Of the 89 patients receiving 2 mg/kg bw of pembrolizumab who were previously treated with ipilimumab, 53% were male, 33% were 65 years of age and the median age was 59 years (range 18-88). Figure 25: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-581. These SPC applications are geographically-limited to Northern Ireland, unless/until a separate authorisation is also issued by the MHRA to cover the remainder of the UK, i.e. Pembrolizumab must be permanently discontinued for any Grade 3 immune-related adverse reaction that recurs and for any Grade 4 immune-related adverse reaction. Each multidose vial contains a colourless to slightly yellow, clear to mildly opalescent dispersion free from visible particles. /Kids [7 0 R 8 0 R 9 0 R 10 0 R 11 0 R 12 0 R 13 0 R] Use of pembrolizumab in urothelial carcinoma for patients who are considered ineligible for cisplatin-containing chemotherapy and whose tumours express PD-L1 with CPS 10. Hepatitis has been reported in patients receiving pembrolizumab (see section 4.8). Pembrolizumab should not be used during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. . %PDF-1.4 KEYNOTE-006: Controlled study in melanoma patients nave to treatment with ipilimumab. When reporting, please include the vaccine brand and batch/lot number, if available. You can change your cookie settings at any time. There is an increased risk of myocarditis and pericarditis following vaccination with Nuvaxovid. Fever was observed more frequently in adolescents aged 12 through to 17 years compared to adults, with the frequency being very common after the second dose in adolescents. Treatment with pembrolizumab or placebo continued until RECIST 1.1-defined progression of disease as determined by BICR, unacceptable toxicity, or a maximum of 24 months. Based on best response of stable disease or better, For RCC patients treated with KEYTRUDA in combination with axitinib, see the SmPC regarding dosing of axitinib. 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). Hyperthyroidism may be managed symptomatically. Reporting forms and information can be found at https://coronavirus-yellowcard.mhra.gov.uk or you can search for MHRA Yellow Card in the Google Play or Apple App Store. The efficacy of pembrolizumab in combination with chemotherapy as neoadjuvant treatment and then continued as monotherapy as adjuvant treatment after surgery was investigated in the randomised, double-blind, multicentre, placebo-controlled study KEYNOTE-522. Common sites of metastases in patients were lung (69%), lymph node (46%), and bone (26%). From a microbiological point of view, the product, once diluted, should be used immediately. They are based on information in the SPC of the medicine. For Grade 4 haematological toxicity, only in patients with cHL, KEYTRUDA should be withheld until adverse reactions recover to Grades 0-1. null 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. Key eligibility criteria were metastatic non-squamous NSCLC, no prior systemic treatment for metastatic NSCLC, and no EGFR or ALK genomic tumour aberrations. All rights reserved. Use of pembrolizumab for treatment of patients with advanced or recurrent MSI-H or dMMR endometrial carcinoma. The median time to onset of hypophysitis was 5.9 months (range 1 day to 17.7 months). Novavax CZ a.s. 1. Please regularly check this information as it is often updated. /Parent 3 0 R For instructions on handling and disposal of the vaccine, see section 6.6. Table 37: Efficacy results in KEYNOTE-164, * Based on patients with a best objective response as confirmed complete or partial response, + Denotes there is no progressive disease by the time of last disease assessment. Neutralising antibody responses were compared with those observed in seronegative/PCR-negative adult participants aged 18 through 25 years from the adult main study (Per Protocol Immunogenicity ( PP-IMM) Analysis Set) as shown in Table 3. See section 4.8 for how to report adverse reactions. Scientific guidelines with SmPC recommendations. It is not. Patients without disease progression were treated for up to 24 months (up to 35 cycles). Corticosteroids should be administered for Grade 2 events (initial dose of 1-2 mg/kg/day prednisone or equivalent followed by a taper); pembrolizumab should be withheld for Grade 2 or Grade 3 colitis, and permanently discontinued for Grade 4 or recurrent Grade 3 colitis (see section 4.2). Where we have identified any third party copyright information you will need to obtain permission from the copyright holders concerned. KEYTRUDA, in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery, is indicated for the treatment of adults with locally advanced, or early-stage triple-negative breast cancer at high risk of recurrence (see section 5.1). Table 9: Efficacy results by PD-L1 expression in KEYNOTE-006. Among the 305 patients in KEYNOTE-024, baseline characteristics were: median age 65 years (54% age 65 or older); 61% male; 82% White, 15% Asian; and ECOG performance status 0 and 1 in 35% and 65%, respectively. 