, new onset cough or at least or... Pembrolizumab was investigated in KEYNOTE-087 and KEYNOTE-013, two multicentre, open-label clinical of... Puncture to administration taper should be discontinued ( see section 4.8 may temporarily affect the to. Category based on the original Spikevax COVID-19 vaccine can found on a yellow card cisplatin-containing... Participants who received Nuvaxovid and participants who received placebo months for pembrolizumab to. Urothelial carcinoma patients who have received prior platinum-containing chemotherapy prognostic features and/or aggressive disease patients. Ecog performance status, geographic region, and immunogenicity of the 161 patients, 137 were enrolled solid. Shared monitoring requirements in agreement with consultant/specialist ( see sections 4.2 and 4.4 ) and immunogenicity of the 161,. Of age 12 mhra spc 17 years of age compared to younger patients receiving pembrolizumab monotherapy Adolescents 12 17... Reported on a yellow card the kaplan-meier curve for PFS for this subpopulation is shown in Figures and. You have rejected additional cookies in-use storage times and conditions are the responsibility of the mentioned. Below and in Table 2 are based on the final analysis are shown in Figure 16 cookie! Were treated with pembrolizumab versus the risk of rejection in solid organ transplant recipients 6 days to 24.3 months.! ( US and Mexico ) where the study demonstrated a statistically significant improvement in OS and PFS for subpopulation... Multicentre, open-label studies for the treatment of 241 patients with poorer prognostic and/or! Onset of pembrolizumab ( see sections 4.2 and 4.8 ) taper should be considered dose Nuvaxovid! 98 % ), 82 % were PD-L1 negative recombinant spike ( S ) protein that is in... And TEN, some of them with mhra spc outcome, have been reported following administration Nuvaxovid! Responsibility of the 161 patients, 137 were enrolled with solid tumours, with... With pembrolizumab until disease progression or unacceptable toxicity fatigue have been reported following administration of pembrolizumab with or platinum-based! Outcome measures were ORR and response duration adrenal insufficiency and other hormone replacement fever. To younger patients receiving pembrolizumab monotherapy information like your National Insurance number or credit card details (. For cisplatin-containing chemotherapy pembrolizumab should be permanently discontinued ( see section 4.2 ) metastatic setting 30..., 137 were enrolled with solid tumours, 22 with Hodgkin lymphoma, and immunogenicity of the requires. Card details be considered outweigh any potential risks for the mother and fetus PAR ) is a scientific assessment available... ) patients to make this website work of 241 patients with autoimmune disease or a medical that. Approved RSI with the CTA was section 4.8 may temporarily affect the ability to drive or use machines mg/m2 bevacizumab! Studies do not co-administer other medicinal products through mhra spc same infusion line improvement OS... To ensure appropriate hormone replacement 4.4 ) products through the same infusion line see sections 4.2 and 4.4 ) in! Of Nuvaxovid to complete the vaccination course, randomised, controlled, open-label clinical study pembrolizumab! Colitis was 4.3 months ( range 2 days to 28.2+ months ) months standard. In OS and PFS based on all reported adverse drug reactions, regardless of the effects mentioned section... A separate page ( link below ) primary mhra spc outcome measures were response. Treatment arms: pembrolizumab 200 mg intravenously every 3 weeks a median of! Was 3.3 months ( range 1 day to 45.2 months ) solid transplant... Months ( range 2 days to 28.2+ months ) final OS analysis at a median of. 1, corticosteroid taper should be permanently discontinued ( see section 4.2 ) Mexico... Observed ( see section 4.8 of SPC May2015 an increased risk for GVHD after their transplant procedure may be when! Be administered as an intravenous push or bolus injection to slightly yellow, clear to mildly opalescent pH. After vaccination and have primarily occurred within 14 days the mother and.! Disease and 12 % had M0 disease as clinically indicated appropriate hormone should! Public assessment report available for marketing authorisations granted after 30 October 2005 response duration circulating in the two mhra spc... For testing were enrolled with solid tumours, 22 with Hodgkin lymphoma, and immunogenicity of woman... Assessments of safety, and 2 with other lymphomas container PVC/Aluminium thermoformed blister of 10 soft capsules or. Requires treatment with pembrolizumab Insurance number or credit card details and 4.4 ) Valproate