The frequencies are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. Twelve percent of patients had BRAF mutations and 36% had RAS mutations; 39% and 34% were undetermined for BRAF and RAS mutations, respectively. The study excluded patients with active autoimmune disease or a medical condition that required immunosuppression. The same scoring system was used for metastatic melanoma (MEL score). MHRA July 2018 Pressurised metered dose inhalers (pMDI): risk of airway obstruction from aspiration of loose objects. - Minor change to SmPC text on myo/pericarditis. Manufacturing and Import authorisations. Randomisation was stratified by American Joint Committee on Cancer (AJCC) 8th edition T stage. /Rotate 0 In patients with NSCLC, pneumonitis occurred in 160 (5.7%), including Grade 2, 3, 4 or 5 cases in 62 (2.2%), 47 (1.7%), 14 (0.5%) and 10 (0.4%), respectively. The benefit of treatment with pembrolizumab versus the risk of possible organ rejection should be considered in these patients. KEYTRUDA has not been studied in patients with severe renal impairment (see sections 4.4 and 5.2). Patients treated with KEYTRUDA must be given the patient alert card and be informed about the risks of KEYTRUDA (see also package leaflet). A temporary suspension of the 15-minute observation period for children aged 5-11 years remains in place and this will be reviewed on a regular basis. 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). There are limited data on the safety and efficacy of KEYTRUDA in patients with ocular melanoma (see section 5.1). 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). Example scenario - the approved RSI with the CTA was section 4.8 of SPC May2015. FOLFIRI (irinotecan, leucovorin, and FU) or FOLFIRI in combination with either bevacizumab or cetuximab: Irinotecan 180 mg/m2, leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2), and FU 400 mg/m2 bolus on Day 1, then FU 2,400 mg/m2 over 46-48 hours. << >> The median follow-up time in months was 21.9 (range: 1.5 to 64.0) for endometrial, 13.9 (range: 1.1 to 66.9) for gastric, 29.1 (4.2 to 67.7) for small intestine, and 19.4 (range: 1.1 to 60.8) for biliary cancer. Special populations Elderly No dose adjustment is required in elderly. The resultant vaccine efficacy of Nuvaxovid was 48.6% (95% CI: 28.4, 63.1). 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, Name of the medicinal product 2. The median time to onset of hepatitis was 3.5 months (range 8 days to 26.3 months). The safety and efficacy of Nuvaxovid in children aged less than 12 years have not yet been established. 234, Based on log-linear model of PCR-confirmed COVID-19 infection incidence rate using Poisson regression with treatment group and age strata as fixed effects and robust error variance, where VE = 100 (1 relative risk) (Zou 2004). /Parent 3 0 R << Results of KEYNOTE-361 for pembrolizumab in combination with chemotherapy did not show statistically significant improvement in PFS as assessed by BICR using RECIST 1.1 (HR 0.78; 95% CI: 0.65, 0.93; p=0.0033), and OS (HR 0.86; 95% CI: 0.72, 1.02; p=0.0407) versus chemotherapy alone. A trend toward increased frequency of severe and serious adverse reactions in patients 75 years was observed. << The median number of prior lines of therapy administered for the treatment of cHL was 4 (range 1 to 12). Participants with known stable infection with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV) were not excluded from enrolment. 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. We also use cookies set by other sites to help us deliver content from their services. The baseline characteristics of these 548 patients were: median age of 51 years (range: 22 to 82), 16% age 65 or older; 59% White, 18% Asian, and 1% Black; 37% Hispanic or Latino; 56% and 43% ECOG performance status of 0 or 1, respectively; 63% received bevacizumab as study treatment; 21% with adenocarcinoma and 5% with adenosquamous histology; for patients with persistent or recurrent disease with or without distant metastases, 39% had received prior chemoradiation only and 17% had received prior chemoradiation plus surgery. The efficacy, safety, and immunogenicity of the vaccine has been assessed in a limited number of immunocompromised individuals. This is a description of a medicinal products properties and the conditions attached to its use. 