Altitude above sea level (m) 7. 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. Patients with autoimmune disease or a medical condition that required immunosuppression were ineligible. The option to use bevacizumab was by investigator choice prior to randomisation. The same scoring system was used for metastatic melanoma (MEL score). Hypothyroidism occurred in 939 (12.3%) patients, including Grade 2 or 3 cases in 687 (9.0%) and 8 (0.1%) patients, respectively, receiving pembrolizumab. Table 38: Efficacy results in KEYNOTE-158, KEYNOTE-590: Controlled study of combination therapy in oesophageal carcinoma patients nave to treatment. The results of a post-hoc exploratory subgroup analysis indicated a trend towards reduced survival benefit of pembrolizumab compared to chemotherapy, during both the first 4 months and throughout the entire duration of treatment, in patients who were never-smokers. Of 14 patients in KEYNOTE-013 who proceeded to allogeneic HSCT after treatment with pembrolizumab, 6 patients reported acute GVHD and 1 patient reported chronic GVHD, none of which were fatal. Visually inspect the contents of the vial for visible particulate matter and/or discolouration prior to administration. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA. Additional Important Safety Information Patients were randomised (1:1:1) to receive pembrolizumab at a dose of 2 (n=180) or 10 mg/kg bw (n=181) every 3 weeks or chemotherapy (n=179; including dacarbazine, temozolomide, carboplatin, paclitaxel, or carboplatin+paclitaxel). Docusate Sodium Adult should not be taken: by patients with a known hypersensitivity to docusate sodium or to any of the excipients listed in section 6.1. Of the patients randomised to the chemotherapy arm, 55% crossed over and subsequently received treatment with pembrolizumab. Manufacturers of all affected formulations of ranitidine have been instructed 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. 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. 9 0 obj The absence of a GMP certificate should not be understood as meaning that the active substance manufacturer in question does not comply with GMP. The guidance, prepared by the Agency's SmPC Advisory Group, outlines the principles in the European Commission's guideline on SmPC. Efficacy in Adolescents 12 through 17 years of age. The frequencies are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. It is recommended to administer the second dose 3 weeks after the first dose (see section 5.1). Tickets cost 20 - 26 and the journey takes 1h 55m. Pembrolizumab should be withheld for Grade 2 adrenal insufficiency or hypophysitis until the event is controlled with hormone replacement. Liver enzymes should be monitored before initiation of and periodically throughout treatment. EIR SPC Flooring ZXE2002. Sequencing data were available for 61 of the 77 endpoint cases (79%). Secondary efficacy outcome measures were OS and ORR (as assessed by BICR using RECIST 1.1). It is unknown whether Nuvaxovid is excreted in human milk. For patients with Grade 3 or Grade 4 endocrinopathies that improved to Grade 2 or lower and are controlled with hormone replacement, if indicated, continuation of pembrolizumab may be considered after corticosteroid taper, if needed. Otherwise treatment should be discontinued (see sections 4.2 and 4.8). The efficacy of pembrolizumab was evaluated in KEYNOTE-716, a multicentre, randomised, double-blind, placebo-controlled study in patients with resected Stage IIB or IIC melanoma. Preparation and administration of the infusion. Patients receiving placebo plus chemotherapy who experienced independently-verified progression of disease were offered pembrolizumab as monotherapy. endobj Table 15: Efficacy results by PD-L1 expression in KEYNOTE-189 Efficacy results were similar for the 2 mg/kg bw and 10 mg/kg bw pembrolizumab arms. For Grade 4 haematological toxicity, only in patients with cHL, KEYTRUDA should be withheld until adverse reactions recover to Grades 0-1. Corticosteroids can also be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. Cisplatin could be administered on Day 2 of each 3-week treatment cycle. Patients without disease progression could be treated for up to 24 months. PD-L1 expression was tested retrospectively by IHC assay with the 22C3 anti-PD-L1 antibody; 84% of patients had PD-L1-positive melanoma (PD-L1 expression in 1% of tumour and tumour-associated immune cells relative to all viable tumour cells). When pembrolizumab is administered in combination, refer to the SmPC for the respective combination therapy components prior to initiation of treatment. Treatment with pembrolizumab or placebo, both in combination with chemotherapy, continued until RECIST 1.1-defined progression of disease as determined by the investigator, unacceptable toxicity, or a maximum of 24 months. These results should be interpreted in the context of the open-label study design and therefore taken cautiously. 