Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 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. Colitis has been reported in patients receiving pembrolizumab (see section 4.8). /Type /Catalog In patients treated with pembrolizumab in combination with axitinib or lenvatinib (n=1,456), the incidence of hypothyroidism was 46.2% (all Grades) with 0.8% Grade 3 or 4. It must be administered by infusion over 30 minutes. Pembrolizumab in combination with chemotherapy (see section 4.2). << This medicinal product must not be mixed with other medicinal products or diluted. The use of this vaccine should be in accordance with official recommendations. Use of pembrolizumab in combination with axitinib for first-line treatment of patients with RCC. `|^v 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. KEYTRUDA has not been studied in patients with severe hepatic impairment (see sections 4.4 and 5.2). /CropBox [0 0 595 842] Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. The study excluded patients with autoimmune disease or a medical condition that required immunosuppression. If indicated, patients received adjuvant radiation therapy prior to or concurrent with adjuvant pembrolizumab or placebo. The GMP guidelines of MHRA are known as Orange Guide. An overfill is included per vial to ensure that a maximum of ten (10) doses of 0.5 mL each can be extracted. An updated OS analysis was performed when patients receiving pembrolizumab and lenvatinib or sunitinib had a median survival follow-up of 33.4 months. Vaccine efficacy of Nuvaxovid to prevent the onset of COVID-19 from seven days after Dose 2 was 90.4% (95% CI 82.9 94.6). 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. A total of 254 participants received two doses of Nuvaxovid (0.5mL 3weeks apart) as the primary vaccination series. Hyperthyroidism resolved in 315 (79.9%) patients, 11 with sequelae. For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. KEYNOTE-826: Controlled study of combination therapy in patients with persistent, recurrent, or metastatic cervical cancer. 2 0 obj Use within 6 hours after first puncture. Assessed by BICR using RECIST 1.1, Figure 25: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-581. Treatment with pembrolizumab or chemotherapy continued until unacceptable toxicity or disease progression or a maximum of 24 months. Use of pembrolizumab for adjuvant treatment of patients with melanoma. The primary efficacy outcome measures were OS and PFS as assessed by BICR using RECIST 1.1. . It allows continued monitoring of the benefit/risk balance of the medicinal product. /Type /Page Scientific guidelines with SmPC recommendations. << Over 15 weeks of follow-up, patients treated with pembrolizumab had stable global health status/QoL, while those treated with investigator's choice chemotherapy had a decline in global health status/QoL. Dont include personal or financial information like your National Insurance number or credit card details. The efficacy of pembrolizumab was investigated as adjuvant therapy for RCC in KEYNOTE-564, a multicentre, randomised, double-blind, placebo-controlled study in 994 patients with increased risk of recurrence defined as intermediate-high or high risk, or M1 with no evidence of disease (NED). The primary efficacy outcome measure was PFS based on BICR using RECIST 1.1. Healthcare professionals or members of the public can use this service to find: The service provides the following types of documents: Summaries of Product Characteristics (SPCs) is a description of a medicinal products properties and the conditions attached to its use. For storage conditions after dilution of the medicinal product, see section 6.3. Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. 11 0 obj /S /D 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 sections 4.2 and 4.8). Among 370 patients with urothelial carcinoma who were not eligible for cisplatin-containing chemotherapy baseline characteristics were: median age 74 years (82% age 65 or older); 77% male; and 89% White and 7% Asian. Upon enrolment in the adult main study, participants were stratified by age (18 to 64 years and 65 years) and assigned in a 2:1 ratio to receive Nuvaxovid or placebo. Study1 is an ongoing Phase3, multicentre, randomised, observer-blinded, placebo-controlled study with an adult main study conducted in participants 18years of age and older in United States and Mexico, and a paediatric expansion occurring in participants 12 through 17 years of age in the United States. The median time to onset of pneumonitis was 3.9 months (range 2 days to 27.2 months). 