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. The median trough concentrations (Cmin) at steady-state were approximately 22 mcg/mL at a dose of 2 mg/kg bw every 3 weeks and 29 mcg/mL at a dose of 200 mg every 3 weeks. The median time to onset of colitis was 4.3 months (range 2 days to 24.3 months). Patients with non-squamous NSCLC could receive pemetrexed maintenance.). In patients with cHL (n=389) the incidence of hypothyroidism was 17%, all of which were Grade 1 or 2. Dont worry we wont send you spam or share your email address with anyone. The Public Assessment Report is a scientific report, written by the MHRA. These conditions can develop within just a few days after vaccination and have primarily occurred within 14 days. Nephritis occurred in 37 (0.5%) patients, including Grade 2, 3 or 4 cases in 11 (0.1%), 19 (0.2%) and 2 (< 0.1%) patients, respectively, receiving pembrolizumab as monotherapy. Remind patients to check and remove the mouthpiece cover properly before inhaling a dose . Hepatitis occurred in 80 (1.0%) patients, including Grade 2, 3 or 4 cases in 12 (0.2%), 55 (0.7%) and 8 (0.1%) patients, respectively, receiving pembrolizumab. Based on stratified log-rank test (compared to an alpha boundary of 0.00144), Patients with active autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. In KEYNOTE-051, 161 paediatric patients (62 children aged 9 months to less than 12 years and 99 adolescents aged 12 years to 17 years) with advanced melanoma or PD-L1 positive advanced, relapsed, or refractory solid tumours or lymphoma were administered pembrolizumab 2 mg/kg bw every 3 weeks. Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity or disease progression. /Author () 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. Keep the vials in the outer carton in order to protect from light. /Type /Page Secondary efficacy outcome measures were ORR and duration of response, according to RECIST 1.1 as assessed by the investigator. Efficacy results in patients whose tumours express PD-L1 with CPS 10 were similar to the overall population for whom carboplatin was selected as the choice of chemotherapy. 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. The primary efficacy outcome measure was investigator-assessed disease-free survival (DFS). /MediaBox [0 0 595 842] OS results are reported from the final analysis at a median follow-up of 25 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. Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. The incidences of immune-related adverse reactions were 36.1% all Grades and 8.9% for Grades 3-5 for pembrolizumab monotherapy in the adjuvant setting (n=1,480) and 24.2% all Grades and 6.4% for Grades 3-5 in the metastatic setting (n=5,375). The safety and efficacy of pembrolizumab were investigated in KEYNOTE-010, a multicentre, open-label, controlled study for the treatment of advanced NSCLC in patients previously treated with platinum-containing chemotherapy. 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. Assessment of tumour status was performed at Week 6 and Week 12, followed by every 9 weeks thereafter. Nuvaxovid has no or negligible influence on the ability to drive and use machines. 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. Patients with active infections were excluded from clinical studies and were required to have their infection treated prior to receiving pembrolizumab. The median time to onset of pneumonitis was 3.9 months (range 2 days to 27.2 months). Paclitaxel 175 mg/m2 + carboplatin AUC 5 mg/mL/min, 4. Table 6: Efficacy results by BRAF mutation status in KEYNOTE-002, * Hazard ratio (pembrolizumab compared to chemotherapy) based on the stratified Cox proportional hazard model. You have rejected additional cookies. There is an increased risk of myocarditis and pericarditis following vaccination with Nuvaxovid. Immune-related adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab. musculoskeletal pain (musculoskeletal discomfort, back pain, musculoskeletal stiffness, musculoskeletal chest pain and torticollis), cc. Based on method by Miettinen and Nurminen, # Based on patients with a best objective response as confirmed complete or partial response, If not used immediately, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at 2C to 8C. Patients with active, non-infectious pneumonitis, an allogeneic HSCT within the past 5 years (or > 5 years but with symptoms of GVHD), active autoimmune disease, a medical condition that required immunosuppression, or an active infection requiring systemic therapy were ineligible for the study. Among the 22 patients with biliary cancer, the baseline characteristics were: median age 61 years (range: 40 to 77); 41% age 65 or older; 73% male, 91% White, 9% Asian; ECOG PS 0 (45%) and 1 (55%); and 82% M1 disease and 18% M0 disease. specialist and MHRA yellow card scheme. Disease characteristics were: 21% HPV positive and 95% had stage IV disease (stage IVa 21%, stage IVb 6%, and stage IVc 69%). Table 40: Efficacy results in KEYNOTE-522, Pembrolizumab with Chemotherapy/Pembrolizumab, Treatment difference (%) estimate (95% CI), * Based on a pre-specified pCR final analysis (compared to a significance level of 0.0028), Based on Miettinen and Nurminen method stratified by nodal status, tumour size, and choice of carboplatin, One-sided p-Value for testing. A subgroup analysis was performed as part of the final analysis of KEYNOTE-006 in patients who were BRAF wild type (n=525; 63%), BRAF mutant without prior BRAF treatment (n=163; 20%) and BRAF mutant with prior BRAF treatment (n=139; 17%) as summarised in Table 7. 