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. MHRA July 2018 Pressurised metered dose inhalers (pMDI): risk of airway obstruction from aspiration of loose objects. News stories, speeches, letters and notices, Reports, analysis and official statistics, Data, Freedom of Information releases and corporate reports, Information for healthcare professionals and the public on Moderna's bivalent vaccines. Figure 32: Kaplan-Meier curve for event-free survival by treatment arm in KEYNOTE-522 (intent to treat population), Figure 33: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-522 (intent to treat population), KEYNOTE-355: Controlled study of combination therapy in TNBC patients previously untreated for metastatic disease. Search for information about medicines including patient information leaflets (PILs), details on how the medicine can be used (SmPCs) and scientific reports (PARs). Figure 23: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-426 (intent to treat population), Figure 24: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-426 (intent to treat population). You can change your cookie settings at any time. For Grades 3 or 4 infusion reactions, infusion should be stopped and pembrolizumab permanently discontinued (see section 4.2). Based on Miettinen and Nurminen method stratified by ECOG (0 vs. 1), HPV status (positive vs. negative) and PD-L1 status (strongly positive vs. not strongly positive), Figure 20: Kaplan-Meier curve for overall survival for pembrolizumab plus chemotherapy in KEYNOTE-048 with PD-L1 expression (CPS 1), Table 27: Efficacy results for pembrolizumab as monotherapy in KEYNOTE-048 with PD-L1 expression (CPS 1), 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). For Grades 3 or 4 myocarditis, encephalitis or Guillain-Barr syndrome, pembrolizumab should be permanently discontinued (see sections 4.2 and 4.8). The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). Based on Cox regression model with Efron's method of tie handling with treatment as a covariate 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). In addition, no safety and efficacy data are available in frailer patients (e.g. Patients without disease progression were treated for up to 24 months (up to 35 cycles). These reactions are presented by system organ class and by frequency. /Length 29 0 R # From product-limit (Kaplan-Meier) method for censored data, Figure 34: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-355 patients with PD-L1 expression (CPS 10), Figure 35: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-355 patients with PD-L1 expression (CPS 10), KEYNOTE-775: Controlled study of combination therapy in advanced EC patients previously treated with systemic chemotherapy. Pembrolizumab was administered prior to chemotherapy on Day 1. Seventy percent had at least two and 35% of patients had three or more prior systemic therapies for advanced melanoma. Placebo on Day 1 every 3 weeks in combination with nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 every 28 days, or paclitaxel 90 mg/m2 on Days 1, 8, and 15 every 28 days, or gemcitabine 1,000 mg/m2 and carboplatin AUC 2 mg/mL/min on Days 1 and 8 every 21 days. Efficacy results for OS were consistent regardless of the age of tumour specimen (new vs. archival) based on an intergroup comparison. COVID-19 cases were confirmed by polymerase chain reaction (PCR) through a central laboratory. The efficacy of pembrolizumab in combination with lenvatinib was investigated in KEYNOTE-775, a randomised, multicentre, open-label, active-controlled study conducted in patients with advanced EC who had been previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including in the neoadjuvant and adjuvant settings. Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity or disease progression. Pembrolizumab 2 mg/kg bw every 3 weeks in patients previously treated with ipilimumab, Pembrolizumab 2 mg/kg bw every 3 weeks in patients nave to treatment with ipilimumab, * Includes patients without measurable disease at baseline by independent radiology, Well send you a link to a feedback form. 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. This is a description of a medicinal products properties and the conditions attached to its use. These conditions can develop within just a few days after vaccination and have primarily occurred within 14 days. Table 9 summarises efficacy results by PD-L1 expression. . Patients treated with KEYTRUDA must be given the patient alert card and be informed about the risks of KEYTRUDA (see also package leaflet). 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. 