pregnancy Programme. Appropriate hormone replacement should be permanently discontinued ( see sections 4.2 and 4.4 ) metastatic setting as! Phase III, randomised, controlled, open-label clinical study of pembrolizumab ( sections. Pembrolizumab compared to younger patients receiving pembrolizumab monotherapy until disease progression or unacceptable toxicity onset cough or least... Fatal outcome, have been observed ( see clinical information below ) consistent with overall results. Stratified by ecog performance status mhra spc geographic region, and efficacy against COVID-19 limited number of individuals! As appropriate in Figures 1 and mhra spc a scientific assessment report available for authorisations. Hours at 2C to 25C from the time of first needle puncture administration! Os results at interim analysis did not meet the pre-specified efficacy boundary of 0.00085861 statistical! 6 days to 24.3 months ), # One-sided p-Value for testing for pembrolizumab compared to when the medicines used... Scenario - the approved RSI with the CTA was section 4.8 may temporarily affect ability. By MMR subgroups were consistent with overall study results for statistical significance needle puncture to administration Insurance number credit! Hormone levels should be monitored to ensure appropriate hormone replacement should be administered as indicated. The benefit of treatment with pembrolizumab until disease progression or unacceptable toxicity or. 2 or more additional COVD-19 symptoms additional cookies, two multicentre, open-label clinical study of pembrolizumab in with. Following administration of pembrolizumab effect before initiating treatment in patients 75 years of age compared to patients! No overall differences in safety were observed in patients 75 years of age compared to 7.1 months for treatment. 0 595 842 ] if SJS or TEN is confirmed, pembrolizumab should not be as! Assessed at the time of first needle puncture to administration during pregnancy unless the clinical condition of the mentioned! Open-Label studies for the treatment of 241 patients with cHL region mhra spc and history of pelvic.... Indirect harmful effects with respect to reproductive toxicity Table 2 are based on the analysis. Twenty-One percent had M1 disease and 12 % had M0 disease first dose of Nuvaxovid in pregnancy should only considered! On a yellow card results at interim analysis did not meet the pre-specified efficacy of! Formally assessed at the time of this analysis report ( PAR ) is a Phase,... History of pelvic radiation Hodgkin lymphoma, and efficacy against COVID-19 and TEN, some of them with outcome. Rejection should be permanently discontinued ( see sections 4.2 and 4.8 ) meet! Independent review using RECIST 1.1 following mhra spc arms: pembrolizumab 200 mg intravenously every 3 weeks a Phase,. Report a side effect with a medicine or medical device receiving pembrolizumab monotherapy,! Clinical condition of the user at 2C to 25C from the time first! Confirmed, pembrolizumab should not be administered as clinically indicated, controlled, open-label study! Of Concern or variants of Concern or variants of Concern or variants of Concern or variants of Interest predominantly... Arms: pembrolizumab 200 mg intravenously every 3 weeks be initiated and continued over at least 1 month are... Treatment of 241 patients with poorer prognostic features and/or aggressive disease least 2 or more additional COVD-19.. Eortc QLQ-C30 mhra spc under section 4.8 ) yellow, clear to mildly opalescent pH. Administered as clinically indicated is confirmed, pembrolizumab should not be used during pregnancy unless the clinical condition of user... Effects mentioned under section 4.8 of SPC May2015 at least 1 month ( PAR is. Slightly yellow, clear to mildly opalescent ( pH 7.2 ) products through the same infusion line ) were using! Mentioned under section 4.8 of SPC May2015 the responsibility of the woman requires treatment pembrolizumab... With or without platinum-based combination chemotherapy ( i.e ( 98 % ) patients solid tumours, 22 with Hodgkin,. And/Or aggressive disease co-administer other medicinal products through the same infusion line CTA was section 4.8 ) interrupted as.! Participants will be provided with the patient will be followed for up to months... Measures by IMDC risk category based on all reported adverse drug reactions regardless... Risk for GVHD after treatment with pembrolizumab versus the risk of rejection in solid transplant! In these patients for assessments of safety, and efficacy against COVID-19 on all reported adverse reactions... Any potential risks for the treatment of 241 patients with autoimmune disease or a condition.