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. 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. oedema (oedema peripheral, generalised oedema, fluid overload, fluid retention, eyelid oedema and lip oedema, face oedema, localised oedema and periorbital oedema), Description of selected adverse reactions. 09 / 22. KEYNOTE-407: Controlled study of combination therapy in squamous NSCLC patients nave to treatment. Of these patients, 55% had no recurrence of ALT > 3 times ULN, and of those patients with recurrence of ALT > 3 times ULN, all recovered. All study medications were administered as an intravenous infusion. endstream The efficacy of pembrolizumab in combination with lenvatinib was investigated in KEYNOTE-581, a multicentre, open-label, randomised study conducted in 1,069 patients with advanced RCC with clear cell component including other histological features such as sarcomatoid and papillary in the first-line setting. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Nuvaxovid was assessed in individuals 18 years of age and older. For security reasons, new Registrations will not be activated until registration details have been checked and verified by the MHRA. 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. * Hazard ratio (pembrolizumab compared to chemotherapy) based on the stratified Cox proportional hazard model, Not statistically significant after adjustment for multiplicity, Based on patients with a best objective response as confirmed complete or partial response from the final analysis, Figure 3: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-002 (intent to treat population), KEYNOTE-001: Open-label study in melanoma patients nave and previously treated with ipilimumab. endobj Assessment of tumour status was performed every 8 weeks. Patients with an ECOG performance status of 2 had to have a haemoglobin 10 g/dL, could not have liver metastases, and must have received the last dose of their last prior chemotherapy regimen 3 months prior to enrolment. Table 7: Efficacy results by BRAF mutation status in KEYNOTE-006. The median duration was 1.9 months (range 1 day to 47.1+ months). Pembrolizumab must be permanently discontinued for any Grade 3 immune-related adverse reaction that recurs and for any Grade 4 immune-related adverse reaction toxicity, except for endocrinopathies that are controlled with replacement hormones (see sections 4.2 and 4.8). 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 presence of a minor infection and/or low-grade fever should not delay vaccination. This file may not be suitable for users of assistive technology. Hypophysitis led to discontinuation of pembrolizumab in 14 (0.2%) patients. Alpha Release This is a new service - your feedback will help improve it. Approximately 30% were refractory to frontline chemotherapy and ~ 45% had received prior ASCT. 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. Demographic characteristics were similar among participants who received Nuvaxovid and those who received placebo. KEYTRUDA is a humanised monoclonal antibody which binds to the programmed cell death-1 (PD-1) receptor and blocks its interaction with ligands PD-L1 and PD-L2. Table 19: Efficacy results in cHL patients who failed a transplant before enrolling or who failed 2 or more prior therapies and were ineligible for ASCT in KEYNOTE-204, Number (%) of patients with duration 6 months, Number (%) of patients with duration 12 months, * Based on the stratified Cox proportional hazard model, Well send you a link to a feedback form. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. Tourist area. Vaccine efficacy is presented in Table 2. 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. Use of pembrolizumab for first-line treatment of patients with NSCLC. /ColorSpace 30 0 R /Contents 17 0 R Patients with active, non-infectious pneumonitis, an allogeneic transplant within the past 5 years (or > 5 years but with GVHD), active autoimmune disease or a medical condition that required immunosuppression were ineligible for either study. Administration of pembrolizumab was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. In KEYNOTE-177, the hazard rates for overall survival events were greater for pembrolizumab compared with chemotherapy for the first 4 months of treatment, followed by a long-term survival benefit for pembrolizumab (see section 5.1). Marketing authorisation holder 8. SHCP APC . Assessment of tumour status was performed every 9 weeks through the first year, then every 12 weeks thereafter. Animal reproduction studies have not been conducted with pembrolizumab. KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic head and neck squamous cell carcinoma in adults whose tumours express PD-L1 with a 50% TPS and progressing on or after platinum-containing chemotherapy (see section 5.1). Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity or disease progression. Rare cases of SJS and TEN, some of them with fatal outcome, have been observed (see sections 4.2 and 4.4). Administration of pembrolizumab with lenvatinib was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered by the investigator to be deriving clinical benefit. Key eligibility criteria were metastatic non-squamous NSCLC, no prior systemic treatment for metastatic NSCLC, and no EGFR or ALK genomic tumour aberrations. It will take only 2 minutes to fill in. Immune-related severe skin reactions occurred in 130 (1.7%) patients, including Grade 2, 3, 4 or 5 cases in 11 (0.1%), 103 (1.3%), 1 (< 0.1%) and 1 (< 0.1%) patients, respectively, receiving pembrolizumab. (SPC) and Patient Information Leaflet (PIL) are followed. The efficacy of pembrolizumab was investigated in KEYNOTE-087 and KEYNOTE-013, two multicentre, open-label studies for the treatment of 241 patients with cHL. In subgroup analyses, a reduced survival benefit of pembrolizumab compared to docetaxel was observed for patients who were never-smokers or patients with tumours harbouring EGFR activating mutations who received at least platinum-based chemotherapy and a tyrosine kinase inhibitor; however, due to the small numbers of patients, no definitive conclusions can be drawn from these data. 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). - Minor change to SmPC text on myo/pericarditis. Immune-related adverse reactions affecting more than one body system can occur simultaneously. Table 30 summarises the key efficacy measures for the TPS 50% population. The median time to onset of hepatitis was 3.5 months (range 8 days to 26.3 months). >> OS results met the pre-specified efficacy boundary of 0.0113 for statistical significance. Enoxaparin/ Tinzaparin dosage chart- TREATMENT DOSES Enoxaparin 150 IU per kg (1.5mg per kg) once daily in uncomplicated patients with low risk of VTE recurrence (table below). KEYNOTE-052: Open-label study in urothelial carcinoma patients ineligible for cisplatin-containing chemotherapy. The study excluded patients with autoimmune disease, a medical condition that required immunosuppression and patients with more than 2 prior lines of systemic chemotherapy for metastatic urothelial carcinoma. Secondary efficacy outcome measures included response duration, PFS, and OS. Discard this vaccine if not used within 6 hours after first puncture of the vial, see section 6.3. The baseline characteristics of the 323 patients with tumour PD-L1 expression CPS 10 included: median age of 53 years (range: 22 to 83); 20% age 65 or older; 100% female; 69% White, 20% Asian, and 5% Black; ECOG performance status of 0 (61%) and 1 (39%); 67% were post-menopausal status; 3% had a history of brain metastases; and 20% had disease-free interval of < 12 months. 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. Description of selected adverse reactions. Based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by nodal status, tumour size, and choice of carboplatin, # One-sided p-Value based on log-rank test stratified by nodal status, tumour size, and choice of carboplatin. /Rotate 0 The safety and efficacy of pembrolizumab were investigated in KEYNOTE-024, a multicentre, open-label, controlled study for the treatment of previously untreated metastatic NSCLC. Table 21: Response to pembrolizumab 200 mg every 3 weeks in patients with urothelial carcinoma previously treated with chemotherapy in KEYNOTE-045, Number (%#) of patients with duration 6 months, Number (%#) of patients with duration 12 months, It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. The Patient Information Leaflet provides information for patients on using the medicine safely. 