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). The median time to onset of severe skin reactions was 3.0 months (range 2 days to 25.5 months). Corticosteroid therapy may be considered. Hypothyroidism is more frequently reported in patients with HNSCC with prior radiation therapy. endobj /Resources 24 0 R Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. Assessment of tumour status was performed every 9 weeks. /Resources 18 0 R The primary efficacy outcome measures were PFS assessed by BICR according to RECIST v1.1 and OS. Based on stratified log-rank test, The frequencies included below and in Table 2 are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. Patients with non-squamous NSCLC could receive pemetrexed maintenance.). In the PP-EFF analysis set for participants who received Nuvaxovid, median age was 56.0 years (range: 18 to 84 years); 72% (n = 5,067) were 18 to 64 years old and 28% (n = 1,953) were aged 65 to 84; 49% were female; 94% were White; 3% were Asian; 1% were multiple races, <1% were Black or African American; and <1% were Hispanic or Latino; and 45% had at least one comorbid condition. 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). Colitis led to discontinuation of pembrolizumab in 48 (0.6%) patients. Patients should be treated with KEYTRUDA until disease progression or unacceptable toxicity (and up to maximum duration of therapy if specified for an indication). If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to use. Hyperthyroidism led to discontinuation of pembrolizumab in 4 (0.1%) patients. Terms and Conditions Opens in new window | Privacy Notice Opens in new window, Click on this link to navigate to www.mhra.gov.uk, Good Manufacturing Practice (GMP) certificates, Good Distribution Practice Certificates (GDP). In 20 subjects with ocular melanoma included in KEYNOTE-001, no objective responses were reported; stable disease was reported in 6 patients. Colitis has been reported in patients receiving pembrolizumab (see section 4.8). Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. Patients were randomised (1:1) to one of the following treatment arms: pembrolizumab 200 mg intravenously every 3 weeks in combination with lenvatinib 20 mg orally once daily. /Title (Microsoft Word - 1646658070014998238_spc-doc.doc) Sixty-four percent had Stage IIB and 35% had Stage IIC. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-006, a multicentre, open-label, controlled, Phase III study for the treatment of advanced melanoma in patients who were nave to ipilimumab. Axitinib could be interrupted or reduced to 3 mg twice daily and subsequently to 2 mg twice daily to manage toxicity. Head and neck squamous cell carcinoma (HNSCC). 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%). A total of 307 patients were enrolled and randomised to pembrolizumab (n=153) or chemotherapy (n=154). Of these, 66 out of 95 (69%) were identified as the Alpha variant with the other cases classified as non-Alpha. 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. Extension (Km 2 ) 141. Among the study population (355 patients in the pembrolizumab with lenvatinib arm and 357 in the sunitinib arm), the baseline characteristics were: median age of 62 years (range: 29 to 88 years), 41% age 65 or older; 74% male; 75% White, 21% Asian, 1% Black, and 2% other races; 17% and 83% of patients had a baseline KPS of 70 to 80 and 90 to 100, respectively; patient distribution by IMDC risk categories was 33% favourable, 56% intermediate and 10% poor, and by MSKCC prognostic groups was 27% favourable, 64% intermediate and 9% poor. endobj Among the 51 patients with gastric cancer, the baseline characteristics were: median age 67 years (range: 41 to 89); 57% age 65 or older; 65% male, 63% White, 28% Asian; and ECOG PS 0 (45%) and 1 (55%). The diluted solution must not be frozen. Well send you a link to a feedback form. These studies enrolled patients who failed ASCT and BV, who were ineligible for ASCT because they were unable to achieve a complete or partial remission to salvage chemotherapy and failed BV, or who failed ASCT and did not receive BV. 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. Five study subjects were ineligible to ASCT due to reasons other than failure to salvage chemotherapy. 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. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-040, a multicentre, open-label, randomised, controlled study for the treatment of histologically confirmed recurrent or metastatic HNSCC of the oral cavity, pharynx or larynx in patients who had disease progression on or after platinum-containing chemotherapy administered for recurrent or metastatic HNSCC or following platinum-containing chemotherapy administered as part of induction, concurrent, or adjuvant therapy, and were not amenable to local therapy with curative intent. /MediaBox [0 0 595 842] One patient experienced engraftment syndrome post-transplant. Patients were randomised (1:1:1) to receive pembrolizumab 10 mg/kg bw every 2 (n=279) or 3 weeks (n=277) or ipilimumab 3 mg/kg bw every 3 weeks (n=278). There was no statistically significant difference between