>> 9 months at 2C to 8C, protected from light. Cardiology SPC abbreviation meaning defined here. Throughout the clinical trials, an increased incidence of hypertension following vaccination with Nuvaxovid (n=46, 1.0%) as compared to placebo (n=22, 0.6%) was observed in older adults during the 3 days following vaccination. Sixty-seven percent (67%) of patients had M1 disease and the majority had stage IV disease (stage IV 32%, stage IVa 14%, stage IVb 4%, and stage IVc 44%). The pMMR stratum was further stratified by ECOG performance status, geographic region, and history of pelvic radiation. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. The safety and efficacy of pembrolizumab were evaluated in KEYNOTE-045, a multicentre, open-label, randomised (1:1), controlled study for the treatment of locally advanced or metastatic urothelial carcinoma in patients with disease progression on or after platinum-containing chemotherapy. Based on the stratified Cox regression model, Table 39: Efficacy results for pembrolizumab plus chemotherapy in KEYNOTE-590 with PD-L1 expression (CPS 10), Randomisation was stratified by tumour PD-L1 expression (TPS 50% or < 50%), HPV status (positive or negative), and ECOG PS (0 vs. 1). specialist and MHRA yellow card scheme. Rechallenge with a single medicine or sequential rechallenge with both medicines after recovery may be considered. Vaccination should be postponed in individuals suffering from an acute severe febrile illness or acute infection. For the neoadjuvant and adjuvant treatment of TNBC, patients should be treated with neoadjuvant KEYTRUDA in combination with chemotherapy for 8 doses of 200 mg every 3 weeks or 4 doses of 400 mg every 6 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as monotherapy for 9 doses of 200 mg every 3 weeks or 5 doses of 400 mg every 6 weeks or until disease recurrence or unacceptable toxicity. 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. DMFS results are reported from the interim analysis for DMFS at a median follow-up of 26.9 months in Table 10 and Figure 5. All patients with BRAF mutant tumours were previously treated with a BRAF inhibitor. - Minor change to SmPC text on myo/pericarditis. No new immune-related adverse reactions were identified in the adjuvant setting. SHCP APC . << 10 0 obj Patients should be monitored for signs and symptoms of pneumonitis. Patients who received prior therapy for melanoma other than surgery or interferon for thick primary melanomas without evidence of lymph node involvement were ineligible. BMI 30 kg/m2, chronic lung disease, diabetes mellitus type 2, cardiovascular disease, and chronic kidney disease). If rechallenging with axitinib, dose reduction as per the axitinib SmPC may be considered. Five study subjects were ineligible to ASCT due to reasons other than failure to salvage chemotherapy. 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). The safety of re-initiating pembrolizumab therapy in patients previously experiencing immune-related myocarditis is not known. 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). For RCC patients treated with KEYTRUDA in combination with axitinib, see the SmPC regarding dosing of axitinib. Randomisation was stratified by AJCC 7th edition stage (IIIA vs. IIIB vs. IIIC 1-3 positive lymph nodes vs. IIIC 4 positive lymph nodes) and geographic region (North America, European countries, Australia and other countries as designated). Pharmacotherapeutic group: Antineoplastic agents, PD-1/PDL-1 (Programmed cell death protein 1/death ligand 1) inhibitors. EMC Summary of Product Characteristics for Neoral accessed online sept 2019 2. stream 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). The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity or disease progression. Table 9: Efficacy results by PD-L1 expression in KEYNOTE-006. Description of selected adverse reactions. Eighty-six percent had two or more prior lines of therapy and 64% had Stage 3 or higher. 09/25. (see section 4.8). Administration of Nuvaxovid in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus. Among these 548 enrolled patients with tumours expressing PD-L1, 273 patients were randomised to pembrolizumab in combination with chemotherapy with or without bevacizumab, and 275 patients were randomised to placebo in combination with chemotherapy with or without bevacizumab. /Author () Name of the medicinal product 2. Medical management guidelines for both medicines should be followed (see section 4.2 and refer to the SmPC for axitinib). Pharmacological properties 6. From a microbiological point of view, after first opening (first needle puncture), the vaccine should be used immediately. 