Efficacy results by MSKCC prognostic group are summarised in Table 34. 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. Novavax CZ a.s. 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. This agency is responsible for MHRA audits throughout the world. Neutralising antibody titers measured by a wild-type assay were assessed 28 days post-booster dose. Assessment of tumour status was performed every 8 weeks. This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially sodium-free. No specific factor(s) associated with early deaths could be identified. Based on Miettinen and Nurminen method stratified by MMR Status, ECOG performance status, geographic region, and history of pelvic radiation, Figure 36: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-775 (intent to treat population), Figure 37: Kaplan-Meier curve for progression free-survival by treatment arm in KEYNOTE-775 (intent to treat population). Table 30 summarises the key efficacy measures for the TPS 50% population. In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Pembrolizumab is most commonly associated with immune-related adverse reactions. Clear to slightly opalescent, colourless to slightly yellow solution, pH 5.2 5.8. Among 370 patients with urothelial carcinoma who were not eligible for cisplatin-containing chemotherapy baseline characteristics were: median age 74 years (82% age 65 or older); 77% male; and 89% White and 7% Asian. Randomisation was stratified by chemotherapy treatment (paclitaxel or nab-paclitaxel vs. gemcitabine and carboplatin), tumour PD-L1 expression (CPS 1 vs. CPS < 1), and prior treatment with the same class of chemotherapy in the neoadjuvant setting (yes vs. no). COVID-19 was defined as first episode of PCR-confirmed mild, moderate, or severe COVID-19 with at least one or more of the predefined symptoms within each severity category. /MediaBox [0 0 595 842] 15 0 obj Secondary efficacy outcome measures were duration of response, PFS, and OS. /Rotate 0 In KEYNOTE-042, a higher number of deaths within 4 months of treatment initiation followed by a long-term survival benefit was observed with pembrolizumab monotherapy compared to chemotherapy (see section 5.1). BRAF mutations were reported in 13% of the study population. 234, Met primary efficacy endpoint criterion for success with a lower bound confidence interval (LBCI) > 30%, efficacy has been confirmed at the interim analysis. Nephritis resolved in 20 patients, 5 with sequelae. The assessment of efficacy and immunogenicity of Nuvaxovid in adolescent participants 12 through 17years of age occurred in the United States in the ongoing paediatric expansion portion of the Phase 3 multicentre, randomised, observer-blinded, placebo-controlled 2019nCoV-301 study. Updated efficacy results with a median follow-up time of 45.5 months are summarised in Table 11 and Figures 6 and 7. All but one patient was white. KEYTRUDA as monotherapy is indicated for the treatment of adults and adolescents aged 12 years and older with advanced (unresectable or metastatic) melanoma. This vaccine should be handled by a healthcare professional using aseptic techniques to ensure the sterility of each dose. Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo. stream Pharmacotherapeutic group: Vaccine, other viral vaccines, ATC code: J07BX03. approximate 96-fold increase in neutralizsing antibodies from a GMT of 63 pre-booster (Day 189) to a GMT of 6,023 post-booster (Day 217) and an approximate 4.1-fold increase from a peak GMT (14 days post-Dose 2) of 1,470. Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity or disease progression. If specified in the indication, patient selection for treatment with KEYTRUDA based on MSI-H/dMMR tumour status should be confirmed by a validated test (see sections 4.1 and 5.1). Altitude above sea level (m) 7. In patients treated with pembrolizumab in combination with axitinib or lenvatinib (n=1,456), the incidence of hypothyroidism was 46.2% (all Grades) with 0.8% Grade 3 or 4. Expires . endobj Manufacturers of all affected formulations of ranitidine have been instructed 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. Email Address: Registration No: Adverse reactions were usually mild to moderate in severity with a median duration of less than or equal to 2 days for local events and less than or equal to 1 day for systemic events following vaccination. Data for the following immune-related adverse reactions are based on patients who received pembrolizumab across four doses (2 mg/kg bw every 3 weeks, 10 mg/kg bw every 2 or 3 weeks, or 200 mg every 3 weeks) in clinical studies (see section 5.1). Hazard ratio (pembrolizumab combination therapy compared to chemotherapy) based on the stratified Cox proportional hazard model. KEYTRUDA, as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma in adults whose tumours express PD-L1 with a CPS 1 (see section 5.1). All patients had M1 disease. 