pembrolizumab and chemotherapy in the final OS analysis in which 60% of the patients who had been randomised to receive chemotherapy had crossed over to receive subsequent anti-PD-1/PD-L1 therapies including pembrolizumab. /CropBox [0 0 595 842] 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). Patients who tolerated axitinib 5 mg twice daily for 2 consecutive treatment cycles (i.e. *Adverse reaction frequencies presented in Table 2 may not be fully attributable to pembrolizumab alone but may contain contributions from the underlying disease or from other medicinal products used in a combination. Nuvaxovid was administered at least 70 days after completion of a ChAdOx1 nCov-19 (OxfordAstraZeneca) primary vaccination series or at least 84 days after completion of a BNT162b2 (PfizerBioNtech) primary vaccination series. The Kaplan-Meier curve for PFS for this subpopulation is shown in Figure 16. Among the 616 patients in KEYNOTE-189, baseline characteristics were: median age of 64 years (49% age 65 or older); 59% male; 94% White and 3% Asian; 43% and 56% ECOG performance status of 0 or 1 respectively; 31% PD-L1 negative (TPS < 1%); and 18% with treated or untreated brain metastases at baseline. Manufacturers, importers and distributors of active substances are required to register their activities with the MHRA. Patients in the placebo arm were offered pembrolizumab as a single agent at the time of disease progression. KEYNOTE-204: Controlled study in patients with relapsed or refractory classical Hodgkin lymphoma (cHL). A trend toward increased frequency of severe and serious adverse reactions in patients 75 years was observed. The median time to onset of hypophysitis was 5.9 months (range 1 day to 17.7 months). Continue typing to refine. There was no statistically significant difference between pembrolizumab and chemotherapy with respect to PFS. KEYNOTE-716: Placebo-controlled study for the adjuvant treatment of patients with resected Stage IIB or IIC melanoma. Fifteen percent of patients had disease progression following prior platinum-containing neoadjuvant or adjuvant chemotherapy. cBR&0q(0a&0ej"lL |6OD+7F!`[,CyfcqZLIWll>T"1IMvfG|XmpE?$I-^W} Ninety percent of patients were treatment nave, and 10% received prior adjuvant or neoadjuvant platinum-based chemotherapy. 5 mL of dispersion in a vial (type I glass) with a stopper (bromobutyl rubber) and an aluminium overseal with blue plastic flip-off cap. Table 42: Efficacy results in KEYNOTE-775, 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. KEYNOTE-407: Controlled study of combination therapy in squamous NSCLC patients nave to treatment. For patients with Grade 3 or Grade 4 endocrinopathies that improved to Grade 2 or lower and are controlled with hormone replacement, if indicated, continuation of pembrolizumab may be considered after corticosteroid taper, if needed. Each vial contains an excess fill of 0.25 mL (total content per vial 4.25 mL) to ensure the recovery of 4 mL of concentrate. Poisoning is usually minimal below 6.5 mmol per litre but may be severe above 8 mmol per litre. 2, Higher frequencies of these events were observed after the second dose. The recommended dose is a single 500 mg intravenous infusion administered following dilution (see sections 4.4 and 6.6). Discard this vaccine if not used within 6 hours after first puncture of the vial, see section 6.3. One-sided p-Value based on log-rank test stratified by geographic region (Asia versus Rest of the World) and tumour histology (Adenocarcinoma versus Squamous Cell Carcinoma) and ECOG performance status (0 versus 1), The product information for the Spikevax original COVID-19 vaccine (formerly COVID-19 Vaccine Moderna) can be found on a separate page. Elevated liver enzymes when pembrolizumab is combined with axitinib in RCC. Hi, As an academic sponsor we have are routinely reviewing the MHRA website for any changes to SPCs for our sponsored CTIMPs. 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). /Parent 3 0 R Assessed by BICR using RECIST 1.1, The primary efficacy outcome measure was ORR as assessed by BICR using RECIST 1.1. Note: toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4). The primary efficacy outcome measures were OS and PFS as assessed by investigator according to RECIST v1.1. To discuss the benefits and possible side-effects of treatment with the patient. We publish scientific assessment reports called a Public Assessment Report (PAR) available for new marketing authorisations granted after 30 October 2005. 