Patients with active autoimmune disease, a medical condition that required immunosuppression, or known HER-2 positive GEJ adenocarcinoma patients were ineligible for the study. The median time to onset of severe skin reactions was 3.0 months (range 2 days to 25.5 months). Expires . The guidance, prepared by the Agency's SmPC Advisory Group, outlines the principles in the European Commission's guideline on SmPC. endobj Secondary efficacy outcome measures were ORR and duration of response, according to RECIST 1.1 as assessed by the investigator. Email Address: Registration No: KEYNOTE-052: Open-label study in urothelial carcinoma patients ineligible for cisplatin-containing chemotherapy. Kaplan-Meier curves for OS and PFS based on the final analysis are shown in Figures 1 and 2. myositis (myalgia, myopathy, necrotising myositis, polymyalgia rheumatica and rhabdomyolysis), dd. Tourist area. Among the 1,274 patients in KEYNOTE-042, 599 (47%) had tumours that expressed PD-L1 with TPS 50% based on the PD-L1 IHC 22C3 pharmDxTM Kit. H0: difference in % = 0 versus H1: difference in % > 0. KEYTRUDA is for single use only. Counsel patient to report side effects from amiodarone treatment and to protect skin from sunlight. /MediaBox [0 0 595 842] 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 . It allows continued monitoring of the benefit/risk balance of the medicinal product. Colitis resolved in 130 patients, 2 with sequelae. Patients should be monitored for suspected severe skin reactions and other causes should be excluded. 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. Use of pembrolizumab in urothelial carcinoma patients who have received prior platinum-containing chemotherapy. Sevilla y Entorno. A subgroup analysis was performed as part of the final analysis of KEYNOTE-002 in patients who were BRAF wild type (n=414; 77%) or BRAF mutant with prior BRAF treatment (n=126; 23%) as summarised in Table 6. Pharmaceutical particulars 7. The primary efficacy outcome measure was PFS based on BICR using RECIST 1.1. Table 13 summarises key efficacy measures for the TPS 50% population at the final analysis performed at a median follow-up of 15.4 months. Following administration of pembrolizumab 200 mg every 3 weeks in patients with cHL, the observed median Cmin at steady-state was up to 40% higher than that in other tumour types treated with the same dosage; however, the range of trough concentrations is similar. /Rotate 0 The licensing authority has deferred the obligation to submit the results of studies with Nuvaxovid in one or more subsets of the paediatric population in prevention of COVID-19, see section 4.2 for information on paediatric use. Qualitative and quantitative composition 3. 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. 9 months at 2C to 8C, protected from light. The use of this vaccine should be in accordance with official recommendations. In urothelial carcinoma, a higher number of deaths within 2 months was observed in pembrolizumab compared to chemotherapy (see section 5.1). Updated efficacy results with a median follow-up time of 45.5 months are summarised in Table 11 and Figures 6 and 7. Dose delay or discontinuation (see also section 4.4). 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). Lenvatinib should be withheld, dose reduced, or discontinued in accordance with the instructions in the lenvatinib SmPC for combination with pembrolizumab. Eighty-six percent had a primary tumour in the lower tract and 14% had a primary tumour in the upper tract. The primary efficacy outcome measures were PFS assessed by BICR according to RECIST v1.1 and OS. Following collection of a 60 days safety follow-up period, initial adolescent recipients of placebo were invited to receive two injections of Nuvaxovid 21days apart and initial recipients of Nuvaxovid to receive two injections of placebo 21days apart (blinded crossover). Ninety-seven percent of the patients had M1 disease and 3% had M0 disease (locally advanced unresectable). It is important that precautions are in place to avoid injury from fainting. 4 0 obj Table 14 summarises key efficacy measures and Figures 11 and 12 show the Kaplan-Meier curves for OS and PFS based on the final analysis with a median follow-up of 18.8 months. Patients with EGFR activation mutation or ALK translocation also had disease progression on approved therapy for these mutations prior to receiving pembrolizumab. Nephritis has been reported in patients receiving pembrolizumab (see section 4.8). << All patients with BRAF mutant tumours were previously treated with a BRAF inhibitor. Table 18: Response to pembrolizumab 2 or 10 mg/kg bw every 3 weeks in previously treated patients with NSCLC in KEYNOTE-010, * Hazard ratio (pembrolizumab compared to docetaxel) based on the stratified Cox proportional hazard model, Common sites of metastases in patients were lung (69%), lymph node (46%), and bone (26%). The dispersion is colourless to slightly yellow, clear to mildly opalescent (pH 7.2). An exploratory subgroup analysis was performed in KEYNOTE-048 in patients whose tumours expressed PD-L1 CPS 1 to < 20 [pembrolizumab plus chemotherapy: n=116 (45%) vs. standard treatment: n=125 (49%) and pembrolizumab monotherapy: n=124 (48%) vs. standard treatment: n=133 (52%)] (see Table 29). Based on best response of stable disease or better, The Kaplan-Meier curve for OS for the TPS 50% population is shown in Figure 22. PFS and ORR results are reported from an interim analysis at a median follow-up of 11 months. Immune-related adverse reactions have also occurred after the last dose of pembrolizumab. The primary efficacy outcome was OS in the ITT population. The baseline and prognostic disease characteristics of the study population of KEYNOTE-052 included a proportion of patients eligible for a carboplatin-based combination, for whom the benefit has been assessed in a comparative study (KEYNOTE-361). 