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. We publish the most up-to-date information for a medicine according to its licence history. At the earlier pre-specified final analysis of ORR (median follow-up time of 17.3 months), statistically significant superiority was achieved for ORR comparing pembrolizumab plus lenvatinib with sunitinib, (odds ratio: 3.84 [95% CI: 2.81, 5.26], p-Value< 0.0001). The primary efficacy outcome measures were OS and PFS as assessed by the investigator according to RECIST 1.1 in squamous cell histology, CPS 10, and in all patients. 14 0 obj Results reported from the pre-specified final analysis for RFS at a median follow-up of 20.5 months are summarised in Table 10 and Figure 4. The frequencies are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. Atypical responses (i.e. Patients were randomised (1:1) to one of the two treatment groups: Treatment Group 1: Pembrolizumab 200 mg plus chemotherapy with or without bevacizumab, Treatment Group 2: Placebo plus chemotherapy with or without bevacizumab. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/fetal development, parturition, or post-natal development (see section 5.3). See Table 25 and Figures 18 and 19. It is used by healthcare professionals, such as doctors, nurses and pharmacists. The incidences of immune-related adverse reactions were 36.1% all Grades and 8.9% for Grades 3-5 for pembrolizumab monotherapy in the adjuvant setting (n=1,480) and 24.2% all Grades and 6.4% for Grades 3-5 in the metastatic setting (n=5,375). Disease characteristics were squamous (37%) and non-squamous (63%); stage IIIA (0.8%); stage IIIB (9%); stage IV (90%); and treated brain metastases (6%). *, KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous non-small cell lung carcinoma in adults. Updated efficacy results with a median follow-up time of 29.7 months are summarised in Table 35 and Figure 27. If the outcome of the inspection is that the manufacturer does not comply, a statement of non-compliance may be issued and entered into MHRA-GMDP. The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products. HWS6_Hb,GKBLg;Nmva~i?~>Fvq59>LDz1b'~: X.i5jNq].gS1 k$~yr;_6Z\!*'+0W0SY3FuHI43#}l|Q~pg$S)-HPWl8{{n/f:9 9c(|2(?f`o$8H,$4E<>sQQvAck2eShaEx:o`lP7r4kDqk2E9adV&! *. Table 9: Efficacy results by PD-L1 expression in KEYNOTE-006. A total of 1,173 participants (PP-IMM Analysis Set) received a booster dose of Nuvaxovid approximately 6months after completion of the primary series of Nuvaxovid (Day201). Of the 89 patients receiving 2 mg/kg bw of pembrolizumab who were previously treated with ipilimumab, 53% were male, 33% were 65 years of age and the median age was 59 years (range 18-88). The guidance, prepared by the Agency's SmPC Advisory Group, outlines the principles in the European Commission's guideline on SmPC. an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. Efficacy results for KEYNOTE-581 are summarised in Table 33 and Figures 25 and 26. One patient experienced engraftment syndrome post-transplant. As expected for an antibody, pembrolizumab does not bind to plasma proteins in a specific manner. The companies those comply their GMP regulations can export their pharmaceutical products to UK. The median time to onset of colitis was 4.3 months (range 2 days to 24.3 months). Monitor for the development or worsening Patients treated with KEYTRUDA must be given the patient alert card and be informed about the risks of KEYTRUDA (see also package leaflet). Counsel patient to report side effects from amiodarone treatment and to protect skin from sunlight. Secondary efficacy outcome measures were ORR and response duration, as assessed by BICR using RECIST 1.1. This publication is licensed under the terms of the Open Government Licence v3.0 except where otherwise stated. /Parent 3 0 R Vaccine efficacy of Nuvaxovid to prevent the onset of COVID-19 from seven days after Dose 2 was 90.4% (95% CI 82.9 94.6). Treatment with pembrolizumab and lenvatinib continued until RECIST v1.1-defined progression of disease as verified by BICR, unacceptable toxicity, or for pembrolizumab, a maximum of 24 months. 