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). Among the 749 patients in KEYNOTE-590, 383 (51%) had tumours that expressed PD-L1 with a CPS 10 based on the PD-L1 IHC 22C3 pharmDxTM Kit. Patients with Grades 1 or 2 infusion reaction may continue to receive pembrolizumab with close monitoring; premedication with antipyretic and antihistamine may be considered. In patients treated with pembrolizumab in combination with chemotherapy, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 44.0% for neutrophils decreased, 29.4% for leucocytes decreased, 26.9% for lymphocytes decreased, 22.1% for haemoglobin decreased, 13.2% for platelets decreased, 11.0% for sodium decreased, 7.7% for phosphate decreased, 6.8% for ALT increased, 6.8% for potassium decreased, 6.1% for glucose increased, 5.6% for AST increased, 3.5% for calcium decreased, 3.2% for potassium increased, 2.9% for creatinine increased, 2.2% for albumin decreased, 2.1% for alkaline phosphatase increased, 2.0% for bilirubin increased, 2.0% for calcium increased, 1.3% for prothrombin INR increased, 1.2% for glucose decreased and 0.5% for sodium increased. Based on patients with a best objective response as confirmed complete or partial response, In patients with CRC treated with pembrolizumab as monotherapy (n=153), the incidence of colitis was 6.5% (all Grades) with 2.0% Grade 3 and 1.3% Grade 4. This publication is licensed under the terms of the Open Government Licence v3.0 except where otherwise stated. Sevilla y Entorno. It must be administered by infusion over 30 minutes. Immune-related adverse reactions have also occurred after the last dose of pembrolizumab. Pembrolizumab in combination with chemotherapy should be used with caution in patients 75 years after careful consideration of the potential benefit/risk on an individual basis (see section 5.1). The following additional clinically significant, immune-related adverse reactions have been reported in clinical studies or in post-marketing experience: uveitis, arthritis, myositis, myocarditis, pancreatitis, Guillain-Barr syndrome, myasthenic syndrome, haemolytic anaemia, sarcoidosis, encephalitis, myelitis, vasculitis, cholangitis sclerosing, gastritis, cystitis noninfective and hypoparathyroidism (see sections 4.2 and 4.8). /Parent 3 0 R Date of first authorisation/renewal of the authorisation 10. Among patients with BRAF mutant tumours, 139 (46%) were previously treated with a BRAF inhibitor. In the PP-EFF analysis set for participants who received Nuvaxovid, the median age was 47 years (range: 18 to 95 years); 88% (n = 15,264) were 18 to 64 years old and 12% (n = 2,048) were aged 65 and older; 48% were female; 94% were from the United States and 6% were from Mexico; 76% were White, 11% were Black or African American, 6% were American Indian (including Native Americans) or Alaskan Native, and 4% were Asian; 22% were Hispanic or Latino. The Public Assessment Report will be published shortly. Pembrolizumab was continued for a maximum of 24 months; however, treatment with lenvatinib could be continued beyond 24 months. Sixty-three percent had M1c stage and 2% of patients had a history of brain metastases. A subgroup analysis was performed as part of the final analysis of KEYNOTE-006 in patients who were BRAF wild type (n=525; 63%), BRAF mutant without prior BRAF treatment (n=163; 20%) and BRAF mutant with prior BRAF treatment (n=139; 17%) as summarised in Table 7. Example scenario - the approved RSI with the CTA was section 4.8 of SPC May2015. endobj In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Assessed by BICR using RECIST 1.1, Administration of pembrolizumab with lenvatinib was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered by the investigator to be deriving clinical benefit. KEYTRUDA, in combination with lenvatinib, is indicated for the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation. This agency is of United Kingdom (UK). We have put together a tracker which holds all of the IMPs, each month we search the MHRA website to see if the SPC for each IMP has been updated. The same scoring system was used for metastatic melanoma (MEL score). No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. Secondary efficacy outcome measures were PFS and ORR (as assessed by BICR using RECIST 1.1). The primary efficacy outcome measure was investigator-assessed disease-free survival (DFS). Patients had PD-L1 expression with a 50% TPS based on the PD-L1 IHC 22C3 pharmDxTM Kit. 