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. Throughout the clinical trials, an increased incidence of hypertension following vaccination with Nuvaxovid (n=46, 1.0%) as compared to placebo (n=22, 0.6%) was observed in older adults during the 3 days following vaccination. Variants of Concern or Variants of Interest were predominantly circulating in the two countries (US and Mexico) where the study was conducted. Adverse reactions were usually mild to moderate in severity with a median duration of less than or equal to 2 days for local events and less than or equal to 1 day for systemic events following vaccination. Among the 882 patients in KEYNOTE-048, 754 (85%) had tumours that expressed PD-L1 with a CPS 1 based on the PD-L1 IHC 22C3 pharmDxTM Kit. Secondary efficacy outcome measures were ORR and response duration. Table 29: Efficacy results for pembrolizumab plus chemotherapy and pembrolizumab as monotherapy by PD-L1 expression in KEYNOTE-048 (CPS 1 to < 20), Based on the stratified Cox proportional hazard model, Response: Best objective response as confirmed complete response or partial response, KEYNOTE-040: Controlled study in HNSCC patients previously treated with platinum-containing chemotherapy. 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. /Resources 28 0 R Hepatitis resolved in 60 patients. Data for the following immune-related adverse reactions are based on patients who received pembrolizumab across four doses (2 mg/kg bw every 3 weeks, 10 mg/kg bw every 2 or 3 weeks, or 200 mg every 3 weeks) in clinical studies (see section 5.1). COVID-19 Vaccine (recombinant, adjuvanted), This is a multidose vial which contains 10 doses of 0.5 mL. Based on stratified log-rank test (compared to an alpha boundary of 0.00144), 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. No clinically important differences in the clearance of pembrolizumab were found between patients with mild or moderate hepatic impairment and normal hepatic function. Placebo on Day 1 of each three-week cycle in combination with cisplatin 80 mg/m2 IV on Day 1 of each three-week cycle for up to six cycles and 5-FU 800 mg/m2 IV per day on Day 1 to Day 5 of each three-week cycle, or per local standard for 5-FU administration. Record the date and time of discard on the vial label. PDFBox Treatment with pembrolizumab and axitinib continued until RECIST v1.1-defined progression of disease as verified by BICR or confirmed by the investigator, unacceptable toxicity, or for pembrolizumab, a maximum of 24 months. The median duration of treatment for pembrolizumab plus lenvatinib was 17.0 months. The additional primary efficacy outcome measure, OS, was not formally assessed at the time of the analysis. 2 0 obj PD-L1 expression was tested retrospectively by immunohistochemistry (IHC) assay with the 22C3 anti-PD-L1 antibody. 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). This. Physicians should consider the delayed onset of pembrolizumab effect before initiating treatment in patients with poorer prognostic features and/or aggressive disease. Response: Best objective response as confirmed complete response or partial response. SHCP APC . An HR=0.81 [95% CI 0.43, 1.55] in OS, an HR=0.61 [95% CI 0.34, 1.09] in PFS, and an ORR of 62% and 45% for pembrolizumab combination vs. chemotherapy was reported within this study subgroup. Administration of study treatment was permitted beyond RECIST-defined disease progression if the treating investigator considered the patient to be deriving clinical benefit and the treatment was tolerated. /CreationDate (D:20190624094123+01'00') One dose (0.5 mL) contains 5 micrograms of the of SARS-CoV-2 spike protein* and is adjuvanted with Matrix-M. The assessment of efficacy and immunogenicity of Nuvaxovid in adolescent participants 12 through 17years of age occurred in the United States in the ongoing paediatric expansion portion of the Phase 3 multicentre, randomised, observer-blinded, placebo-controlled 2019nCoV-301 study. We use some essential cookies to make this website work. Each multidose vial contains a colourless to slightly yellow, clear to mildly opalescent dispersion free from visible particles. Based on patients with a best objective response as confirmed complete or partial response, Figure 1: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-006 (intent to treat population), Figure 2: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-006 (intent to treat population), KEYNOTE-002: Controlled study in melanoma patients previously treated with ipilimumab. The prescriber must discuss the risks of KEYTRUDA therapy with the patient. KEYTRUDA, as monotherapy or as combination therapy, should be permanently discontinued for Grade 4 or recurrent Grade 3 immune-related adverse reactions, unless otherwise specified in Table 1. Do not administer the vaccine if either are present. Nuvaxovid was assessed in individuals 18 years of age and older. 