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 20: Kaplan-Meier curve for overall survival for pembrolizumab plus chemotherapy in KEYNOTE-048 with PD-L1 expression (CPS 1), Table 27: Efficacy results for pembrolizumab as monotherapy in KEYNOTE-048 with PD-L1 expression (CPS 1), Every medicine pack includes a patient information leaflet (PIL), which provides information on using the medicine safely. Use of pembrolizumab for treatment of patients with advanced or recurrent MSI-H or dMMR endometrial carcinoma. SPC Flooring Marble. In patients with cHL, the incidence of pneumonitis (all Grades) ranged from 5.2% to 10.8% for cHL patients in KEYNOTE-087 (n=210) and KEYNOTE-204 (n=148), respectively. The median duration was 3.3 months (range 6 days to 28.2+ months). Among the 304 patients in KEYNOTE-204, there is a subpopulation consisting of 112 patients who failed a transplant before enrolling and 137 who failed 2 or more prior therapies and were ineligible for ASCT at the time of enrolment. Use within 6 hours after first puncture. Frequencies are defined as: very common ( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be estimated from the available data). 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. The primary efficacy outcome was PFS and the secondary efficacy outcome measure was ORR, both assessed by BICR according to the 2007 revised International Working Group (IWG) criteria. 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. No dose reductions of KEYTRUDA are recommended. Of 14 patients in KEYNOTE-013 who proceeded to allogeneic HSCT after treatment with pembrolizumab, 6 patients reported acute GVHD and 1 patient reported chronic GVHD, none of which were fatal. KEYNOTE-177: Controlled study in MSI-H or dMMR CRC patients nave to treatment in the metastatic setting. The study demonstrated a statistically significant improvement in OS for all patients randomised to pembrolizumab in combination with chemotherapy compared to standard treatment (HR 0.72; 95% CI 0.60-0.87) and in patients whose tumours expressed PD-L1 CPS 1 randomised to pembrolizumab monotherapy compared to standard treatment. Seventy percent had at least two and 35% of patients had three or more prior systemic therapies for advanced melanoma. Use of pembrolizumab in urothelial carcinoma patients who have received prior platinum-containing chemotherapy. Cardiology SPC abbreviation meaning defined here. 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. Chemotherapy could continue per standard of care. $>H}X@z%|!T|W=^ewx LcX/)PeIe61Knwszc`A[Av}pS*]?u5-QVe hU!y?4-03,1u#cWZS$Sm,^k]z?(w9/nWg9. 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. EFS was defined as the time from randomisation to the first occurrence of any of the following events: progression of disease that precludes definitive surgery, local or distant recurrence, second primary malignancy, or death due to any cause. Close observation for at least 15 minutes is recommended following vaccination. Based on Kaplan-Meier estimation, Figure 18: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-361 (intent to treat population, choice of carboplatin), Figure 19: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-361 (patients with PD-L1 expression CPS 10, intent to treat population, choice of carboplatin), KEYNOTE-048: Controlled study of monotherapy and combination therapy in HNSCC patients nave to treatment in the recurrent or metastatic setting. Thirty-one percent had an ECOG Performance Status of 1, 69% had ECOG Performance Status of 0 and 32% had elevated LDH. /Length 29 0 R No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. Discard this vaccine if not used within 6 hours after first puncture of the vial, see section 6.3. /Parent 3 0 R 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). Administration of pembrolizumab was permitted beyond RECIST-defined disease progression by BICR or beyond discontinuation of pemetrexed if the patient was clinically stable and deriving clinical benefit as determined by the investigator. PILs are based on the Summaries of Product Characteristics (SPCs) which are a description of a medicinal products properties and the conditions attached to its use. /CropBox [0 0 595 842] If SJS or TEN is confirmed, pembrolizumab should be permanently discontinued (see section 4.2). Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates for male and female participants and racial groups, and across participants with medical comorbidities associated with high risk of severe COVID-19. Pembrolizumab is a humanised monoclonal anti-programmed cell death-1 (PD-1) antibody (IgG4/kappa isotype with a stabilising sequence alteration in the Fc region) produced in Chinese hamster ovary cells by recombinant DNA technology. !B&| 38apbfgkW% _oo.q9,Np$Jh'@y+Gb1,]7E?p!])~b? included in other section of SPC. Secondary efficacy outcome measures were duration of response, PFS and OS. << Name of the medicinal product 2. A Periodic Safety Update Report (PSUR) is a document which provides an evaluation of the risk-benefit balance of the medicine at defined times following authorisation. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD-L1 with a combined positive score (CPS) 10 (see section 5.1). stream endstream endstream For liver enzyme elevations, in patients with RCC being treated with KEYTRUDA in combination with axitinib: If ALT or AST 3 times ULN but < 10 times ULN without concurrent total bilirubin 2 times ULN, both KEYTRUDA and axitinib should be withheld until these adverse reactions recover to Grades 0-1. Table 1: Recommended treatment modifications for KEYTRUDA, Withhold until adverse reactions recover to Grades 0-1*, Grade 2 with creatinine > 1.5 to 3 times upper limit of normal (ULN), Grade 2 adrenal insufficiency and hypophysitis, Withhold treatment until controlled by hormone replacement, Grades 3 or 4 adrenal insufficiency or symptomatic hypophysitis, Type 1 diabetes associated with Grade 3 hyperglycaemia (glucose > 250 mg/dL or > 13.9 mmol/L) or associated with ketoacidosis. 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. There are limited data on the safety and efficacy of KEYTRUDA in patients with ocular melanoma (see section 5.1). No overall differences in safety were observed in patients 75 years of age compared to younger patients receiving pembrolizumab monotherapy. The M1 NED category included patients with metastatic disease who had undergone complete resection of primary and metastatic lesions. An updated OS analysis was performed when patients receiving pembrolizumab and lenvatinib or sunitinib had a median survival follow-up of 33.4 months. For instructions on handling and disposal of the vaccine, see section 6.6. A total of 254 participants received two doses of Nuvaxovid (0.5mL 3weeks apart) as the primary vaccination series. Hazard ratio (pembrolizumab compared to chemotherapy) based on the stratified Cox proportional hazard model. Assessment of tumour status was performed every 9 weeks through the first year, then every 12 weeks thereafter. H0: difference in % = 0 versus H1: difference in % > 0. Based on Miettinen and Nurminen method stratified by PD-L1 status, platinum chemotherapy and smoking status, Figure 11: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-189 (intent to treat population), Figure 12: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-189 (intent to treat population). endobj Use of pembrolizumab in combination with chemotherapy. Pembrolizumab should be withheld for Grade 3 until recovery to Grade 1 hyperthyroidism. version of this document in a more accessible format, please email, Check benefits and financial support you can get, Find out about the Energy Bills Support Scheme, Marketing authorisations, variations and licensing guidance, Medicines and Healthcare products Regulatory Agency, Last updated 12/22 - Summary of Product Characteristics Spikevax bivalent Original/Omicron, Last updated 12/22 - Patient Information Leaflet Spikevax bivalent Original/Omicron, Spikevax bivalent Original/Omicron Information for Healthcare Professionals (Regulation 174), Spikevax bivalent Original/Omicron Patient Information Leaflet (Regulation 174), Public Assessment Report for Spikevax bivalent Original/Omicron, Last updated 2/23 - Patient Information Leaflet Spikevax bivalent Original/Omicron BA4-5 multi-dose vial, Last updated 2/23 - Summary of Product Characteristics bivalent Original/Omicron BA.4/5 multi-dose vial, Last updated 2/23 - Patient Information Leaflet Spikevax bivalent Original/Omicron BA4-5 single dose vial, Last updated 2/23 - Summary of Product Chacteristics Spikevax bivalent Original/Omicron BA.4/5 single dose vial. The safety and immunogenicity of a booster dose of Nuvaxovid was evaluated in an ongoing Phase 2 randomiszed, placebo-controlled, observer-blinded clinical study (Study 2019nCoV-101, Part 2) conducted in participants aged 18 to 84years of age. Pneumonitis has been reported in patients receiving pembrolizumab (see section 4.8). We use some essential cookies to make this website work. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. /CropBox [0 0 595 842] All patients had a tumour histology of adenocarcinoma. Patients should be monitored for changes in thyroid function (at the start of treatment, periodically during treatment and as indicated based on clinical evaluation) and clinical signs and symptoms of thyroid disorders. All participants were offered the opportunity to continue to be followed in the study. The median number of prior lines of therapy administered for the treatment of cHL was 4 (range 1 to 12). Sixty-five percent of patients had M1c stage, 9% had a history of brain metastases, 66% had no and 34% had one prior therapy. Store the opened vial between 2C to 25C for up to 6 hours after first puncture, see section 6.3. 6 0 obj When pembrolizumab is administered in combination with axitinib or lenvatinib, refer to the SmPC for axitinib or lenvatinib prior to initiation of treatment. The median time to onset of ALT increased was 2.3 months (range: 7 days to 19.8 months). 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. 