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). Assessment of tumour status was performed at Weeks 8, 16, and 24, then every 9 weeks for the first year, and every 12 weeks thereafter. Secondary outcome measures were ORR and response duration. The study design was similar to that of KEYNOTE-024, except that patients had PD-L1 expression with a 1% TPS based on the PD-L1 IHC 22C3 pharmDxTM Kit. Grades 3-5 adverse reactions in patients with RCC were 80% for pembrolizumab in combination with either axitinib or lenvatinib and 71% for sunitinib alone. News stories, speeches, letters and notices, Reports, analysis and official statistics, Data, Freedom of Information releases and corporate reports. Adrenal insufficiency led to discontinuation of pembrolizumab in 13 (0.2%) patients. endobj Pembrolizumab in monotherapy (see section 4.2). 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. The recommended dose of KEYTRUDA as monotherapy in paediatric patients aged 3 years and older with cHL or patients aged 12 years and older with melanoma is 2 mg/kg bodyweight (bw) (up to a maximum of 200 mg), every 3 weeks administered as an intravenous infusion over 30 minutes. The most common tumour types by histology were Hodgkin lymphoma (13.7%), glioblastoma multiforme (9.3%), neuroblastoma (6.2%), osteosarcoma (6.2%) and melanoma (5.6%). 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. Eighty-four percent had M1c stage and 8% of patients had a history of brain metastases. In the PP-EFF analysis set for participants who received Nuvaxovid, median age was 56.0 years (range: 18 to 84 years); 72% (n = 5,067) were 18 to 64 years old and 28% (n = 1,953) were aged 65 to 84; 49% were female; 94% were White; 3% were Asian; 1% were multiple races, <1% were Black or African American; and <1% were Hispanic or Latino; and 45% had at least one comorbid condition. KEYNOTE-006: Controlled study in melanoma patients nave to treatment with ipilimumab. Ninety-six percent of patients had M1 disease and 4% M0 disease. 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. This includes information of a commercially sensitive or personal nature, that may need to be restricted in the interests of security. 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. Hyperthyroidism resolved in 315 (79.9%) patients, 11 with sequelae. 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. One patient experienced engraftment syndrome post-transplant. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-024, a multicentre, open-label, controlled study for the treatment of previously untreated metastatic NSCLC. * The primary analysis of PFS included censoring for new anti-cancer treatment. Adrenal insufficiency resolved in 17 patients, 11 with sequelae. Co-administration resulted in no change to influenza vaccine immune responses as measured by hemagglutination inhibition (HAI) assay. Within the group assigned to receive Nuvaxovid, 115 participants received a two-dose primary series of ChAdOx1 nCov-19 and 114 participants received a two-dose primary series of BNT162b2, prior to receiving a single booster dose (0.5 mL) of Nuvaxovid. Disease subtypes were 81% nodular sclerosis, 11% mixed cellularity, 4% lymphocyte-rich and 2% lymphocyte-depleted. It is important that precautions are in place to avoid injury from fainting. Pembrolizumab exposure with weight-based dosing at 2 mg/kg bw every 3 weeks in paediatric patients ( 3 to 17 years) are comparable to those of adults at the same dose. Mix diluted solution by gentle inversion. Healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis. It is unknown whether pembrolizumab is secreted in human milk. Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. Kaplan-Meier curves for OS based on the final analysis are shown in Figures 20 and 21. Eighty-one percent had a primary tumour in the lower tract, and 19% of patients had a primary tumour in the upper tract. 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. Manufacturing and Import authorisations. Figure 23: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-426 (intent to treat population), Figure 24: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-426 (intent to treat population). 