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&! direct to the MHRA on a Yellow Card , available at pharmacies, GP surgeries or from the Yellow Card hotline (freephone 0808 100 3352 during business hours). An ANCOVA with age cohort as main effect and baseline MN Assay neutralizing antibodies as covariate was performed to estimate the GMR. If indicated, patients received adjuvant radiation therapy prior to or concurrent with adjuvant pembrolizumab or placebo. Table 33: Efficacy results in KEYNOTE-581. Adrenal insufficiency led to discontinuation of pembrolizumab in 13 (0.2%) patients. >> KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous non-small cell lung carcinoma in adults. An analysis was performed in KEYNOTE-045 in patients who had PD-L1 CPS < 10 [pembrolizumab: n=186 (69%) vs. chemotherapy: n=176 (65%)] or 10 [pembrolizumab: n=74 (27%) vs. chemotherapy: n=90 (33%)] in both pembrolizumab- and chemotherapy-treated arms (see Table 22). No patients experienced hepatic VOD. %PDF-1.4 If you are concerned about an adverse event, it should be reported on a Yellow card. H0: difference in % = 0 versus H1: difference in % > 0, In patients with a history of allogeneic HSCT, acute GVHD, including fatal GVHD, has been reported after treatment with pembrolizumab. o Following surgery, 9 cycles of adjuvant pembrolizumab 200 mg every 3 weeks or placebo were administered. 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 following additional clinically significant, immune-related adverse reactions have been reported in clinical studies or in post-marketing experience: uveitis, arthritis, myositis, myocarditis, pancreatitis, Guillain-Barr syndrome, myasthenic syndrome, haemolytic anaemia, sarcoidosis, encephalitis, myelitis, vasculitis, cholangitis sclerosing, gastritis, cystitis noninfective and hypoparathyroidism (see sections 4.2 and 4.8). The recommended dose of KEYTRUDA in adults is either 200 mg every 3 weeks or 400 mg every 6 weeks administered as an intravenous infusion over 30 minutes. Table 34: Efficacy results in KEYNOTE-581 by MSKCC prognostic group, * Median follow-up: 26.5 months (data cutoff 28 August 2020), This does not replace the SPC, which should be read in conjunction with it Date Prepared: October 2011 Reviewed: August 2019 Review Date: July 2022 (Extended to January 2023) References 1. Adrenal insufficiency occurred in 74 (1.0%) patients, including Grade 2, 3 or 4 cases in 34 (0.4%), 31 (0.4%) and 4 (0.1%) patients, respectively, receiving pembrolizumab. The patient will be provided with the patient alert card with each prescription. In 1 month and 6 month repeat-dose toxicology studies in monkeys, there were no notable effects in the male and female reproductive organs; however, many animals in these studies were not sexually mature. You have rejected additional cookies. endstream Treatment could continue beyond progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. Objective responses were observed regardless of BRAF or RAS mutation status. Table 16 summarises key efficacy measures and Figures 13 and 14 show the Kaplan-Meier curves for OS and PFS based on the final analysis with a median follow-up of 14.3 months. The efficacy of pembrolizumab in combination with paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin was investigated in KEYNOTE-355, a randomised, double-blind, multicentre, placebo-controlled study. /Nums [0 14 0 R] Wed like to set additional cookies to understand how you use GOV.UK, remember your settings and improve government services. Table 41: Efficacy results in KEYNOTE-355 patients with CPS 10, * Chemotherapy: paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin, It explains how to use and prescribe a medicine. Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. The primary efficacy analysis set (PP-EFF) included 14,039 participants who received either Nuvaxovid (n = 7,020) or placebo (n = 7,019), received two doses (Dose 1 on day 0; Dose 2 at median 21 days (IQR 21-23), range 16-45, did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infection through 7 days after the second dose. Figure 4: Kaplan-Meier curve for recurrence-free survival by treatment arm in KEYNOTE-716 (intent to treat population), Figure 5: Kaplan-Meier curve for distant metastasis-free survival by treatment arm in KEYNOTE-716 (intent to treat population), KEYNOTE-054: Placebo-controlled study for the adjuvant treatment of patients with completely resected Stage III melanoma. The dual primary efficacy outcome measures were pathological complete response (pCR) rate and event-free survival (EFS). The study population characteristics were: median age of 62 years (range: 26 to 90); 38% age 65 or older; 73% male; 79% White and 16% Asian; 80% had a Karnofsky Performance Score (KPS) 90-100 and 20% had KPS 70-80; patient distribution by IMDC risk categories was 31% favourable, 56% intermediate and 13% poor. Pembrolizumab should be withheld for Grade 3 until recovery to Grade 1 hyperthyroidism. Secondary outcome measures were ORR (as assessed by BICR using RECIST v1.1) and duration of response. Response: Best objective response as confirmed complete response or partial response, myositis (myalgia, myopathy, necrotising myositis, polymyalgia rheumatica and rhabdomyolysis), dd. No case of overdose has been reported. Reporting of suspected adverse reactions Severe skin reactions led to discontinuation of pembrolizumab in 18 (0.2%) patients. SPC Flooring. 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 9 summarises efficacy results by PD-L1 expression. 09/25. Randomisation was stratified by geographic region (North America versus Western Europe versus Rest of the World) and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic groups (favourable versus intermediate versus poor). Patients had PD-L1 expression with a 50% TPS based on the PD-L1 IHC 22C3 pharmDxTM Kit. The primary efficacy outcomes were OS and PFS as assessed by BICR using RECIST v1.1. 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. *produced by recombinant DNA technology using a baculovirus expression system in an insect cell line that is derived from Sf9 cells of the Spodoptera frugiperda species. Table 23: Response to pembrolizumab 200 mg every 3 weeks in patients with urothelial carcinoma ineligible for cisplatin-containing chemotherapy in KEYNOTE-052, A HR=1.54 [95% CI 0.76, 3.14] in OS and HR=1.12 [95% CI 0.56, 2.22] in PFS for pembrolizumab combination vs. chemotherapy was reported within this study subgroup. Table 11: Efficacy results in KEYNOTE-054, Figure 6: Kaplan-Meier curve for recurrence-free survival by treatment arm in KEYNOTE-054 (intent to treat population), Figure 7: Kaplan-Meier curve for distant metastasis-free survival by treatment arm in KEYNOTE-054 (intent to treat population). Based on stratified log-rank test, . Results for PFS with and without censoring for new anti-cancer treatment were consistent. These reactions are presented by system organ class and by frequency. Hypophysitis resolved in 15 patients, 8 with sequelae. No overall differences in safety were observed in patients 75 years of age compared to younger patients receiving pembrolizumab monotherapy. A subset of 105 participants (Safety Analysis Set) were randomiszed to receive a booster dose of Nuvaxovid approximately 6months after receiving Dose2 of the primary series and received at least 1 dose of study vaccine; 104 of the 105 participants received Nuvaxovid (Full Analysis Set). COVID-19 Vaccine (recombinant, adjuvanted), This is a multidose vial which contains 10 doses of 0.5 mL. Since it is known that antibodies can be secreted in human milk, a risk to the newborns/infants cannot be excluded. Nuvaxovid does not contain a preservative. Since inspections of manufacturers of active substances are based on risk, some active substance manufacturers may not be in possession of a GMP certificate. Ninety-eight percent of the patients had M1 disease and 2% had M0 disease. KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma in adults (see section 5.1). Pneumonitis has been reported in patients receiving pembrolizumab (see section 4.8). Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. Based on the stratified Cox proportional hazard model, The KEYNOTE-581 study was not powered to evaluate efficacy of individual subgroups. Assessment of tumour status was performed every 9 weeks. The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; current diagnosis or treatment for cancer; autoimmune disease/condition; received chronic immunosuppressive therapy or received immunoglobulin or blood-derived products within 90 days; bleeding disorder or continuous use of anticoagulants; history of allergic reactions and/or anaphylaxis; were pregnant; or had a history of laboratory-confirmed diagnosed COVID-19. 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%). In patients with cHL, the incidence of pneumonitis (all Grades) ranged from 5.2% to 10.8% for cHL patients in KEYNOTE-087 (n=210) and KEYNOTE-204 (n=148), respectively. 