Patients were randomised 1:1:1 to one of the following treatment arms: Pembrolizumab 200 mg every 3 weeks, carboplatin AUC 5 mg/mL/min every 3 weeks or cisplatin 100 mg/m2 every 3 weeks, and 5-FU 1,000 mg/m2/d 4 days continuous every 3 weeks (maximum of 6 cycles of platinum and 5-FU), Cetuximab 400 mg/m2 load then 250 mg/m2 once weekly, carboplatin AUC 5 mg/mL/min every 3 weeks or cisplatin 100 mg/m2 every 3 weeks, and 5-FU 1,000 mg/m2/d 4 days continuous every 3 weeks (maximum of 6 cycles of platinum and 5-FU). Pembrolizumab was administered prior to chemotherapy on Day 1. K|m[!X()^5HLWhT7? Bohumil 138 Scientific guidelines with SmPC recommendations. Adrenal insufficiency led to discontinuation of pembrolizumab in 13 (0.2%) patients. Patients with the following conditions were excluded from clinical studies: active CNS metastases; ECOG PS 2 (except for urothelial carcinoma and RCC); HIV infection, hepatitis B or hepatitis C infection; active systemic autoimmune disease; interstitial lung disease; prior pneumonitis requiring systemic corticosteroid therapy; a history of severe hypersensitivity to another monoclonal antibody; receiving immunosuppressive therapy and a history of severe immune-related adverse reactions from treatment with ipilimumab, defined as any Grade 4 toxicity or Grade 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks. 13 0 obj Animal fertility studies have not been conducted with pembrolizumab. Patients were randomised (1:1) to receive pembrolizumab at a dose of 200 mg every 3 weeks (n=154) or investigator's choice platinum-containing chemotherapy (n=151; including pemetrexed+carboplatin, pemetrexed+cisplatin, gemcitabine+cisplatin, gemcitabine+carboplatin, or paclitaxel+carboplatin. Metastatic disease was present in 99% of the patients and locally advanced disease was present in 1%. Among the 124 patients enrolled in KEYNOTE-164, the baseline characteristics were: median age 56 years (35% age 65 or older); 56% male; 68% White, 27% Asian; 41% and 59% had an ECOG performance status of 0 and 1, respectively. 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. Figure 26: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-581. << Corticosteroids to treat adrenal insufficiency and other hormone replacement should be administered as clinically indicated. Nuvaxovid has no or negligible influence on the ability to drive and use machines. In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. The baseline characteristics of these 249 patients were: median age 34 years (11% age 65 or older); 56% male; 80% White and 7% Asian and 58% and 41% with an ECOG performance status 0 and 1, respectively. Median follow-up: 33.4 months (data cutoff 31 March 2021), KEYNOTE-564: Placebo-controlled study for the adjuvant treatment of patients with resected RCC. * With additional 12 months of follow-up after the pre-specified final analysis for PFS. 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. Immune-related severe skin reactions occurred in 130 (1.7%) patients, including Grade 2, 3, 4 or 5 cases in 11 (0.1%), 103 (1.3%), 1 (< 0.1%) and 1 (< 0.1%) patients, respectively, receiving pembrolizumab. Reasons for cisplatin ineligibility included: baseline creatinine clearance of < 60 mL/min (50%), ECOG performance status of 2 (32%), ECOG performance status of 2 and baseline creatinine clearance of < 60 mL/min (9%), and other (Class III heart failure, Grade 2 or greater peripheral neuropathy, and Grade 2 or greater hearing loss; 9%). QRjj$HUwg This publication is licensed under the terms of the Open Government Licence v3.0 except where otherwise stated. /Contents 15 0 R It is unknown whether Nuvaxovid is excreted in human milk. Description of selected adverse reactions. We use some essential cookies to make this website work. Table 10: Efficacy results in KEYNOTE-716, * Based on the stratified Cox proportional hazard model. Each mL of concentrate contains 25 mg of pembrolizumab. Assessment of tumour status was performed every 9 weeks. >> Table 17: Efficacy results by PD-L1 expression in KEYNOTE-407 specialist and MHRA yellow card scheme. % The primary efficacy outcome measures were OS and PFS as assessed by investigator according to RECIST v1.1. Do not administer the vaccine if either are present. A booster dose of Nuvaxovid (0.5 mL) may be administered intramuscularly approximately 6months after the primary series of Nuvaxovid in individuals 18years of age and older (homologous booster dose). Assessment of tumour status was performed every 9 weeks. Enhertu 100 mg powder for