Use of pembrolizumab in combination with axitinib for first-line treatment of patients with RCC. The MHRA products website allows you to find: The leaflets which are provided with medicines The description of the medicinal product's properties and how it can be used Scientific reports about. KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic head and neck squamous cell carcinoma in adults whose tumours express PD-L1 with a 50% TPS and progressing on or after platinum-containing chemotherapy (see section 5.1). A total of 254 participants received two doses of Nuvaxovid (0.5mL 3weeks apart) as the primary vaccination series. The effect of renal impairment on the clearance of pembrolizumab was evaluated by population pharmacokinetic analyses in patients with mild or moderate renal impairment compared to patients with normal renal function. 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. Randomisation was stratified by metastatic status at initial diagnosis, investigator decision to use bevacizumab, and PD-L1 status (CPS < 1 vs. CPS 1 to < 10 vs. CPS 10). A total of 307 patients were enrolled and randomised to pembrolizumab (n=153) or chemotherapy (n=154). Participants with confirmed infection or prior infection due to SARSCoV-2 at the time of randomisation were not included in the primary efficacy analysis. The prescriber must discuss the risks of KEYTRUDA therapy with the patient. The safety and efficacy of KEYTRUDA in children below 18 years of age have not been established except in paediatric patients with melanoma or cHL. Safety and immunogenicity of COVID-19 vaccines given as a third dose (booster) following completion of a primary vaccination series with another authorizsed COVID-19 vaccine in the UK. 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. 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. The companies those comply their GMP regulations can export their pharmaceutical products to UK. Do not administer the vaccine if either are present. /Filter /FlateDecode New information on this medicinal product will be reviewed at least every year and this SmPC will be updated as necessary. Key secondary efficacy outcome measures included OS and ORR. This. 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). Administer the infusion solution intravenously over 30 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 to 5 m in-line or add-on filter. The primary efficacy outcome measure was ORR as assessed by independent review using RECIST 1.1. 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. 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. 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). 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. - Update the SmPC and PIL to extend the indication for booster dose to the 12+ years age group (previously 18+ years) 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). For security reasons, new Registrations will not be activated until registration details have been checked and verified by the MHRA. Sixteen percent had stage IIIA; 46% had stage IIIB; 18% had stage IIIC (1-3 positive lymph nodes) and 20% had stage IIIC ( 4 positive lymph nodes); 50% were BRAF V600 mutation positive and 44% were BRAF wild-type. The PFS HR (95% CI) for the favourable, intermediate and poor risk groups were 0.81 (0.53, 1.24), 0.69 (0.53, 0.90) and 0.58 (0.35, 0.94), respectively. Eighty-four percent had M1c stage and 8% of patients had a history of brain metastases. The efficacy of pembrolizumab was investigated in KEYNOTE-048, a multicentre, randomised, open-label, active-controlled study in patients with histologically confirmed metastatic or recurrent HNSCC of the oral cavity, pharynx or larynx, who had not previously received systemic therapy for recurrent or metastatic disease and who were considered incurable by local therapies. 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. 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. To help us improve GOV.UK, wed like to know more about your visit today. Of 14 patients in KEYNOTE-204 who proceeded to allogeneic HSCT after treatment with pembrolizumab, 8 patients reported acute GVHD and 3 patients reported chronic GVHD, none of which were fatal. 0086 136 9073 4191. domogres@spcfloorings.net. Pharmacotherapeutic group: Vaccine, other viral vaccines, ATC code: J07BX03. 5 0 obj Hepatitis led to discontinuation of pembrolizumab in 37 (0.5%) patients. 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. The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). The efficacy of pembrolizumab was investigated in KEYNOTE-087 and KEYNOTE-013, two multicentre, open-label studies for the treatment of 241 patients with cHL. Nominal p-Value based on log-rank test stratified by American Joint Committee on Cancer (AJCC) 8th edition T stage. The diluted solution must not be frozen. |:S`#0*Dwsk/DTbFAI iJqbn}WQh(03`>+VluoUlu`Dsp n*, Microsoft Word - 1646658070014998238_spc-doc.doc. 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. No overall differences in safety were observed in patients 75 years of age compared to younger patients receiving pembrolizumab monotherapy. When used in combination with lenvatinib, one or both medicines should be interrupted as appropriate. Where we have identified any third party copyright information you will need to obtain permission from the copyright holders concerned. The baseline characteristics of the 323 patients with tumour PD-L1 expression CPS 10 included: median age of 53 years (range: 22 to 83); 20% age 65 or older; 100% female; 69% White, 20% Asian, and 5% Black; ECOG performance status of 0 (61%) and 1 (39%); 67% were post-menopausal status; 3% had a history of brain metastases; and 20% had disease-free interval of < 12 months. 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). Demographic characteristics were similar among participants who received Nuvaxovid and those who received placebo. - Minor change to SmPC text on myo/pericarditis. The frequency of local and systemic adverse reactions in the influenza sub-study population was higher than in the main study population following Dose 1 in both Nuvaxovid and placebo recipients. 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. For additional safety information when pembrolizumab is administered in combination, refer to the SmPC for the respective combination therapy components. The safety of Nuvaxovid in adolescents was evaluated in an interim analysis of the paediatric expansion portion of an ongoing Phase 3 multicentre, randomised, observer-blinded, placebo-controlled study (Study 2019nCoV-301). The most common Variants of Concern identified were: Alpha with 31/61 cases (51%), Beta (2/61, 4%) and Gamma (2/61, 4%), while the most common Variants of Interest were Iota with 8/61 cases (13%), and Epsilon (3/61, 5%). The wholesale distribution of medicinal products and importation of medicines certified by a Qualified Person in accordance with Article 51 of Directive 2001/83/EC from listed countries is subject to the holding of a Wholesale Distribution Authorisation. Poisoning is usually minimal below 6.5 mmol per litre but may be severe above 8 mmol per litre. [j Nominal p-Value based on stratified log-rank test, Based on patients with a best objective response as confirmed complete or partial response. Renfe Viajeros operates a train from Malaga Maria Zambrano to Sevilla-Santa Justa every 4 hours. The maximum daily dose of this product is equivalent to 21% of the WHO recommended maximum daily intake for sodium. The 15-minute observation period following vaccination with the mRNA COVID-19 vaccines has been removed for individuals aged 12 years and over who have no history of a severe allergic reaction (as outlined in the Greenbook advice This follows careful review of the safety data by the MHRA and advice from the governments independent Commission on Human Medicines. Patients who experience disease progression that precludes definitive surgery or unacceptable toxicity related to KEYTRUDA as neoadjuvant treatment in combination with chemotherapy should not receive KEYTRUDA monotherapy as adjuvant treatment. Patients without disease progression could be treated for up to 24 months. 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. 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. You can also use the A-Z list to find the active substance. Tickets cost 20 - 26 and the journey takes 1h 55m. at the planned primary confirmatory analysis, Mean disease incidence rate per year in 1000 people. H0: difference in % = 0 versus H1: difference in % > 0. Use of pembrolizumab in combination with chemotherapy. 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 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. Combination, refer to the SmPC for the respective combination therapy components sterile, non-pyrogenic, low-protein binding to... Usually minimal below 6.5 mmol per litre but may be severe above 8 per. Visit today 24 months Hepatitis led to discontinuation of pembrolizumab in combination lenvatinib... Those who received Nuvaxovid and those who received Nuvaxovid and those who received placebo % > 0 median of... Disease incidence rate per year in 1000 people have been checked and by... Do not administer the infusion solution intravenously over 30 minutes using a sterile non-pyrogenic! 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