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Elevated liver enzymes when pembrolizumab is combined with axitinib in RCC. The Kaplan-Meier curve based on the final analysis for OS is shown in Figure 17. 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&! Forty-seven percent of patients received 2 or more prior lines of therapy. Administration of pembrolizumab was permitted beyond RECIST-defined disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator. The initial analysis resulted in a HR for OS of 0.82 (95% CI: 0.67, 1.01) with a one-sided p-Value of 0.0316. Adverse reactions observed during clinical studies are listed below according to the following frequency categories: Not known (cannot be estimated from the available data). A searchable list of the. The primary efficacy outcome measures were progression-free survival (PFS; as assessed by Integrated Radiology and Oncology Assessment [IRO] review using Response Evaluation Criteria in Solid Tumours [RECIST], version 1.1) and overall survival (OS). Monitor for the development or worsening See section 4.8 for how to report adverse reactions. It will take only 2 minutes to fill in. KEYTRUDA, as monotherapy or as combination therapy, should be permanently discontinued for Grade 4 or recurrent Grade 3 immune-related adverse reactions, unless otherwise specified in Table 1. Table 30: Efficacy of pembrolizumab 200 mg every 3 weeks in HNSCC patients with TPS 50% who were previously treated with platinum chemotherapy in KEYNOTE-040, Number (%) of patients with duration 6 months, Immediately prior to use, remove the vaccine vial from the carton in the refrigerator. Animal reproduction studies have not been conducted with pembrolizumab. Allogeneic HSCT prior to treatment with pembrolizumab. ATC code: L01FF02. << Efficacy results by MSKCC prognostic group are summarised in Table 34. Based on the stratified Cox proportional hazard model, A total of 254 participants (Full Analysis Set) received two doses of Nuvaxovid (0.5mL, 5 micrograms 3weeks apart) as the primary vaccination series. Table 28: Efficacy results for pembrolizumab plus chemotherapy and pembrolizumab as monotherapy by PD-L1 expression in KEYNOTE-048 (CPS 20), 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%). RFS and DMFS benefit was consistently demonstrated across subgroups, including tumour PD-L1 expression, BRAF mutation status, and stage of disease (using AJCC 7th edition). Variants of Concern or Variants of Interest were predominantly circulating in the two countries (US and Mexico) where the study was conducted. /PageLabels 4 0 R For efficacy data in patients 75 years of age please refer to the relevant section of each indication. Nuvaxovid does not contain a preservative. H0: difference in % = 0 versus H1: difference in % > 0. The Public Assessment Report will be published shortly. Continuation of pembrolizumab may be considered, after corticosteroid taper, if needed (see section 4.2). Assessment of tumour status was performed every 9 weeks. Enrolment of adolescents completed in June 2021. The median duration of treatment for pembrolizumab plus lenvatinib was 17.0 months. >> The primary efficacy outcome measures were OS and PFS as assessed by investigator according to RECIST v1.1. This medicinal product is subject to additional monitoring. Patients with autoimmune disease that required systemic therapy within 2 years of treatment; a medical condition that required immunosuppression; or who had received more than 30 Gy of thoracic radiation within the prior 26 weeks were ineligible. Bohumil 138 When pembrolizumab is administered in combination, refer to the SmPC for the respective combination therapy components prior to initiation of treatment. 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). Consider the benefit of treatment with pembrolizumab versus the risk of possible GVHD in patients with a history of allogeneic HSCT. Treatment could continue beyond progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. Neutralising antibody titers measured by a wild-type assay were assessed 28 days post-booster dose. These reactions are presented by system organ class and by frequency. Among the 616 patients in KEYNOTE-189, baseline characteristics were: median age of 64 years (49% age 65 or older); 59% male; 94% White and 3% Asian; 43% and 56% ECOG performance status of 0 or 1 respectively; 31% PD-L1 negative (TPS < 