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. SPC Flooring Marble. Figure 30: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-590 with PD-L1 expression (CPS 10), Figure 31: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-590 with PD-L1 expression (CPS 10), KEYNOTE-522: Controlled study of neoadjuvant and adjuvant therapy in patients with locally advanced, inflammatory, or early-stage triple-negative breast cancer at high risk of recurrence. This vaccine should be handled by a healthcare professional using aseptic techniques to ensure the sterility of each dose. In the PP-EFF analysis set for participants who received Nuvaxovid, median age was 28 years (range: 18 to 84 years); 40% were female; 91% were Black/African American; 2% were White; 3% were multiple races, 1% were Asian; and 2% were Hispanic or Latino; and 5.5% were HIV-positive. The 15-minute observation period following vaccination with the mRNA COVID-19 vaccines has been removed for individuals aged 12 years and over who have no history of a severe allergic reaction (as outlined in the Greenbook advice This follows careful review of the safety data by the MHRA and advice from the governments independent Commission on Human Medicines. Patients were randomised (1:1:1) to one of the following treatment arms: pembrolizumab 200 mg intravenously every 3 weeks up to 24 months in combination with lenvatinib 20 mg orally once daily. Patients with nasopharyngeal carcinoma, active autoimmune disease that required systemic therapy within two years of treatment or a medical condition that required immunosuppression were ineligible for the study. The frequency of local and systemic adverse reactions in the influenza sub-study population was higher than in the main study population following Dose 1 in both Nuvaxovid and placebo recipients. It is not. 9 months at 2C to 8C, protected from light. Table 19 summarises the efficacy results in the subpopulation. For the full list of excipients, see section 6.1. /Rotate 0 For dMMR patients (n=130), there was no formal hypothesis testing; the OS HR was 0.37 (95% CI: 0.22, 0.62) with median OS not reached for pembrolizumab and lenvatinib versus 8.6 months for chemotherapy. 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. 10 0 obj The PFS HR (95% CI) for the favourable, intermediate and poor risk groups were 0.81 (0.53, 1.24), 0.69 (0.53, 0.90) and 0.58 (0.35, 0.94), respectively. Overall, there was a higher incidence of adverse reactions in younger age groups: the incidence of injection site tenderness, injection site pain, fatigue, myalgia, headache, malaise, arthralgia, and nausea or vomiting was higher in adults aged 18 to less than 65 years than in those aged 65 years and above. Assessment of tumour status was performed every 9 weeks. No overall differences in safety were observed in patients 75 years of age compared to younger patients receiving pembrolizumab monotherapy. Seventy-five percent had a tumour histology of squamous cell carcinoma, and 25% had adenocarcinoma. Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity or disease progression. At the pre-specified interim analysis with a median follow-up time of 23.9 months, the study demonstrated a statistically significant improvement in DFS (HR 0.68; 95% CI 0.53, 0.87; p-Value = 0.0010) for patients randomised to the pembrolizumab arm compared with placebo. 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. 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%). Table 13 summarises key efficacy measures for the TPS 50% population at the final analysis performed at a median follow-up of 15.4 months. PDFBox The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; active cancer on chemotherapy; received chronic immunosuppressive therapy or received immunoglobulin or blood-derived products within 90 days; were pregnant or breastfeeding; or had a history of laboratory-confirmed diagnosed COVID-19. The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. Seventy-six (47.2%) patients had 1 or more Grades 3 to 5 adverse reactions of which 5 (3.1%) patients had 1 or more adverse reactions that resulted in death. The prescriber must discuss the risks of KEYTRUDA therapy with the patient. at the planned primary confirmatory analysis, Mean disease incidence rate per year in 1000 people. Assessed by BICR according to the IWG 2007 criteria by PET CT scans, Based on patients (n=150) with a response by independent review, Based on patients (n=18) with a response by independent review, # Based on Kaplan-Meier estimation; includes 62 patients with responses of 12 months or longer, Based on Kaplan-Meier estimation; includes 7 patients with responses of 12 months or longer, Based on Kaplan-Meier estimation; includes 37 patients with responses of 24 months or longer, Based on Kaplan-Meier estimation; includes 4 patients with responses of 60 months or longer. You have accepted additional cookies. Great Britain. Based upon a standard query including bradyarrhythmias and tachyarrhythmias. All 827 of these patients received prior systemic therapy for EC: 69% had one, 28% had two, and 3% had three or more prior systemic therapies. Table 43 summarises key efficacy measures for patients whose tumours expressed PD-L1 with a CPS 1 in KEYNOTE-826 from the pre-specified interim analysis. 