The primary efficacy outcome measures were investigator-assessed RFS in the whole population and in the population with PD-L1 positive tumours, where RFS was defined as the time between the date of randomisation and the date of first recurrence (local, regional, or distant metastasis) or death, whichever occurs first. Hypophysitis resolved in 15 patients, 8 with sequelae. Table 13: Efficacy results (PD-L1 TPS 50%) in KEYNOTE-042, Figure 10: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-042 (patients with PD-L1 expression TPS 50%, intent to treat population). 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. If not used immediately, in-use storage times and conditions are the responsibility of the user. The study demonstrated a statistically significant improvement in OS and PFS for all pre-specified study populations. 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). The relationship between body weight and clearance supports the use of either fixed dose or body weight-based dosing to provide adequate and similar control of exposure. This 96-hour hold may include up to 6 hours at room temperature (at or below 25C). Table 4 summarises key efficacy measures at the final analysis in patients previously treated with ipilimumab, and the Kaplan-Meier curve for PFS is shown in Figure 3. A Public Assessment Report (PAR) is a scientific assessment report available for marketing authorisations granted after 30 October 2005. 6472 Patients treated with pembrolizumab without disease progression could be treated for up to 24 months. If not used immediately, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at 2C to 8C. We use some essential cookies to make this website work. We use some essential cookies to make this website work. Based on best response of stable disease or better, From a microbiological point of view, the product, once diluted, should be used immediately. These results were consistent when reclassified in a post-hoc analysis according to the current AJCC 8th edition staging system. Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. In patients treated with pembrolizumab monotherapy, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 9.4% for lymphocytes decreased, 7.4% for sodium decreased, 5.8% for haemoglobin decreased, 5.3% for phosphate decreased, 5.3% for glucose increased, 3.3% for ALT increased, 3.1% for AST increased, 2.6% for alkaline phosphatase increased, 2.3% for potassium decreased, 2.1% for potassium increased, 1.9% for neutrophils decreased, 1.8% for platelets decreased, 1.8% for calcium increased, 1.7% for bilirubin increased, 1.5% for calcium decreased, 1.4% for albumin decreased, 1.3% for creatinine increased, 1.2% for glucose decreased, 0.8% for leucocytes decreased, 0.7% for magnesium increased, 0.5% for sodium increased, 0.4% for haemoglobin increased, and 0.2% for magnesium decreased. 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. Nominal p-Value based on log-rank test stratified by American Joint Committee on Cancer (AJCC) 8th edition T stage. >> For RCC patients treated with KEYTRUDA in combination with axitinib, see the SmPC regarding dosing of axitinib. Use within 6 hours after first puncture. 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. See section 4.8 for how to report adverse reactions. The same scoring system was used for metastatic melanoma (MEL score). 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). There is an increased risk of myocarditis and pericarditis following vaccination with Nuvaxovid. 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. 4.6 Fertility, Pregnancy and lactation Pregnancy Data on a limited number (242) of exposed pregnancies indicate no adverse effects of Indocyanine green on pregnancy or on the health of the Expires . The efficacy of pembrolizumab was investigated in KEYNOTE-164, a multicentre, non-randomised, open-label, multi-cohort Phase II study that enrolled patients with unresectable or metastatic MSI-H or dMMR CRC that progressed following prior fluoropyrimidine-based therapy in combination with irinotecan and/or oxaliplatin. 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. The primary efficacy outcome measures were PFS assessed by BICR according to RECIST v1.1 and OS. Based on available safety data in cHL and other tumour types, these differences are not clinically meaningful. Individuals who have received a first dose of Nuvaxovid should receive the second dose of Nuvaxovid to complete the vaccination course. Insulin should be administered for type 1 diabetes, and pembrolizumab should be withheld in cases of type 1 diabetes associated with Grade 3 hyperglycaemia or ketoacidosis until metabolic control is achieved (see section 4.2). Microsoft Word - 1646658070014998238_spc-doc.doc 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. o Followed by four additional cycles of neoadjuvant pembrolizumab 200 mg every 3 weeks or placebo on Day 1 of cycles 5-8 of treatment regimen in combination with: Doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 every 3 weeks on Day 1 of cycles 5-8 of treatment regimen and, Cyclophosphamide 600 mg/m2 every 3 weeks on Day 1 of cycles 5-8 of treatment regimen. However, some of the effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines. This is based on the MHRA assessment report with any commercially or personally confidential information removed. BRAF mutations were reported in 20 (39%) patients. Twenty-one percent had received 2 prior systemic regimens in the metastatic setting. The safety profile in paediatric patients was generally similar to that seen in adults treated with pembrolizumab. To help us improve GOV.UK, wed like to know more about your visit today. Hypophysitis has also been reported in patients receiving pembrolizumab (see section 4.8). If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to use. An ANCOVA with age cohort as main effect and baseline MN Assay neutralizing antibodies as covariate was performed to estimate the GMR. British National Formulary accessed online sept 2019 3. Patients were enrolled regardless of PD-L1 tumour expression status. HWK[%'HNR*3'9!0\BZ_~ @HR`_w?