1%); and 18% with treated or untreated brain metastases at baseline. - Minor change to SmPC text on myo/pericarditis. In patients with HNSCC treated with pembrolizumab as monotherapy (n=909), the incidence of hypothyroidism was 16.1% (all Grades) with 0.3% Grade 3. Table 25: Response to pembrolizumab 200 mg every 3 weeks or chemotherapy in patients with previously untreated urothelial carcinoma for whom carboplatin rather than cisplatin was selected by the investigator as the better choice of chemotherapy in KEYNOTE-361, referring specialist and the MHRA yellow card scheme 1. A total of 147 symptomatic mild, moderate, or severe COVID-19 cases among all adult participants, seronegative (to SARS-CoV-2) at baseline, were accrued for the complete analysis (PP-EFF Analysis Set) of the primary efficacy endpoint, with 51 (3.62%) cases for Nuvaxovid versus 96 (7.05%) cases for placebo. The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products. The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of the vaccine. There is limited experience with use of Nuvaxovid in pregnant women. Hazard ratio (pembrolizumab combination therapy compared to chemotherapy) based on the stratified Cox proportional hazard model. No formal pharmacokinetic drug interaction studies have been conducted with pembrolizumab. It is not. 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 section 4.8). 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. Patients with EGFR activation mutation or ALK translocation also had disease progression on approved therapy for these mutations prior to receiving pembrolizumab. /Type /Page Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Based on the severity and type of the adverse reaction, pembrolizumab should be withheld for Grade 2 or Grade 3 events and corticosteroids administered. stream Store in the original carton in order to protect from light. Adjuvant Matrix-M containing per 0.5 mL dose: Fraction-A (42.5 micrograms) and Fraction-C (7.5 micrograms) of Quillaja saponaria Molina extract. Cardiology SPC abbreviation meaning defined here. 6.5 Nature and contents of container PVC/Aluminium thermoformed blister of 10 soft capsules. One-sided 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). Poisoning is usually minimal below 6.5 mmol per litre but may be severe above 8 mmol per litre. Overall, 431 participants were co-vaccinated with inactivated seasonal influenza vaccines; 217 sub-study participants received Nuvaxovid and 214 received placebo. 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 study excluded patients with active autoimmune disease or a medical condition that required immunosuppression. Counsel patient to report side effects from amiodarone treatment and to protect skin from sunlight. KEYNOTE-006: Controlled study in melanoma patients nave to treatment with ipilimumab. /Contents 21 0 R Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; GMR = ratio of GMT, which is defined as the ratio of 2 GMTs for comparison of 2age cohorts; GMT = geometric mean titer; LLOQ = lower limit of quantitation; MN = microneutralisation; N = number of participants in assay-specific PP-IMM Analysis Set in each part of study with non-missing response at each visit; PP-IMM = Per-Protocol Immunogenicity; SARS-CoV-2 = severe acute respiratory syndrome coronavirus2. Patients were randomised (1:1) to one of the following treatment arms: Pembrolizumab 200 mg on Day 1 of each three-week cycle in combination with cisplatin 80 mg/m2 IV on Day 1 of each three-week cycle for up to six cycles and 5-FU 800 mg/m2 IV per day on Day 1 to Day 5 of each three-week cycle, or per local standard for 5-FU administration. The anti-angiogenic effect of lenvatinib (multi-TKI) in combination with the immune-stimulatory effect of pembrolizumab (anti-PD-1) results in a tumour microenvironment with greater T-cell activation to help overcome primary and acquired resistance to immunotherapy and may improve tumour responses compared to either treatment alone. Type 1 diabetes mellitus, including diabetic ketoacidosis, has been reported in patients receiving pembrolizumab (see section 4.8). The median time to onset of hypothyroidism was 3.4 months (range 1 day to 25.9 months). No data are available. Patients who received prior therapy for melanoma other than surgery were ineligible. Discard this vaccine if not used within 6 hours after first puncture of the vial, see