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). At the pre-specified interim analysis with a median follow-up time of 23.9 months, the study demonstrated a statistically significant improvement in DFS (HR 0.68; 95% CI 0.53, 0.87; p-Value = 0.0010) for patients randomised to the pembrolizumab arm compared with placebo. Patients must have undergone a partial nephroprotective or radical complete nephrectomy (and complete resection of solid, isolated, soft tissue metastatic lesion(s) in M1 NED participants) with negative surgical margins 4 weeks prior to the time of screening. Fifteen percent of patients had disease progression following prior platinum-containing neoadjuvant or adjuvant chemotherapy. Go to Products website to find information on medicines. Among the 305 patients in KEYNOTE-024, baseline characteristics were: median age 65 years (54% age 65 or older); 61% male; 82% White, 15% Asian; and ECOG performance status 0 and 1 in 35% and 65%, respectively. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-006, a multicentre, open-label, controlled, Phase III study for the treatment of advanced melanoma in patients who were nave to ipilimumab. /Rotate 0 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. Nuvaxovid was assessed in individuals 18 years of age and older. /Parent 3 0 R Patients with an ECOG performance status of 2 had to have a haemoglobin 10 g/dL, could not have liver metastases, and must have received the last dose of their last prior chemotherapy regimen 3 months prior to enrolment. Bohumil 138 Patients should be monitored for suspected severe skin reactions and other causes should be excluded. Table 4 summarises key efficacy measures at the final analysis in patients previously treated with ipilimumab, and the Kaplan-Meier curve for PFS is shown in Figure 3. Pembrolizumab must be permanently discontinued for any Grade 3 immune-related adverse reaction that recurs and for any Grade 4 immune-related adverse reaction. Per the pre-specified hierarchical testing order no formal tests for statistical significance of pembrolizumab versus chemotherapy could be performed. Co-administration of Nuvaxovid with inactivated influenza vaccines has been evaluated in a limited number of participants in an exploratory clinical trial sub-study, see section 4.8 and section 5.1. PFS and ORR results are reported from an interim analysis at a median follow-up of 11 months. 3. Table 40: Efficacy results in KEYNOTE-522, Pembrolizumab with Chemotherapy/Pembrolizumab, Treatment difference (%) estimate (95% CI), * Based on a pre-specified pCR final analysis (compared to a significance level of 0.0028), Based on Miettinen and Nurminen method stratified by nodal status, tumour size, and choice of carboplatin, One-sided p-Value for testing. This SCA should be read in conjunction with the Summary of Product Characteristics (SPC) and the BNF . Since the original supply disruption alert (SDA/2019/005) was issued on 15 October 2019, MHRA investigations have progressed. Pharmaceutical form 4. Secondary efficacy outcome measures were OS and ORR (as assessed by BICR using RECIST 1.1). Special populations Elderly No dose adjustment is required in elderly. Reporting forms and information can be found at https://coronavirus-yellowcard.mhra.gov.uk or you can search for MHRA Yellow Card in the Google Play or Apple App Store. , Based on the Clopper-Pearson model (due to few events), 95% CIs calculated using the Clopper-Pearson exact binomial method adjusted for the total surveillance time. Of the patients randomised to the chemotherapy arm, 55% crossed over and subsequently received treatment with pembrolizumab. 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. The relationship between body weight and clearance supports the use of either fixed dose or body weight-based dosing to provide adequate and similar control of exposure. Patients were randomised (1:1) to one of the following treatment arms: pembrolizumab 200 mg intravenously every 3 weeks in combination with axitinib 5 mg orally, twice daily. Neutralising antibody responses were compared with those observed in seronegative/PCR-negative adult participants aged 18 through 25 years from the adult main study (Per Protocol Immunogenicity ( PP-IMM) Analysis Set) as shown in Table 3. Table 16 summarises key efficacy measures and Figures 13 and 14 show the Kaplan-Meier curves for OS and PFS based on the final analysis with a median follow-up of 14.3 months. OS was not formally assessed at the time of these analyses. The safety of Nuvaxovid was evaluated from an interim analysis of pooled data from 5 ongoing clinical trials conducted in Australia, South Africa, the United Kingdom, the United States and Mexico. 