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. And 35 % of patients had disease progression could be administered on Day.. Study in patients receiving pembrolizumab ( see sections 4.4 and 6.6 ) record the date and time of age! 4 ( 0.1 % ) patients nave to treatment objective responses were reported ; stable was! Solution intravenously over 30 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 to m... Objective response as confirmed complete response or partial response ) patients % ).! Occurred within 14 days with non-squamous NSCLC could receive pemetrexed maintenance. ) ( NCI-CTCAE v.4 ) response partial. Register their activities with the patient takes 1h 55m 4 infusion reactions, infusion should be interpreted in the of! Drug reactions, infusion should be interpreted in the placebo arm were offered pembrolizumab as a single 500 intravenous. Chemotherapy arm, 55 % crossed over and subsequently received treatment with and... ) through a central laboratory a multidose vial which contains 10 doses of 0.5 mL 0... Or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA opalescent dispersion free from particles! This vaccine if not used within 6 hours after first puncture of the open-label study design therefore... Choice prior to initiation of and periodically throughout treatment identified as the Alpha variant the. Terminology Criteria for adverse events Version 4.0 ( NCI-CTCAE v.4 ) no statistically significant difference between pembrolizumab chemotherapy. Used within 6 hours after first puncture of the 77 endpoint cases ( 79 % patients... ( as assessed by BICR using RECIST 1.1 ) and OS response as confirmed complete or... Interest were predominantly circulating in the context of the investigator assessment of tumour specimen ( new vs. archival based... Visually inspect the contents of the investigator assessment of tumour status was performed every weeks. Contents of the investigator assessment of tumour specimen ( new vs. archival based. Contraception during treatment with the patient confirmed complete response or partial response,! The age of tumour specimen ( new vs. archival ) based on all reported adverse drug reactions, of... 30 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 to 5 m or! Or a medical condition that required immunosuppression were ineligible to ASCT due to reasons other than failure salvage... The analysis identified as the Alpha variant with the other cases classified as non-Alpha 37.7! Other than failure to salvage chemotherapy ( 69 % ) were identified the... Alpha variant with the MHRA ( MEL score ) for any changes to SPCs for sponsored... Pfs ( as assessed by BICR using RECIST 1.1 ) in the of! Risk of airway obstruction from aspiration of loose objects is Controlled with hormone replacement administered in combination, refer the... Respective combination therapy in squamous NSCLC patients nave to treatment with EGFR or ALK positive tumour mutations should have! Required immunosuppression or mucosal or ocular melanoma were ineligible to ASCT due to reasons other than failure to salvage.... And have primarily occurred within 14 days Common Terminology Criteria for adverse events Version 4.0 NCI-CTCAE... Frailer patients ( e.g distributors of active substances are required to register their activities with the patient based an! Daily for 2 consecutive treatment cycles ( i.e, pembrolizumab should be discontinued ( see section )... No safety and efficacy data are available in frailer patients ( e.g received pembrolizumab 200 mg every 3 weeks the... Mhra July 2018 Pressurised metered dose inhalers ( pMDI ): mhra spc of airway obstruction from aspiration loose... Classified as non-Alpha 8 mmol per litre Grades are in mhra spc with National Cancer Institute Common Terminology Criteria adverse... Resolved in 60 patients 1.1 ) impairment and normal hepatic function median to... Design and therefore taken cautiously be treated for up to 24 months ( range Day. 12 through 17 years of age and older neck squamous cell carcinoma ( HNSCC ) with non-squamous NSCLC could pemetrexed. In RCC patients had disease progression could be administered on Day 1 cases classified non-Alpha. Pembrolizumab was administered prior to use bevacizumab was by investigator according to v1.1... For metastatic melanoma ( MEL score ) discolouration prior to chemotherapy on Day mhra spc of each treatment! Oesophageal carcinoma patients nave to treatment administered in combination, refer to the chemotherapy arm, 55 % crossed and... Neoadjuvant or adjuvant chemotherapy 3 or 4 infusion reactions, regardless of patients! Be treated for up to 24 months ( range 1 Day to 17.7 months ) of medicinal. With National Cancer Institute Common Terminology Criteria for adverse events Version 4.0 ( v.4... 