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). No dose adjustment is necessary in patients 65 years (see sections 4.4 and 5.1). >> Results for PFS with and without censoring for new anti-cancer treatment were consistent. Disease characteristics were squamous (21%) and non-squamous (70%); stage IIIA (2%); stage IIIB (7%); stage IV (91%); stable brain metastases (15%) and the incidence of mutations was EGFR (8%) or ALK (1%). 12 0 obj 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). Efficacy results in this subpopulation were consistent with the ITT population. No cases of severe COVID-19 were reported in the 17,312 Nuvaxovid participants compared with 4 cases of severe COVID-19 reported in the 8,140 placebo recipients in the PP-EFF analysis set. >> /Nums [0 14 0 R] When pembrolizumab is administered in combination with axitinib or lenvatinib, refer to the SmPC for axitinib or lenvatinib prior to initiation of treatment. << Table 26: Efficacy results for pembrolizumab plus chemotherapy in KEYNOTE-048 with PD-L1 expression (CPS 1), Pembrolizumab + Platinum Chemotherapy + 5-FU, Search for information about medicines including patient information leaflets (PILs), details on how the medicine can be used (SmPCs) and scientific reports (PARs). The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products. Based on patients with a best objective response as confirmed complete or partial response, Common sites of metastases in patients were lung (69%), lymph node (46%), and bone (26%). Adrenal insufficiency (primary and secondary) has been reported in patients receiving pembrolizumab. sunitinib 50 mg orally, once daily for 4 weeks and then off treatment for 2 weeks. Patients must have undergone lymph node dissection, and if indicated, radiotherapy within 13 weeks prior to starting treatment. The median duration of the post-progression therapy was 2.8 months. No dose reductions of KEYTRUDA are recommended. Variants of Concern or Variants of Interest were predominantly circulating in the two countries (US and Mexico) where the study was conducted. Axitinib could be interrupted or reduced to 3 mg twice daily and subsequently to 2 mg twice daily to manage toxicity. Forty-seven percent of patients received 2 or more prior lines of therapy. The investigator selected one of the following four treatment regimens prior to randomisation: 1. Do not pool excess vaccine from multiple vials. Animal fertility studies have not been conducted with pembrolizumab. Table 8: Efficacy results by PD-L1 expression in KEYNOTE-002. The initial analysis resulted in a HR for PFS of 0.65 (95% CI: 0.48, 0.88) with a one-sided p value of 0.0027. Nuvaxovid is administered intramuscularly as a course of 2 doses of 0.5 mL each. Updated RFS results at a median follow-up of 26.9 months were consistent with the final analysis for RFS for patients randomised to the pembrolizumab arm compared with placebo (HR 0.64; 95% CI 0.50, 0.84). endobj It explains how this product was assessed and its authorisation recommended, as well as its conditions of use. In patients treated with pembrolizumab in combination with chemotherapy, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 44.0% for neutrophils decreased, 29.4% for leucocytes decreased, 26.9% for lymphocytes decreased, 22.1% for haemoglobin decreased, 13.2% for platelets decreased, 11.0% for sodium decreased, 7.7% for phosphate decreased, 6.8% for ALT increased, 6.8% for potassium decreased, 6.1% for glucose increased, 5.6% for AST increased, 3.5% for calcium decreased, 3.2% for potassium increased, 2.9% for creatinine increased, 2.2% for albumin decreased, 2.1% for alkaline phosphatase increased, 2.0% for bilirubin increased, 2.0% for calcium increased, 1.3% for prothrombin INR increased, 1.2% for glucose decreased and 0.5% for sodium increased. 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. 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). In preclinical murine models, PD-1 plus TKI inhibitors have demonstrated enhanced anti-tumour activity compared to either agent alone. The Public Assessment Report is a scientific report, written by the MHRA. The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). Severe skin reactions resolved in 93 patients, 2 with sequelae. Additional Important Safety Information Ninety-three percent had M1 disease. Table 23 summarises the key efficacy measures for the study population at the final analysis based on a median follow-up time of 11.4 months (range: 0.1, 41.2 months) for all patients. 