|Qw2jw3&R^E KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic non-small cell lung carcinoma in adults whose tumours express PD-L1 with a 1% TPS and who have received at least one prior chemotherapy regimen. Participants may have received up to 2 platinum-containing therapies in total, as long as one was given in the neoadjuvant or adjuvant treatment setting. For pMMR patients (n=697), the OS HR was 0.68 (95% CI: 0.56, 0.84), p=0.0001, one-sided; with median OS of 17.4 months for pembrolizumab and lenvatinib versus 12.0 months for chemotherapy. 1 0 obj The primary efficacy outcome measure was PFS as assessed by blinded independent central review (BICR) using RECIST 1.1. The efficacy of Nuvaxovid was consistent between elderly ( 65 years) and younger individuals (18 to 64 years). Based on the severity and type of the adverse reaction, pembrolizumab should be withheld for Grade 2 or Grade 3 events and corticosteroids administered. KEYNOTE-716: Placebo-controlled study for the adjuvant treatment of patients with resected Stage IIB or IIC melanoma. /Type /Page KEYTRUDA, in combination with lenvatinib, is indicated for the first-line treatment of advanced renal cell carcinoma in adults (see section 5.1). OS and PFS benefits were observed regardless of PD-L1 expression level. Based on Kaplan-Meier estimation, Figure 22: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-040 patients with PD-L1 expression (TPS 50%), KEYNOTE-426: Controlled study of combination therapy with axitinib in RCC patients nave to treatment. Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. 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. %PDF-1.4 Patients were randomised (2:1) to one of the following treatment arms via intravenous infusion: Pembrolizumab 200 mg 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. Patients were randomised (1:1) to one of the two treatment groups: Treatment Group 1: Pembrolizumab 200 mg plus chemotherapy with or without bevacizumab, Treatment Group 2: Placebo plus chemotherapy with or without bevacizumab. Nominal 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). Assessment of tumour status was performed at 9 weeks, then every 6 weeks through Week 52, followed by every 9 weeks through 24 months. /Filter /FlateDecode Patients with non-squamous NSCLC could receive pemetrexed maintenance.). Based on Kaplan-Meier estimation, Figure 18: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-361 (intent to treat population, choice of carboplatin), Figure 19: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-361 (patients with PD-L1 expression CPS 10, intent to treat population, choice of carboplatin), KEYNOTE-048: Controlled study of monotherapy and combination therapy in HNSCC patients nave to treatment in the recurrent or metastatic setting. Common sites of metastases in patients were lung (69%), lymph node (46%), and bone (26%). Table 18: Response to pembrolizumab 2 or 10 mg/kg bw every 3 weeks in previously treated patients with NSCLC in KEYNOTE-010, * Hazard ratio (pembrolizumab compared to docetaxel) based on the stratified Cox proportional hazard model, KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with renal cell carcinoma at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions (for selection criteria, please see section 5.1). 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%). 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). KEYTRUDA 25 mg/mL concentrate for solution for infusion. The median duration was not reached (range 2 days to 63.0+ months). Lenvatinib should be withheld, dose reduced, or discontinued in accordance with the instructions in the lenvatinib SmPC for combination with pembrolizumab. /Length 6 0 R It is unknown whether Nuvaxovid is excreted in human milk. KEYNOTE-052: Open-label study in urothelial carcinoma patients ineligible for cisplatin-containing chemotherapy. Neutralising antibody titers measured by a wild-type assay were assessed 28 days post-booster dose. In Study 3, an ongoing Phase 2a/b randomizsed, observer-blinded, placebo-controlled study, the safety and immunogenicity of booster dose was evaluated in healthy HIV-negative adult participants 18 to 84years of age and medically stable PLWH 18 to 64years of age who were seronegative to SARS-CoV-2 at baseline. /Parent 3 0 R 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, 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). Patients without disease progression could be treated for up to 24 months. Corticosteroids should be administered for Grade 2 events (initial dose of 1-2 mg/kg/day prednisone or equivalent followed by a taper) and, based on severity of creatinine elevations, pembrolizumab should be withheld for Grade 2, and permanently discontinued for Grade 3 or Grade 4 nephritis (see section 4.2). We use some essential cookies to make this website work. The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products. It is unknown whether pembrolizumab is secreted in human milk. Vaccinees (including parents or caregivers) should be instructed to seek immediate medical attention if they develop symptoms indicative of myocarditis or pericarditis such as (acute and persisting) chest pain, shortness of breath, or palpitations following vaccination. It is not. New information on this medicinal product will be reviewed at least every year and this SmPC will be updated as necessary. The most common adverse reactions (reported in at least 20% of paediatric patients) were pyrexia (33%), vomiting (30%), headache (26%), abdominal pain (22%), anaemia (21%), cough (21%) and constipation (20%). Such authorisations may therefore serve as the basis for SPC applications filed at the UKIPO. You have accepted additional cookies. The resultant vaccine efficacy of Nuvaxovid was 48.6% (95% CI: 28.4, 63.1). /MediaBox [0 0 595 842] 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). ) using RECIST 1.1 4.8 ) PFS assessed by BICR according to the AJCC... Medicinal product will be updated as necessary younger individuals ( 18 to 64 years.! Recist 1.1 elderly ( 65 years ) medical condition that required immunosuppression were ineligible pembrolizumab without disease progression be. 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