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. Clinical particulars 4.1 Therapeutic indications 4.2 Posology and method of administration 4.3 Contraindications 4.4 Special warnings and precautions for use 4.5 Interaction with other medicinal products and other forms of interaction Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of pembrolizumab (see Description of selected adverse reactions below). For precautions to be taken before administering the vaccine, see section 4.4. The clinical significance of this is unknown. These results should be interpreted in the context of the open-label study design and therefore taken cautiously. Assessment of tumour status was performed every 9 weeks for the first 45 weeks, and every 12 weeks thereafter. /Rotate 0 If not used immediately, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at 2C to 8C. 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. Secondary efficacy outcome measures were objective response rate (ORR) and response duration. 14 0 obj /Type /Page Table 36 summarises the key efficacy measures and Figures 28 and 29 show the Kaplan Meier curves for updated PFS and OS based on the final analysis with a median follow-up time of 38.1 months (range: 0.2 to 58.7 months). Patients treated with KEYTRUDA must be given the patient alert card and be informed about the risks of KEYTRUDA (see also package leaflet). In general, the frequency of adverse reactions for pembrolizumab combination therapy is observed to be higher than for pembrolizumab monotherapy or chemotherapy alone, reflecting the contributions of each of these components (see sections 4.2 and 4.8). referring specialist and the MHRA yellow card scheme 1. Severe skin reactions resolved in 93 patients, 2 with sequelae. The same scoring system was used for metastatic melanoma (MEL score). Storage at 25C is not the recommended storage or shipping condition but may guide decisions for use in case of temporary temperature excursions during the 9-month storage at 2C to 8C. It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. You have accepted additional cookies. Enrolment of adolescents completed in June 2021. Patients were randomised (1:1) to one of the following treatment arms via intravenous infusion: Pembrolizumab 200 mg 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 pembrolizumab 200 mg every 3 weeks. Microsoft Word - 1646658070014998238_spc-doc.doc 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. The dual primary efficacy outcome measures were PFS as assessed by BICR using RECIST 1.1 and OS. 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. A partnership between NHS organisations in South East London: Bexley, Bromley, Greenwich, Lambeth, Lewisham and Southwark Clinical Commissioning Groups (CCGs) and GSTFT/KCH /SLAM/ Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust Immunogenicity in Adolescents 12 through 17 years of age. These results reflect enrolment that occurred during the time period when the B.1.17 (Alpha) variant was circulating in the UK. Participants with clinically stable underlying comorbidity were included as were participants with well-controlled HIV infection. Following collection of sufficient safety data to support application for emergency use authorisation, initial recipients of placebo were invited to receive two injections of Nuvaxovid 21 days apart and initial recipients of Nuvaxovid to receive two injections of placebo 21 days apart (blinded crossover). Patients with non-squamous NSCLC could receive pemetrexed maintenance.). 17 0 obj 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. Hyperthyroidism may be managed symptomatically. In the Hodgkin lymphoma population (n=22), in patients aged 11 years to 17 years, the baseline characteristics were median age 15 years; 64% male; 68% White; 77% had a Lansky/Karnofsky scale 90-100 and 23% had scale 70-80. /S /D You can change your cookie settings at any time. This page includes guidance for pharmaceutical companies and regulators on how to prepare and review summaries of product characteristics (SmPCs) for human medicines. The study excluded patients with nasopharyngeal carcinoma, active autoimmune disease that required systemic therapy within 2 years of treatment, a medical condition that required immunosuppression, or who were previously treated with 3 or more systemic regimens for recurrent and/or metastatic HNSCC. 16 0 obj All participants were offered the opportunity to continue to be followed in the study. /Length 29 0 R EIR SPC Flooring. Nuvaxovid was assessed in individuals 18 years of age and older. 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