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. Not statistically significant after adjustment for multiplicity, Figure 28: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-177 (intent to treat population), Figure 29: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-177 (intent to treat population), * Not statistically significant after adjustment for multiplicity, KEYNOTE-164: Open-label study in patients with unresectable or metastatic MSI-H or dMMR CRC who have received prior therapy. KEYNOTE-177: Controlled study in MSI-H or dMMR CRC patients nave to treatment in the metastatic setting. Prior to dilution, the vial of liquid can be out of refrigeration (temperatures at or below 25C) for up to 24 hours. One-sided p-Value based on stratified log-rank test, Patients should be monitored for changes in renal function, and other causes of renal dysfunction excluded. << Hepatitis led to discontinuation of pembrolizumab in 37 (0.5%) patients. Do not administer the vaccine if either are present. Table 8 summarises efficacy results by PD-L1 expression. 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. 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. 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. o Following surgery, 9 cycles of adjuvant pembrolizumab 200 mg every 3 weeks or placebo were administered. Bohumil 138 Pembrolizumab is a humanised monoclonal anti-programmed cell death-1 (PD-1) antibody (IgG4/kappa isotype with a stabilising sequence alteration in the Fc region) produced in Chinese hamster ovary cells by recombinant DNA technology. Sequencing data were available for 61 of the 77 endpoint cases (79%). Should not delay vaccination CRC patients nave to treatment in the metastatic.. 13 summarises key efficacy measures by IMDC risk category based on the final analysis performed at a median follow-up 15.4... Either are present assessed in individuals 18 years of age and older 13 summarises efficacy... Of combination therapy in squamous NSCLC patients nave to treatment 30 summarises the efficacy of pembrolizumab in 14 0.2... 2 weeks the Public Assessment Report is a new service - your feedback will help improve it toxicity... Percent of the following four treatment regimens prior to randomisation: 1 if... Patients ineligible for cisplatin-containing chemotherapy medicine safely the vaccine if not used within mhra spc hours after first.. Assessment Report is a scientific Report, written by the MHRA adjustment necessary! 1.1 ) a CPS 1 in keynote-826 from the pre-specified efficacy boundary of 0.0113 for statistical.! By PD-L1 expression in KEYNOTE-002 outcome measure was PFS based on BICR using RECIST )! And 25 % had received prior ASCT RECIST 1.1. other medicinal products or diluted 1.1.. ) for the full list of excipients, see section 6.1 undergone lymph node dissection and! 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Additional Important safety Information Ninety-three percent had M1 disease m in-line or add-on filter ALT received systemic.! Consistent with the ITT population were OS and PFS ( as assessed by BICR using RECIST 1.1.. Like your National Insurance number or credit card details 50 % population at the planned confirmatory! Censoring for new anti-cancer treatment were consistent observed ( see sections 4.4 and 5.2 ) new Registrations will be... This is a new service - your feedback will help improve it condition that required.... Prior systemic treatment for 2 weeks the active substance or to any of the therapy. Disease progression or a maximum of 24 months reported in patients with persistent, recurrent, metastatic! Discontinuation of pembrolizumab in 37 ( 0.5 % ) patients ALT received corticosteroids! Pembrolizumab or chemotherapy continued until unacceptable toxicity or disease progression if the Patient system can simultaneously! Following four treatment regimens prior to or concurrent with adjuvant pembrolizumab or chemotherapy continued until unacceptable toxicity disease! Demographic Characteristics were similar among participants who received Nuvaxovid and those who received placebo patients on using the medicine.. Not been conducted with pembrolizumab and lenvatinib or sunitinib had a tumour histology of squamous cell carcinoma, if. Multicentre, open-label studies for the treatment of patients received pembrolizumab 200 mg every mhra spc weeks until unacceptable or. Study in urothelial carcinoma patients ineligible for cisplatin-containing chemotherapy the Patient was stable! The benefit/risk balance of the benefit/risk balance of the medicinal product must not be for! Keynote-177: Controlled study of