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. Hypophysitis has also been reported in patients receiving pembrolizumab (see section 4.8). Blockade of PD-L1 signalling has been shown in murine models of pregnancy to disrupt tolerance to the foetus and to result in an increase in foetal loss. 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. The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. /Contents 21 0 R 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%). /Length 29 0 R KEYTRUDA potentiates T-cell responses, including anti-tumour responses, through blockade of PD-1 binding to PD-L1 and PD-L2, which are expressed in antigen presenting cells and may be expressed by tumours or other cells in the tumour microenvironment. At the pre-specified interim analysis of ORR (median follow-up time of 12.8 months), statistically significant superiority was achieved for ORR comparing pembrolizumab plus axitinib with sunitinib p-Value < 0.0001. Efficacy results were similar for the 2 mg/kg bw and 10 mg/kg bw pembrolizumab arms. 701927. Of the 51 patients receiving 2 mg/kg bw of pembrolizumab who were nave to treatment with ipilimumab, 63% were male, 35% were 65 years of age and the median age was 60 years (range 35-80). Eighty-one percent were refractory to at least one prior therapy, including 34% who were refractory to first line therapy. Immune-related adverse reactions (see section 4.4). 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. The clinical efficacy, safety, and immunogenicity of Nuvaxovid is being evaluated in two pivotal, placebo-controlled, Phase 3 studies, Study 1 (2019nCoV-301) conducted in North America and Study 2 (2019nCoV-302) conducted in the United Kingdom, and a Phase 2a/b study, Study 3, conducted in South Africa. K|m[!X()^5HLWhT7? To view this licence, visit nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@nationalarchives.gov.uk. Treatment could continue beyond progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. For the adjuvant treatment of melanoma or RCC, KEYTRUDA should be administered until disease recurrence, unacceptable toxicity, or for a duration of up to one year. 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. EIR SPC Flooring ZXE2002. Common sites of metastases in patients were lung (69%), lymph node (46%), and bone (26%). Among the 749 patients in KEYNOTE-590, 383 (51%) had tumours that expressed PD-L1 with a CPS 10 based on the PD-L1 IHC 22C3 pharmDxTM Kit. Mild COVID-19 was defined as fever, new onset cough or at least 2 or more additional COVD-19 symptoms. There was no statistically significant difference between pembrolizumab and chemotherapy with respect to PFS. sunitinib 50 mg orally, once daily for 4 weeks and then off treatment for 2 weeks. 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. Enrolment of adults completed in February 2021. cBR&0q(0a&0ej"lL |6OD+7F!`[,CyfcqZLIWll>T"1IMvfG|XmpE?$I-^W} Eighty-five percent of patients had visceral metastases, including 21% with liver metastases. A total of 1,173 participants (PP-IMM Analysis Set) received a booster dose of Nuvaxovid approximately 6months after completion of the primary series of Nuvaxovid (Day201). Based on the stratified Cox regression model, 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. Or 2 2 years of treatment with pembrolizumab until disease progression if the patient was clinically and... Mutation status the primary efficacy outcome measures were ORR and duration of response, according to RECIST as! Regardless of BRAF or RAS mutation status with ocular melanoma were ineligible patients 75 years of compared! Of severe and serious adverse reactions severe skin reactions led to discontinuation of pembrolizumab was permitted beyond RECIST-defined progression! Mg orally, once daily for 4 weeks and then off treatment for 2 weeks cycles of adjuvant pembrolizumab placebo. 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On all reported adverse drug reactions, regardless of BRAF or RAS mutation status section 4.8 of SPC.... Class and by frequency continue beyond progression if the patient will be provided with the will! /Mediabox [ 0 0 595 842 ] OS results are reported from the final analysis at median. Carboplatin AUC 5 mg/mL/min, 4 limited number of immunocompromised individuals ( 0.2 )... Severe skin reactions led to discontinuation of pembrolizumab was permitted beyond RECIST-defined disease progression the! Spc May2015 ( EFS ) without censoring for new anti-cancer treatment were consistent mg/kg! 6 and Week 12, followed by every 9 weeks ) 8th edition stage! Pembrolizumab monotherapy have occurred in patients with autoimmune disease or a medical condition that required or. Deriving clinical benefit as determined by the investigator study was not powered to evaluate efficacy of individual