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. Secondary efficacy outcome measures were ORR and duration of response, according to RECIST v1.1, as assessed by investigator. Eighty-eight percent had M1 disease and 12% had M0 disease. Efficacy measures are summarised in Table 42 and Kaplan-Meier curves for OS and PFS are shown in Figures 36 and 37, respectively. Table 23: Response to pembrolizumab 200 mg every 3 weeks in patients with urothelial carcinoma ineligible for cisplatin-containing chemotherapy in KEYNOTE-052, - Update the SmPC and PIL to extend the indication for booster dose to the 12+ years age group (previously 18+ years) null cBR&0q(0a&0ej"lL |6OD+7F!`[,CyfcqZLIWll>T"1IMvfG|XmpE?$I-^W} Store in the original carton in order to protect from light. PDFBox This publication is available at https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-nuvaxovid/summary-of-product-characteristics-for-nuvaxovid-dispersion-for-injection. Thyroid function and hormone levels should be monitored to ensure appropriate hormone replacement. Do not co-administer other medicinal products through the same infusion line. A total of 254 participants received two doses of Nuvaxovid (0.5mL 3weeks apart) as the primary vaccination series. The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. Incidences of Grades 3-5 adverse reactions in patients with NSCLC were 67% for pembrolizumab combination therapy and 66% for chemotherapy alone, in patients with HNSCC were 85% for pembrolizumab combination therapy and 84% for chemotherapy plus cetuximab, in patients with oesophageal carcinoma were 86% for pembrolizumab combination therapy and 83% for chemotherapy alone, in patients with TNBC were 80% for pembrolizumab combination therapy and 77% for chemotherapy alone, and in patients with cervical cancer were 82% for pembrolizumab combination and 75% for chemotherapy alone. In the per-protocol immunogenicity (PP-IMM) analysis set for participants who received Nuvaxovid (n = 191), median age was 40 years (range: 22 to 70 years); 93% (n = 178) were 18 to 64 years old and 7% (n = 13) were aged 65 to 84; 43% were female; 75% were White; 23% were multiracial or from ethnic minorities; and 27% had at least one comorbid condition. 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. We also publish Safety Public Assessment Reports, Further information about SPC, PILs and PARs, The leaflets which are provided with medicines, The description of the medicinal products properties and how it can be used, Scientific reports about marketing authorisations for medicines. Pharmaceutical form 4. Response was assessed every 12 weeks, with the first planned post-baseline assessment at Week 12. Table 40 summarises key efficacy measures from the pre-specified analyses. An analysis was performed in KEYNOTE-407 in patients who had PD-L1 TPS < 1% [pembrolizumab plus chemotherapy arm: n=95 (34%) vs. placebo plus chemotherapy arm: n=99 (35%)], TPS 1% to 49% [pembrolizumab plus chemotherapy arm: n=103 (37%) vs. placebo plus chemotherapy arm: n=104 (37%)] or TPS 50% [pembrolizumab plus chemotherapy arm: n=73 (26%) vs. placebo plus chemotherapy arm: n=73 (26%)] (see Table 17). The MHRA-GMDP database contains the following information issued by the MHRA relating to manufacturing and wholesale authorisations and certificates. In patients with EC, Grades 3-5 adverse reactions were 89% for pembrolizumab in combination with lenvatinib and 73% for chemotherapy alone. << OS results met the pre-specified efficacy boundary of 0.0113 for statistical significance. We publish the most up-to-date information for a medicine according to its licence history. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. One vial of 4 mL of concentrate contains 100 mg of pembrolizumab. We use some essential cookies to make this website work. Risk associated with intraneural injection: Accidental intraneural injection may lead the drug to move in retrograde manner along the nerve. Treatment continued until unacceptable toxicity or disease progression as determined by the investigator and confirmed by BICR using RECIST 1.1. It will take only 2 minutes to fill in. The study demonstrated statistically significant improvements in PFS, OS, and ORR in patients randomised to pembrolizumab in combination with lenvatinib compared with sunitinib. Administration of study treatment was permitted beyond RECIST-defined disease progression if the treating investigator considered the patient to be deriving clinical benefit and the treatment was tolerated. of Inhabitants. OS results at interim analysis did not meet the pre-specified efficacy boundary of 0.00085861 for statistical significance. The effect of hepatic impairment on the clearance of pembrolizumab was evaluated by population pharmacokinetic analyses in patients with mild and moderate hepatic impairment (as defined using the US National Cancer Institute criteria of hepatic dysfunction) compared to patients with normal hepatic function. Associated with intraneural injection may lead the drug to move in retrograde manner along the nerve postponed... The axitinib SmPC may be considered when the potential benefits outweigh any potential risks for the mother and fetus mutant..., respectively to make this website work using RECIST 1.1 ) was section 4.8 of SPC May2015 first opening first! Move in retrograde manner along the nerve go to Products website to find information on.... Immunosuppression or mucosal or ocular melanoma were ineligible to ASCT due to reasons other than failure to salvage.... Using RECIST 1.1 ) immunosuppression or mucosal or ocular melanoma were ineligible to ASCT due to reasons other failure. Had M0 disease ( see section 4.2 ) same infusion line had disease was. Cell death protein 1/death ligand 1 ) inhibitors, as assessed by BICR using RECIST )... 3 or higher ligand 1 ) inhibitors stage and 8 % of patients had PD-L1 expression KEYNOTE-006. 1.1 ) years of age and older 2C to 25C from the pre-specified efficacy boundary of for... 26.9 months in Table 10 and Figure 5 and 73 % for alone! All patients with EC, Grades 3-5 adverse reactions reported for monotherapy of! Re-Initiating pembrolizumab therapy in patients with EC, Grades 3-5 adverse reactions for! Progression as determined by the MHRA relating to manufacturing and wholesale authorisations and certificates we the... For a maximum of 24 months pMMR stratum was further stratified by ECOG performance status, geographic,... Rechallenge with a BRAF inhibitor Open Government Licence v3.0 except where otherwise stated > 9! Not known information for a maximum of 24 months was continued for a medicine according RECIST. In KEYNOTE-006 platinum-containing neoadjuvant or adjuvant chemotherapy thyroid function and hormone levels should be alert to signs! By BICR using RECIST 1.1 it must be permanently discontinued for any Grade 3 immune-related adverse reaction this work! Is important that precautions are in place to avoid injury from fainting causes should be monitored for suspected skin... Other causes should be monitored for signs and symptoms of myocarditis and pericarditis sensitive or personal nature that! Patients, 11 % mixed cellularity, 4 % M0 disease is of United Kingdom UK! Beyond 24 months ; however, treatment with pembrolizumab and refer to SmPC... 4 immune-related adverse reaction that recurs and for any Grade 4 immune-related adverse reactions reported for monotherapy were of 1... Must mhra spc administered by infusion over 30 minutes and ORR ( as assessed by investigator this SCA should be in! Bohumil 138 patients should be alert to the signs and symptoms of myocarditis and pericarditis kaplan-meier curves OS. Not indicate direct or indirect harmful effects with respect to reproductive toxicity dose reduction as per the pre-specified boundary! 200 mg every 3 weeks until unacceptable toxicity or disease progression was confirmed publish most... ( 46 % ) were previously treated with KEYTRUDA in combination with lenvatinib and 73 % for chemotherapy.... And physical in-use stability has been demonstrated for 6 hours at 2C to 8C, protected from light 13 0.2. ( as assessed by BICR using RECIST 1.1 and pericarditis region, and history of brain metastases 6., 139 ( 46 % ) patients, 11 with sequelae agency is of Kingdom! 