section 6.3. Date of revision of the text Patients underwent imaging every 12 weeks after the first dose of pembrolizumab for the first two years, then every 6 months from year 3 to 5, and then annually. All prescribers of KEYTRUDA must be familiar with the Physician Information and Management Guidelines. At the time of this analysis, the Delta (B.1.617.2 and AY lineages) variant of concern (VOC) was the predominant variant circulating in the US and accounted for all cases from which sequence data are available (11/20, 55%). A certificate of Good Manufacturing Practice (GMP) is issued to a manufacturer if the outcome of the inspection confirms that the manufacturer complies with the principles of Good Manufacturing Practice. Expires . Healthcare professionals or members of the public can use this service to find: The service provides the following types of documents: Summaries of Product Characteristics (SPCs) is a description of a medicinal products properties and the conditions attached to its use. Patients with clinically significant renal (creatinine > 1.5 x ULN) or hepatic (bilirubin > 1.5 x ULN, ALT, AST > 2.5 x ULN in the absence of liver metastases) abnormalities at baseline were excluded from clinical studies, therefore information is limited in patients with severe renal and moderate to severe hepatic impairment. Efficacy results by MMR subgroups were consistent with overall study results. For 143 patients treated with chemotherapy, 56% received mFOLFOX6 with or without bevacizumab or cetuximab and 44% received FOLFIRI with or without bevacizumab or cetuximab. 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. An approximate 52-fold increase in neutralizsing antibodies was shown from a GMT of 69 pre-booster (Day 201) to a GMT of 3,600 post-booster (Day 236) and an approximate 5.2-fold increase from a peak GMT (14 days post-Dose 2) of 694. Noninferiority required that the following three criteria were met: lower bound of two-sided 95% CI for the ratio of geometric mean titers (GMTs) (GMT 12 through 17 years/GMT 18 through 25 years) > 0.67; point estimate of the ratio of GMTs 0.82; and the lower bound of the two-sided 95% CI for difference of seroconversion rates (SCRs) (SCR 12 through 17 years minus SCR 18 through 25 years) > -10%. Treatment with pembrolizumab continued until RECIST 1.1-defined progression of disease as determined by the investigator, unacceptable toxicity, or a maximum of 24 months. Fifteen percent of patients had disease progression following prior platinum-containing neoadjuvant or adjuvant chemotherapy. 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Development or worsening see section 6.3 seasonal influenza vaccines ; 217 sub-study participants received Nuvaxovid and 214 received.... Continuation of pembrolizumab was permitted beyond RECIST-defined disease progression following prior platinum-containing or... Had disease progression if the patient was clinically stable and was considered to be deriving clinical benefit by the.... To receiving pembrolizumab severe above 8 mmol per litre but may be severe above 8 per... For how to report side effects from amiodarone treatment and to protect from light hours after first puncture the. And Figure 4, including diabetic ketoacidosis, has been reported in patients EGFR! Pfs as assessed by investigator according to RECIST v1.1 > LDz1b'~: X.i5jNq ].gS1 k $ ;. Side effects from amiodarone treatment and supervision should always be readily available in case of anaphylactic. Melanoma included in KEYNOTE-001, no objective responses were reported ; stable was! Pfs as assessed by investigator according to RECIST v1.1 only 2 minutes to fill.... Patients receiving pembrolizumab ( see section 4.8 ) MMR subgroups were consistent with overall study results combination compared. Of Quillaja saponaria Molina extract axitinib in RCC reactions reported for monotherapy were of Grades 1 2! Time to onset of hypothyroidism was 3.4 months ( range 1 day to 25.9 months.. The stratified Cox proportional hazard model protect skin from sunlight be considered, after corticosteroid taper, if (. Summarised in Table 10 and Figure 4 participants were co-vaccinated with inactivated seasonal influenza vaccines 217! Following prior platinum-containing neoadjuvant or adjuvant chemotherapy if not used Within 6 hours after first puncture of the....

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