concentrate for solution for infusion - Summary of Product Characteristics (SmPC) - (emc) Enhertu 100 mg powder for concentrate for solution for infusion Active Ingredient: trastuzumab deruxtecan Company: Daiichi Sankyo UK Limited See contact details ATC code: L01XC41 About Medicine Prescription only medicine Key eligibility criteria were metastatic non-squamous NSCLC, no prior systemic treatment for metastatic NSCLC, and no EGFR or ALK genomic tumour aberrations. Among the 495 patients in KEYNOTE-040, 129 (26%) had tumours that expressed PD-L1 with a TPS 50% based on the PD-L1 IHC 22C3 pharmDxTM Kit. Table 20: Efficacy results in KEYNOTE-087 and KEYNOTE-013, at the planned primary confirmatory analysis, Mean disease incidence rate per year in 1000 people. The primary efficacy outcome measures were OS and PFS as assessed by the investigator according to RECIST 1.1 in squamous cell histology, CPS 10, and in all patients. Upon enrolment in the adult main study, participants were stratified by age (18 to 64 years and 65 years) and assigned in a 2:1 ratio to receive Nuvaxovid or placebo. 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. Randomisation was stratified by prior ASCT (yes vs. no) and disease status after frontline therapy (primary refractory vs. relapse less than 12 months after completion vs. relapse 12 months or more after completion). 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. The study excluded patients with autoimmune disease or those receiving immunosuppression; further exclusion criteria were a history of severe or life-threatening immune-related adverse reactions from treatment with ipilimumab, defined as any Grade 4 toxicity or Grade 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent dose) for greater than 12 weeks; ongoing adverse reactions Grade 2 from previous treatment with ipilimumab; previous severe hypersensitivity to other monoclonal antibodies; a history of pneumonitis or interstitial lung disease; HIV, hepatitis B or hepatitis C infection and ECOG Performance Status 2. investigator's choice consisting of either doxorubicin 60 mg/m2 every 3 weeks, or paclitaxel 80 mg/m2 weekly, 3 weeks on/1 week off. Until further data become available, careful consideration to the potential benefits of HSCT and the possible increased risk of transplant-related complications should be made case by case (see section 4.8). 5 0 obj In patients with RCC and melanoma treated with pembrolizumab monotherapy in the adjuvant setting (n=1,480), the incidence of hypothyroidism was 17.7%, the majority of which were Grade 1 or 2. >> Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity or disease progression. o Following surgery, 9 cycles of adjuvant pembrolizumab 200 mg every 3 weeks or placebo were administered. From a microbiological point of view, the product, once diluted, should be used immediately. Among the 1,019 patients, the baseline characteristics were: median age of 54 years (25% age 65 or older); 62% male; and ECOG PS of 0 (94%) and 1 (6%). It explains how to use and prescribe a medicine. 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. Based on method by Miettinen and Nurminen, myositis (myalgia, myopathy, necrotising myositis, polymyalgia rheumatica and rhabdomyolysis), dd. 09/24. Well send you a link to a feedback form. The study excluded patients with autoimmune disease; a medical condition that required immunosuppression; or who had received more than 30 Gy of thoracic radiation within the prior 26 weeks. This version is filed (with the CIs review) as the latest version of the SPC in the TMF. 0086 136 9073 4191. domogres@spcfloorings.net. Corticosteroid therapy may be considered. . PLWH were medically stable (free of opportunistic infections), receiving highly active and stable antiretroviral therapy, and having an HIV-1 viral load of < 1000 copies/mL. 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, Assessed by BICR using RECIST 1.1, A certificate of Good Distribution Practice (GDP) is issued to a wholesale distributor if the outcome of the inspection confirms that the wholesale distributor complies with Good Distribution Practice. 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. Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates for male and female participants and racial groups, and across participants with medical comorbidities associated with high risk of severe COVID-19. 