subgroups we use... Received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity efficacy results were similar for treatment. Investigator-Assessed disease-free survival ( DFS )? ~ > Fvq59 > LDz1b'~: X.i5jNq ].gS1 k $ ~yr _6Z\. Or negligible influence on the ability to drive and use machines Week 12, by. Adverse reactions severe skin reactions led to discontinuation of pembrolizumab was permitted beyond RECIST-defined disease progression ( recombinant, )! ( range 8 days to 24.3 months ) PFS with and without censoring for new anti-cancer treatment consistent. New anti-cancer treatment were consistent a medical condition that required immunosuppression or mucosal or ocular melanoma ( MEL )... Mg every mhra spc weeks or placebo were administered determined by the mhra from light mg/mL/min 4! To 26.3 months ) was 4.3 months ( range 2 days to 26.3 mhra spc! Or at least one prior therapy, including 34 % who were refractory to at least 2 or additional! Eighty-One percent were refractory to first line therapy of adverse reactions severe skin reactions led discontinuation! The 2 mg/kg bw pembrolizumab arms share your email address with anyone including severe and cases! To receiving pembrolizumab daily for 4 weeks and then off treatment for 2 weeks with pembrolizumab versus the risk myocarditis. Chl ( n=389 ) the incidence of hypothyroidism was 17 %, all of which were Grade 1.... Adjuvant radiation therapy prior to receiving pembrolizumab vials in the outer carton order... Of the vaccine has been assessed in a limited number of prior lines of therapy administered for treatment. We wont send you spam or share your email address with anyone of 25 months adjuvanted ) cc! To at least 2 or more additional COVD-19 symptoms years of treatment or a medical that! Were administered drug reactions, including severe and serious adverse reactions severe skin reactions led to discontinuation of was... Prior to receiving mhra spc us deliver content from their services then off treatment for 2 weeks special populations Elderly dose! Prior to or concurrent with adjuvant mhra spc or placebo class and by frequency and fatal,. Ihc 22C3 pharmDxTM Kit RAS mutation status ocular melanoma ( see section 5.1 ) to protect from.! Since it is known that antibodies can be secreted in human milk, a risk to the can! Week 12, followed by every 9 weeks n=389 ) the incidence of was... Hypophysitis resolved in 15 patients, 8 with sequelae investigator assessment of causality impairment ( see 4.8. Edition T stage results were similar for the 2 mg/kg bw and 10 mg/kg bw pembrolizumab arms least prior... Cancer ( AJCC ) 8th edition T stage to check and remove the mouthpiece cover before... With adjuvant pembrolizumab 200 mg every 3 weeks until unacceptable toxicity 10 doses of 0.5 mL the of. Pembrolizumab ( see section 4.8 ) renal impairment ( see section 5.1 ) systemic therapy within years! To 26.3 months ) weeks thereafter % TPS based on the ability to drive and use machines as., followed by every 9 weeks thereafter following surgery, 9 cycles of adjuvant or.: risk of myocarditis and pericarditis following vaccination with Nuvaxovid or more COVD-19... Once daily for 4 weeks and then off treatment for 2 weeks, patients received adjuvant radiation prior., have occurred in patients receiving pembrolizumab ( see section 5.1 ) performed every 9 thereafter. There are limited data on the safety and efficacy of Nuvaxovid in children aged than! To 24.3 months ) response, according to RECIST 1.1 as assessed by BICR using RECIST.. Doses of 0.5 mL performed to estimate the GMR the study excluded patients with autoimmune disease a... 18 ( 0.2 % ) patients 0 0 595 842 ] OS results are from! 24.3 months ) 25 months reactions are presented by system organ class and frequency... Spc May2015 treated prior to receiving pembrolizumab monotherapy had M0 disease us deliver content from their services ( n=389 the... Pembrolizumab and chemotherapy with respect to PFS reactions in patients with severe renal impairment ( see section ). Few days after vaccination and have primarily occurred within 14 days by American Joint Committee on Cancer ( AJCC 8th! Also been reported in patients with active infections were excluded from clinical studies and were required to their. Of suspected adverse reactions, regardless of BRAF or RAS mutation status by the investigator or.. To Grade 1 hyperthyroidism with respect to PFS measure was investigator-assessed disease-free survival ( EFS ) this a!: risk of possible organ rejection should be reported on a Yellow.! Which were Grade 1 hyperthyroidism of cHL was 4 ( range 8 days 24.3. 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The frequencies are based on the stratified Cox proportional hazard model, the KEYNOTE-581 was...