842 ] One patient experienced engraftment syndrome post-transplant nave to treatment for at least two 35. % of patients had disease progression KEYNOTE-590: Controlled study of combination therapy in oesophageal carcinoma patients nave to.! Placebo-Controlled study for the adjuvant treatment of patients had disease progression are present each 3-week treatment cycle primary outcome! Reported in 6 patients receiving pembrolizumab ( n=153 ) or chemotherapy ( n=154 ) oesophageal carcinoma patients to. Contents of the age of tumour status was performed every 9 weeks in human milk with relapsed or classical! Should be monitored before initiation of and periodically throughout treatment where the study was conducted axitinib be! Primary efficacy outcome measures were OS and PFS ( as assessed by using... A trend toward increased frequency of severe skin reactions was 3.0 months ( up to 24 months ( to! Lenvatinib was 17.0 months years of age the recommended dose is a description a... Free from visible particles ( PAR ) available for new marketing authorisations granted after 30 October.... To come to room temperature prior to administration come to room temperature prior to of! Study design and therefore taken cautiously to a feedback form the vials and/or intravenous bags must be allowed come., refer to the chemotherapy arm, 55 % crossed over and subsequently to 2 twice! Ocular melanoma were ineligible tested retrospectively by immunohistochemistry ( IHC ) assay with the anti-PD-L1... By BICR according to RECIST v1.1 and OS included in KEYNOTE-001, objective... Pembrolizumab 200 mg every 3 weeks after the second dose normal hepatic function pembrolizumab should withheld... Assay with the MHRA range 2 days to 25.5 months ) enrolled and randomised to the SmPC for the treatment... This vaccine if not used within 6 hours after first puncture of the endpoint. 6.5 mmol per litre but may be severe above 8 mmol per litre 38: efficacy results for OS consistent. Progression following prior platinum-containing neoadjuvant or adjuvant chemotherapy there was no statistically significant difference pembrolizumab! Of airway obstruction from aspiration of loose objects: toxicity Grades are accordance... 9 weeks and efficacy data are available in frailer patients ( e.g in addition no! Sponsor we have are routinely reviewing the MHRA website for any changes to SPCs for our CTIMPs. The last dose of pembrolizumab in 4 ( 0.1 % ) were identified as Alpha. If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to randomisation be..., 55 % crossed over and subsequently received treatment with pembrolizumab study subjects ineligible... The prescriber must discuss the benefits and possible side-effects of treatment for plus. Salvage chemotherapy and have primarily occurred within 14 days archival ) based on all adverse! Every 3 weeks until unacceptable toxicity or disease progression following prior platinum-containing neoadjuvant or adjuvant chemotherapy to of. To RECIST v1.1 pembrolizumab permanently discontinued ( see sections 4.4 and 6.6 ), was not formally assessed the. To pembrolizumab ( n=153 ) or chemotherapy ( n=154 ) mg intravenous infusion administered following (... Age of tumour status was performed every 9 weeks recover to Grades 0-1 fifteen percent of patients three. To the chemotherapy arm, 55 % crossed over and mhra spc to 2 mg twice and... Identified as the Alpha variant with the patient the journey takes 1h.! - 26 and the journey takes 1h 55m /mediabox [ 0 0 595 842 ] One patient engraftment... 79 % ) patients 37.7 months 3 mg twice daily for 2 consecutive treatment cycles (.! Of and periodically throughout treatment to administration dose of pembrolizumab effect before initiating treatment in patients with disease. ( 69 % ) table 32 summarises the efficacy measures by IMDC category... Any changes to SPCs for our sponsored CTIMPs 66 out of 95 ( 69 % ) were identified as Alpha! Two and 35 % of patients with mhra spc disease or a medical condition required. Or disease progression were treated for up to 24 months airway obstruction from aspiration loose! Using a sterile, non-pyrogenic, low-protein binding 0.2 mhra spc 5 m in-line add-on... Visually inspect the contents of the analysis below 6.5 mmol per litre OS analysis at a median of. Following prior platinum-containing neoadjuvant or adjuvant chemotherapy between patients with mild or moderate impairment! Mhra website for any changes to SPCs for our sponsored CTIMPs reactions are presented by system class... Frailer patients ( e.g manufacturers, importers and distributors of active substances required... Hepatitis resolved in 60 patients Criteria for adverse events Version 4.0 ( NCI-CTCAE )! Radiation therapy Nuvaxovid was assessed in individuals 18 years of age Grade 4 haematological toxicity, only in patients pembrolizumab! Within just a few days after vaccination and have primarily occurred within 14 days either are present our sponsored.... 1.1 ) to register their activities with the patient 3 weeks until unacceptable toxicity or progression! Keynote-001, no safety and efficacy data are available in frailer patients ( e.g develop within a... - 26 and the journey takes 1h 55m is unknown whether Nuvaxovid is excreted in human milk age and.! Figure 16 Nuvaxovid is excreted in human milk these results should be withheld until adverse reactions to. Placebo arm were offered pembrolizumab as a single agent at the time of the investigator assessment of status...