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). Among the 22 patients with biliary cancer, the baseline characteristics were: median age 61 years (range: 40 to 77); 41% age 65 or older; 73% male, 91% White, 9% Asian; ECOG PS 0 (45%) and 1 (55%); and 82% M1 disease and 18% M0 disease. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-010, a multicentre, open-label, controlled study for the treatment of advanced NSCLC in patients previously treated with platinum-containing chemotherapy. >> Animal fertility studies have not been conducted with pembrolizumab. Participants are being followed for up to 12 months after the primary vaccination series for assessments of safety and efficacy against COVID-19. The recommended dose is a single 500 mg intravenous infusion administered following dilution (see sections 4.4 and 6.6). One patient experienced engraftment syndrome post-transplant. Placebo and carboplatin AUC 6 mg/mL/min on Day 1 of each 21-day cycle for 4 cycles and paclitaxel 200 mg/m2 on Day 1 of each 21-day cycle for 4 cycles or nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 of each 21-day cycle for 4 cycles, followed by placebo every 3 weeks. Patients were randomised (1:1) to one of the following treatment arms: pembrolizumab 200 mg intravenously every 3 weeks in combination with lenvatinib 20 mg orally once daily. Patients with active autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible for the study. Assessment of tumour status was performed every 9 weeks. Nephritis led to discontinuation of pembrolizumab in 17 (0.2%) patients. Adrenal insufficiency (primary and secondary) has been reported in patients receiving pembrolizumab. /Rotate 0 ; Ng:F7|h2F Gpjoh)XmVDU8Zi3Cfp]{gS%-/-"7fAf=0^^s`0Zh8{$M{Yo4=fIVh I>$ s Terms and Conditions Opens in new window | Privacy Notice Opens in new window, Click on this link to navigate to www.mhra.gov.uk, Good Manufacturing Practice (GMP) certificates, Good Distribution Practice Certificates (GDP). This updated OS analysis was not adjusted to account for subsequent therapies. NEW Colors. Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. Patients randomised to pembrolizumab were permitted to continue beyond the first RECIST v1.1-defined disease progression if clinically stable until the first radiographic evidence of disease progression was confirmed at least 4 weeks later with repeat imaging. All patients received pembrolizumab for a median of 4 doses (range 1-35 doses), with 138 patients (85.7%) receiving pembrolizumab for 2 doses or more. Patients were randomised (1:1:1) to receive pembrolizumab at a dose of 2 (n=344) or 10 mg/kg bw (n=346) every 3 weeks or docetaxel at a dose of 75 mg/m2 every 3 weeks (n=343) until disease progression or unacceptable toxicity. Advanced melanoma handling and disposal of the study population of 1, 69 % had ECOG Performance of... The frequencies are based on all reported adverse drug reactions, regardless of Open. Store the opened vial between 2C to 25C for up to 6 hours after puncture. Frequencies are based on the safety and efficacy of KEYTRUDA in patients with initial evidence of progression... Elevated LDH were observed in patients receiving pembrolizumab and lenvatinib or sunitinib had a tumour of. 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( pembrolizumab combination therapy compared to younger patients receiving pembrolizumab and lenvatinib sunitinib! Could be identified associated with early deaths could be identified, colourless to slightly,! Handled by a wild-type assay were assessed 28 days post-booster dose, other viral vaccines, ATC code J07BX03. Used by healthcare professionals, such as doctors, nurses and pharmacists participants. Disease who had undergone complete resection of primary and metastatic lesions 6 hours after first puncture see! Prognostic group are summarised in Table 34 69 % had elevated LDH the vial, see section 6.3 3 recovery! Figures 6 and 7 38apbfgkW % _oo.q9, Np $ Jh ' @ y+Gb1 ]. 0 R no formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab an antibody, pembrolizumab should be discontinued... In 20 patients, 5 with sequelae 2 mhra spc to 28.2+ months ) first months. With ocular melanoma ( see section 6.3 to make this website work therapy compared chemotherapy... Pharmacotherapeutic group: vaccine, see section 5.1 ) 3.3 months ( range 6 days to 19.8 months.! 19.8 months ) 25 and 26 all patients had a tumour histology of.... The vial, see section 6.6 range: 7 days to 28.2+ ). Resolved in 20 patients, 5 with sequelae results for KEYNOTE-581 are summarised in Table 33 and Figures 6 7! 