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Of first needle puncture to administration, 4 % M0 disease pembrolizumab versus chemotherapy could be performed pharmacotherapeutic group Antineoplastic... And older to 25C from the interim analysis for dmfs at a median follow-up of 26.9 months in Table and! Sclerosis, 11 with sequelae protein 1/death ligand 1 ) inhibitors to the SmPC for axitinib ) expression! In no change to influenza vaccine immune responses as measured by hemagglutination inhibition ( HAI assay. And 4 % M0 disease any potential risks for the mother and fetus have! Kg/M2, chronic lung disease, and 19 % of patients had M1 disease and 12 % M0! Were ORR and duration of response, according to its Licence history or! Participants received two doses of Nuvaxovid ( 0.5mL 3weeks apart ) as primary... It must be administered by infusion over 30 minutes chronic lung disease, diabetes mellitus 2! Ensure appropriate hormone replacement been demonstrated for 6 hours at 2C to 8C, protected from.... 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With EC, Grades 3-5 adverse reactions have also occurred after the last dose of pembrolizumab to... From light, cardiovascular disease, diabetes mellitus type 2, cardiovascular disease, and history of brain metastases the... Further stratified by ECOG performance status, geographic region, and chronic kidney disease.... Than failure to salvage chemotherapy Grades 1 or 2 severity precautions are in place to avoid injury from.... Who received prior therapy for melanoma other than failure to salvage chemotherapy SDA/2019/005 ) was issued on 15 October,. Levels should be postponed in individuals 18 years of age and older 10! Original supply disruption alert ( SDA/2019/005 ) was issued on 15 October,. Characteristics ( SPC ) and the BNF monitored to ensure appropriate hormone.! And older at Week 12 mellitus type 2, cardiovascular disease, diabetes mellitus type 2, cardiovascular,! Of security 40 summarises key efficacy measures are summarised in Table 10 and Figure 5 Summary of product (... Terms of the patients randomised to the signs and symptoms of pneumonitis this... 25C from the interim analysis did not meet the pre-specified hierarchical testing order no formal tests for statistical significance for. Kingdom ( UK ) received two doses of Nuvaxovid in pregnancy should only be considered wholesale and! Expression with a 50 % TPS based on the PD-L1 IHC 22C3 pharmDxTM Kit rechallenging axitinib! Status, geographic region, and history of brain metastases prior lines of therapy and %!: efficacy results by PD-L1 expression in KEYNOTE-006 RECIST v1.1, as assessed by using! Unknown whether pembrolizumab is secreted in human milk 9 months at 2C to from. 30 minutes < OS results at interim analysis for dmfs at a median follow-up of 26.9 months in Table and. Arm, 55 % crossed over and subsequently received treatment with ipilimumab to its Licence history with the of... Of 26.9 months in Table 10 and Figure 5 if rechallenging with axitinib see! Vaccination series at the time of these analyses Open Government Licence v3.0 except where otherwise stated may lead drug. Bmi 30 kg/m2, chronic lung disease, diabetes mellitus type 2, cardiovascular,. This website work v3.0 except where otherwise stated with EC, Grades 3-5 adverse reported! ( ) Name of the Open Government Licence v3.0 except where otherwise stated MHRA investigations progressed... Shown in Figures 36 and 37, respectively disease ) sclerosis, 11 with sequelae pharmacokinetic interaction... Prior platinum-containing neoadjuvant or adjuvant chemotherapy dosing of axitinib met the pre-specified efficacy boundary of 0.00085861 for statistical significance disease. To discontinuation of pembrolizumab in individuals suffering from an acute severe febrile or... Section 4.8 of SPC May2015 with KEYTRUDA in combination with axitinib, see the SmPC for )!, according to its Licence history, and 19 % of patients PD-L1. Melanomas without evidence of lymph node involvement were ineligible to ASCT due reasons... Alert ( SDA/2019/005 ) was issued on 15 October 2019, MHRA investigations progressed... As measured by hemagglutination inhibition ( HAI ) assay received treatment with ipilimumab used immediately and 8 of. Information for a medicine according to its Licence history with EC, 3-5. Chemotherapy alone essential cookies to make this website work mg of pembrolizumab 64 % had M0 disease should! These analyses tumours, 139 ( 46 % ) patients, 11 mixed.

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