The MHRA products website allows you to find: You can look for any word, phrase or Product Licence number (PL) using the search tool. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Based on patients with a best objective response as confirmed complete or partial response. Please regularly check this information as it is often updated. The ORR difference (95% CI) for the favourable, intermediate and poor risk groups were 17.0% (5.3, 28.4), 25.5% (16.7, 33.9), and 31.5% (15.7, 46.2), respectively. Secondary efficacy outcome measures were ORR and response duration, as assessed by BICR using RECIST 1.1. KEYTRUDA as monotherapy is indicated for the treatment of the following MSI-H or dMMR tumours in adults with: - advanced or recurrent endometrial carcinoma, 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; - unresectable or metastatic gastric, small intestine, or biliary cancer, who have disease progression on or following at least one prior therapy. In this patient population, the median observation time was 8.5 months (range: 1 day to 39 months) and the most frequent adverse reactions with pembrolizumab were fatigue (31%), diarrhoea (22%), and nausea (20%). Pembrolizumab has not been studied in patients with severe hepatic impairment (see section 4.2). The primary efficacy outcome measure was OS. 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. /Title (Microsoft Word - 1646658070014998238_spc-doc.doc) It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. Randomisation was stratified by tumour PD-L1 expression (TPS < 1% [negative] vs. TPS 1%), investigator's choice of paclitaxel or nab-paclitaxel, and geographic region (East Asia vs. non-East Asia). /Contents 23 0 R A searchable list of the. Limited data are currently available on response duration following pembrolizumab discontinuation at cycle 35. The primary efficacy outcome measures were investigator-assessed RFS in the whole population and in the population with PD-L1 positive tumours, where RFS was defined as the time between the date of randomisation and the date of first recurrence (local, regional, or distant metastasis) or death, whichever occurs first. 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). Approval date: September 2019, updated December 2019 Review date: December 2021 (or earlier if indicated) South East London Area Prescribing Committee. Efficacy results for OS were consistent regardless of the age of tumour specimen (new vs. archival) based on an intergroup comparison. 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. << Alternatively, ALSA operates a bus from Malaga to Seville 4 times a day. KEYNOTE-052 also included patients eligible for mono-chemotherapy, for whom no randomised data are available. Patients with active, non-infectious pneumonitis, an allogeneic HSCT within the past 5 years (or > 5 years but with symptoms of GVHD), active autoimmune disease, a medical condition that required immunosuppression, or an active infection requiring systemic therapy were ineligible for the study. Date of revision of the text Some information may have been excluded from public view. * The primary analysis of PFS included censoring for new anti-cancer treatment. Seventy percent had at least two and 35% of patients had three or more prior systemic therapies for advanced melanoma. 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. The efficacy of pembrolizumab in combination with pemetrexed and platinum chemotherapy was investigated in a multicentre, randomised, active-controlled, double-blind study, KEYNOTE-189. Mix diluted solution by gentle inversion. Tickets cost 20 - 26 and the journey takes 1h 55m. *, The median time to onset of pneumonitis was 3.9 months (range 2 days to 27.2 months). /Filter /FlateDecode of the medications below as listed in their respective SPC Adults and children of less than 13 kg body weight 1 By exception, treatment outside the above "severe" criteria may be used in the context of treating children or to facilitate shortening the duration of infectiousness due to other complex medical needs. Response: Best objective response as confirmed complete response or partial response, Figure 38: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-826 patients with PD-L1 expression (CPS 1), * Chemotherapy (paclitaxel and cisplatin or paclitaxel and carboplatin) with or without bevacizumab, Figure 39: Kaplan-Meier curve for progression free survival by treatment arm in KEYNOTE-826 patients with PD-L1 expression (CPS 1). Monitor for the development or worsening 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. Pituitary function and hormone levels should be monitored to ensure appropriate hormone replacement. At the pre-specified interim analysis of ORR (median follow-up time of 12.8 months), statistically significant superiority was achieved for ORR comparing pembrolizumab plus axitinib with sunitinib p-Value < 0.0001. There are no data available on the interchangeability of Nuvaxovid with other COVID-19 vaccines to complete the primary vaccination course. The baseline characteristics of these 383 patients were: median age of 63 years (range: 28 to 89), 41% age 65 or older; 82% male; 34% White and 56% Asian; 43% and 57% had an ECOG performance status of 0 and 1, respectively. The presence of a minor infection and/or low-grade fever should not delay vaccination. Table 31 summarises key efficacy measures and Figures 23 and 24 show the Kaplan-Meier curves for OS and PFS based on the final analysis with a median follow-up time of 37.7 months. Cisplatin could be administered on Day 2 of each 3-week treatment cycle. Pembrolizumab has not been studied in patients with severe renal impairment (see section 4.2). Of the 617 enrolled patients, 548 patients (89%) had tumours expressing PD-L1with a CPS 1 based on the PD-L1 IHC 22C3 pharmDxTM Kit. The safety profile in paediatric patients was generally similar to that seen in adults treated with pembrolizumab. The Public Assessment Report will be published shortly. 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). Well send you a link to a feedback form. 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. Immediately prior to use, remove the vaccine vial from the carton in the refrigerator. These conditions can develop within just a few days after vaccination and have primarily occurred within 14 days. For storage conditions after first opening of the medicinal product, see section 6.3. All but one patient was white. Mild COVID-19 was defined as fever, new onset cough or at least 2 or more additional COVD-19 symptoms. 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). << 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. endobj Randomisation was stratified by risk categories (favourable versus intermediate versus poor) and geographic region (North America versus Western Europe versus Rest of the World). Patients were randomly assigned to receive pembrolizumab at a dose of 2 mg/kg bw every 3 weeks or 10 mg/kg bw every 3 weeks. Alnylam B.V. Netherlands has obtained approval from the MHRA to supply German product (batch number 650313; batch size 280 packs), which is expected to be on the UK market . Data from clinical trials in adolescent melanoma patients is very limited and extrapolation from adult data has been used to establish efficacy. - Update the SmPC and PIL to extend the indication for booster dose to the 12+ years age group (previously 18+ years) Patients were treated with pembrolizumab until unacceptable toxicity or disease progression. Hyperthyroidism resolved in 315 (79.9%) patients, 11 with sequelae. The primary efficacy outcome measures were OS and PFS as assessed by investigator according to RECIST v1.1. Since pembrolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected. 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). 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. /MediaBox [0 0 595 842] The efficacy of pembrolizumab was investigated in KEYNOTE-177, a multicentre, randomised, open-label, active-controlled study that enrolled patients with previously untreated metastatic MSI-H or dMMR CRC. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Efficacy results in this subpopulation were consistent with the ITT population. You have rejected additional cookies. 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. Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. Corticosteroid therapy may be considered. endobj Events of anaphylaxis have been reported with Nuvaxovid vaccines. QRjj$HUwg MSI or MMR (mismatch repair) tumour status was determined locally using polymerase chain reaction (PCR) or IHC, respectively. Participants with known stable infection with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV) were not excluded from enrolment. 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. BRAF mutations were reported in 13% of the study population. - Minor change to SmPC text on myo/pericarditis. Of the patients randomised to the chemotherapy arm, 55% crossed over and subsequently received treatment with pembrolizumab. 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