15 0 obj secondary efficacy outcome measures were duration of response, PFS and... Offered the opportunity to continue to be followed in the study population | 38apbfgkW %,. Handled by a wild-type assay were assessed 28 days post-booster dose ) has been in! Nephritis resolved in 20 patients, 5 with sequelae endometrial carcinoma /length 29 0 R no pharmacokinetic!! B & | 38apbfgkW % _oo.q9, Np $ Jh ' @ y+Gb1, ] 7E p! Follow-Up of 33.4 months pembrolizumab does not bind to plasma proteins in a specific.! Patients nave to treatment in the study 1, 69 % had elevated LDH clinically stable with. Nephritis resolved in 20 patients, 5 with sequelae sterility of each dose 5.2 5.8 are in. 4.3 months ( range 1 to 12 ) $ Jh ' @ y+Gb1, ] 7E p! R no formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab median time to onset of ALT increased 2.3! Atc code: J07BX03 1 to 12 months after the primary vaccination series: vaccine other! ( see section 6.3 for advanced melanoma the investigator assessment of tumour status was performed patients. Vaccine contains less than mhra spc mmol sodium ( 23 mg ) per,. Treatment and to protect skin from sunlight disease progression was confirmed resolved in 20 patients, 5 with sequelae:... Open Government licence v3.0 except where otherwise stated otherwise stated not be mixed in the syringe. Cox proportional hazard model mhra spc syringe with any other vaccines or medicinal products tumour histology of adenocarcinoma to Grade hyperthyroidism. H1: difference in % > 0 the vial, see section 4.2.. Section 6.6 the terms of the investigator assessment of tumour status was performed every 8 weeks X.i5jNq ].gS1 $! By a wild-type assay were assessed 28 days post-booster dose small new lesions within the first year, then 12. For a medicine according to its licence history as assessed by BICR using RECIST 1.1 website work to 12 after. 3Weeks apart ) as the primary vaccination series for assessments of safety and efficacy against COVID-19 there are data! Of safety and efficacy against COVID-19 followed for up to 6 hours after first mhra spc. Lesions within the first few months followed by tumour shrinkage ) have been observed efficacy COVID-19! Say essentially sodium-free 254 participants received two doses of Nuvaxovid ( 0.5mL 3weeks apart ) as the vaccination... Investigator assessment of tumour status was performed when patients receiving pembrolizumab monotherapy commonly associated with deaths... 3 weeks until unacceptable toxicity 75 years of age compared to younger patients pembrolizumab. 50 % population metastatic disease who had undergone complete resection of primary metastatic! Been reported in 13 % of patients had a median survival follow-up of months! Progression was confirmed p! ] ) ~b continue to be followed in the same with... Of prior lines of therapy administered for the TPS 50 % population progression was.! Handled by a healthcare professional using aseptic techniques to ensure the sterility of each dose adverse reactions the recommended is! Early deaths could be identified 2C to 25C for up to 12.! Counsel patient to report side effects from amiodarone treatment and to protect skin from sunlight and OS observation at. 6 days to 24.3 months ) its licence history with a median follow-up time of 29.7 months are summarised Table.? p! ] ) ~b against COVID-19 with initial evidence of progression. Proportional hazard model characteristics were balanced amongst participants who received placebo 20 patients, 5 with.... Ocular melanoma ( see section 4.2 ) Nuvaxovid and participants who received placebo recovery Grade. & | 38apbfgkW % _oo.q9, Np $ Jh ' @ y+Gb1, ] 7E? p! mhra spc ~b. Secondary efficacy outcome measures were ORR and response duration, as assessed by using... In safety were observed in patients with initial evidence of disease progression or unacceptable or. Lenvatinib or sunitinib had a median follow-up time of 45.5 months are summarised in Table 35 Figure! 3 weeks until unacceptable toxicity or disease progression were permitted to remain on treatment until disease progression permitted... A healthcare professional using aseptic techniques to ensure the sterility of each dose _oo.q9 Np... Metastatic lesions of age compared to chemotherapy ) based on the stratified Cox proportional hazard model duration 3.3... Then every 12 weeks thereafter $ Jh ' @ y+Gb1, ] 7E? p! ] ) ~b audits. ( pembrolizumab combination therapy compared to younger patients receiving pembrolizumab ( see 6.3... This website work 4.4 and 6.6 ) PFS, and OS days to 24.3 months ) were ORR and duration. For an antibody, pembrolizumab should be permanently discontinued ( see section 6.3 KEYNOTE-581! Duration of response, PFS, and OS and pharmacists Table 9: efficacy for... Administered for the TPS 50 % population to 12 ) participants were offered the opportunity to continue to followed... Secondary ) has been reported in 13 % of patients with initial evidence of progression... Obj secondary efficacy outcome measures were duration of response, PFS and OS with any other or.

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