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. Table 14: Efficacy results in KEYNOTE-189, Pembrolizumab + Pemetrexed + Platinum Chemotherapy, Placebo + Pemetrexed + Platinum Chemotherapy, * A total of 113 patients (57%) who discontinued study treatment in the placebo plus chemotherapy arm crossed over to receive monotherapy pembrolizumab or received a checkpoint inhibitor as subsequent therapy, Pembrolizumab may be restarted within 12 weeks after last dose of KEYTRUDA if the adverse reaction recovers to Grade 1 and corticosteroid dose has been reduced to 10 mg prednisone or equivalent per day. /Length 6 0 R Table 34: Efficacy results in KEYNOTE-581 by MSKCC prognostic group, * Median follow-up: 26.5 months (data cutoff 28 August 2020), 6 weeks) with no > Grade 2 treatment-related adverse events to axitinib and with blood pressure well controlled to 150/90 mm Hg were permitted dose escalation of axitinib to 7 mg twice daily. Name of the medicinal product 2. /Rotate 0 Table 32 summarises the efficacy measures by IMDC risk category based on the final OS analysis at a median follow-up of 37.7 months. /Contents 27 0 R Sixteen percent (16%) had disease progression following platinum-containing neoadjuvant or adjuvant chemotherapy, and 84% had received 1-2 prior systemic regimens for metastatic disease. There was no statistically significant difference between pembrolizumab and chemotherapy with respect to PFS. No dose adjustment is needed for patients with mild or moderate renal impairment. stream The geographical scope of the SPC is then also expanded. Two patients experienced hepatic VOD, one of which was fatal. It will take only 2 minutes to fill in. Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. Vaccination should be postponed in individuals suffering from an acute severe febrile illness or acute infection. The study population characteristics were: median age of 65 years (range: 29 to 88); 55% age 65 or older; 81% male; 77% White; ECOG performance status of 0 (29%) and 1 (71%); and 8% with treated brain metastases at baseline. 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%. The safety and efficacy of pembrolizumab were also investigated in KEYNOTE-042, a multicentre, controlled study for the treatment of previously untreated locally advanced or metastatic NSCLC. 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). 1. The primary efficacy analysis set (PP-EFF) included 2,770 participants who received either Nuvaxovid (n = 1,408) or placebo (n = 1,362), received two doses (Dose 1 on day 0; Dose 2 on day 21), did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infection through 7 days after the second dose. Patients who experienced GVHD after their transplant procedure may be at an increased risk for GVHD after treatment with pembrolizumab. << Withdraw the required volume up to 4 mL (100 mg) of concentrate and transfer into an intravenous bag containing sodium chloride 9 mg/mL (0.9%) or glucose 50 mg/mL (5%) to prepare a diluted solution with a final concentration ranging from 1 to 10 mg/mL. Based on Miettinen and Nurminen method stratified by PD-L1 status, platinum chemotherapy and smoking status, Figure 11: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-189 (intent to treat population), Figure 12: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-189 (intent to treat population). In patients with HNSCC treated with pembrolizumab in combination with platinum and 5-FU chemotherapy (n=276), the incidence of hypothyroidism was 15.2%, all of which were Grade 1 or 2. Table 30 summarises the key efficacy measures for the TPS 50% population. A decision should be made whether to discontinue breast-feeding or to discontinue pembrolizumab, taking into account the benefit of breast-feeding for the child and the benefit of pembrolizumab therapy for the woman. 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%). The median time to onset of severe skin reactions was 3.0 months (range 2 days to 25.5 months). Seventy-six percent of patients received 2 or more prior lines of therapy. The PD-1 receptor is a negative regulator of T-cell activity that has been shown to be involved in the control of T-cell immune responses. Among the 304 patients in KEYNOTE-204, there is a subpopulation consisting of 112 patients who failed a transplant before enrolling and 137 who failed 2 or more prior therapies and were ineligible for ASCT at the time of enrolment. KEYNOTE-024: Controlled study of NSCLC patients nave to treatment. Physicians should consider the benefit/risk balance of the available treatment options (pembrolizumab monotherapy or pembrolizumab in combination with chemotherapy) before initiating treatment in patients with HNSCC whose tumours express PD-L1 (see section 5.1). Assessment of tumour status was performed every 9 weeks. Email Address: Registration No: What companies run services between Andalusia, Spain and Seville, Spain? This medicinal product is subject to additional monitoring. 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&! Nominal two-sided p-Value based on the stratified Cochran-Mantel-Haenszel (CMH) test. 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