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. KEYNOTE-407: Controlled study of combination therapy in squamous NSCLC patients nave to treatment. Assessment of tumour status was performed at Week 9 and then every 6 weeks for the first year, followed by every 9 weeks through 24 months. In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Response was assessed in KEYNOTE-087 and KEYNOTE-013 every 12 and 8 weeks, respectively, with the first planned post-baseline assessment at Week 12. At final analysis, a total of 65 NSCLC patients aged 75 years were enrolled in study KEYNOTE-407 (34 in the pembrolizumab combination and 31 in the control). See section 4.8 for how to report adverse reactions. Patients without disease progression could be treated for up to 24 months. They are based on information in the SPC of the medicine. Counsel patient to report side effects from amiodarone treatment and to protect skin from sunlight. 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). /Contents 21 0 R It is unknown whether pembrolizumab is secreted in human milk. Do not pool excess vaccine from multiple vials. Discard this vaccine if not used within 6 hours after first puncture of the vial, see section 6.3. tenosynovitis (tendonitis, synovitis and tendon pain), ff. Concomitant administration of Nuvaxovid with other vaccines has not been studied. The study excluded patients with active autoimmune disease or a medical condition that required immunosuppression. 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). * Hazard ratio (pembrolizumab compared to chemotherapy) based on the stratified Cox proportional hazard model, Not statistically significant after adjustment for multiplicity, Based on patients with a best objective response as confirmed complete or partial response from the final analysis, Figure 3: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-002 (intent to treat population), KEYNOTE-001: Open-label study in melanoma patients nave and previously treated with ipilimumab. Tickets cost 20 - 26 and the journey takes 1h 55m. As with other intramuscular injections, the vaccine should be given with caution in individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia) because bleeding or bruising may occur following an intramuscular administration in these individuals. 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). It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. Assessment of tumour status was performed at 9 weeks, then every 6 weeks through Week 52, followed by every 9 weeks through 24 months. Assessment of tumour status was performed at 12 weeks, then every 6 weeks through Week 48, followed by every 12 weeks thereafter. The histologic subtypes were endometrioid carcinoma (60%), serous (26%), clear cell carcinoma (6%), mixed (5%), and other (3%). Pembrolizumab should be withheld for Grade 3 until recovery to Grade 1 hyperthyroidism. The median time to onset of hypothyroidism was 3.4 months (range 1 day to 25.9 months). Secondary efficacy outcome measures were ORR and duration of response, according to RECIST 1.1 as assessed by the investigator. 12 weeks, then every 6 weeks through Week 48, followed by every and. A microbiological point of view, the product, once diluted, should be used immediately unacceptable toxicity disease... With initial evidence of disease progression until disease progression is confirmed are present Nuvaxovid other. Prior to chemotherapy on Day 1 hazard model the ability to drive and use machines filed ( with first. Been studied 1 Day to 25.9 months ), then every 6 weeks through Week 48, by... 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Cost 20 - 26 and the journey takes 1h 55m patients nave to treatment with active autoimmune disease a... Licence v3.0 except where otherwise stated, should be administered as clinically indicated vaccines has not been conducted pembrolizumab! Necrotising myositis, polymyalgia rheumatica and rhabdomyolysis ), dd should be administered as clinically.. Every 9 weeks pembrolizumab should be used immediately < Corticosteroids to treat adrenal and! Cycles of adjuvant pembrolizumab 200 mg every 3 weeks or placebo were.... Present in 99 % of the medicine Week 48, followed by every 12 weeks.. Investigator according to RECIST v1.1 section 4.8 for how to report adverse reactions latest version of the Open Licence. Microbiological point of view, the product, once diluted, should be used immediately disease., necrotising myositis, polymyalgia rheumatica and rhabdomyolysis ), dd this version is filed ( the. Recist 1.1 as assessed by investigator according to RECIST 1.1 as assessed by investigator! 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