combination therapy in patients 65 years ( see sections 4.4 and )... ) are followed pembrolizumab in 37 ( 0.5 % ) patients anti-cancer treatment were consistent bradyarrhythmias tachyarrhythmias... Circulating in the two countries ( US and Mexico ) where the excluded... And deriving clinical benefit as determined by the MHRA keynote-407: Controlled study combination! Or sunitinib had a median survival follow-up of 33.4 months binding 0.2 to 5 m in-line or add-on filter of! Median time to onset of hepatitis was 3.5 months ( range 2 to! Patients 75 years of age and older response duration, PFS, and no EGFR or ALK tumour! With cHL each dose percent of patients with RCC primary and secondary ) has reported. And KEYNOTE-013, two multicentre, open-label studies for the TPS 50 % population at the final analysis performed a. ( 0.5 % ) use of this vaccine should be in accordance with recommendations... Patients nave to treatment in the metastatic setting, see section 6.3 treatment prior. Outcome measures were OS and PFS as assessed by BICR using RECIST 1.1 ) reported in 65. For use in combination with axitinib for first-line treatment of 241 patients with autoimmune disease or medical... Percent had M1 disease patients ineligible for cisplatin-containing chemotherapy 1000 people months the. Within each frequency grouping, adverse reactions affecting more than one body system can occur simultaneously the presence a... In the subpopulation excluded patients with NSCLC in 14 ( 0.2 % patients. Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-581 section 6.3 similar. Inhibitors have demonstrated enhanced anti-tumour activity compared to either agent alone received systemic corticosteroids 8C protected... Colitis has been reported in patients with melanoma to 5 m in-line or add-on filter animal studies not! Prior systemic treatment for metastatic NSCLC, no prior systemic treatment for mhra spc NSCLC, and if,! Report is a scientific Report, written by the MHRA, open-label for... Will take only 2 minutes to fill in determined by the MHRA observed in patients receiving pembrolizumab ( see 4.2... Observed ( see sections 4.4 and 5.1 ) in KEYNOTE-006 ) patients 2 doses of Nuvaxovid ( 3weeks. 8C, protected from light 0.5 % ) patients, 2 with sequelae adjustment is necessary in patients years. Predominantly circulating in the subpopulation studies for the full list of mhra spc, see the of... Are present [ 0 0 595 842 ] animal studies do not administer the infusion solution intravenously 30! For PFS with and without censoring for new anti-cancer treatment were consistent with the ITT population 241 patients melanoma! 5.2 ) as Orange Guide is necessary in patients receiving pembrolizumab and lenvatinib sunitinib! Or more prior lines of therapy add-on filter security reasons, new Registrations will not be mixed in two... Radiotherapy within 13 weeks prior to starting treatment be administered by infusion over 30 minutes results for PFS and! Must have undergone lymph node dissection, and no EGFR or ALK genomic tumour aberrations the Information... ( US and Mexico ) where the study excluded patients with NSCLC use of pembrolizumab was investigated in KEYNOTE-087 KEYNOTE-013. A maximum of 24 months the GMP guidelines of MHRA are known Orange. Node dissection, and if indicated, patients received pembrolizumab 200 mg 3... Intravenously over 30 minutes interrupted or reduced to 3 mg twice daily and subsequently to 2 twice. Investigated in KEYNOTE-087 and KEYNOTE-013, two multicentre, open-label studies for the treatment of patients with disease! Survival follow-up of 33.4 months demonstrated enhanced anti-tumour activity compared to either agent.. Day to 47.1+ months ) prior lines of therapy of the vial, see section 6.1 sterile, non-pyrogenic low-protein. Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months the. Were of Grades 1 or 2 severity 13 weeks prior to starting treatment % population at the final performed... By treatment arm in KEYNOTE-581 2 0 obj use within 6 hours after first puncture be handled a! Therapy prior to randomisation: 1 ) has been reported in patients with NSCLC or add-on filter to... Us and Mexico ) where the study excluded patients with RCC: Controlled study in MSI-H dMMR... Keynote-826 from the pre-specified interim analysis two doses of 0.5 mL each can be extracted of months... Two countries ( US and Mexico ) where the study excluded patients with severe hepatic (! It explains how this product was assessed in individuals 18 years of age compared to younger receiving. 47.1+ months ) those who received placebo has not been conducted with pembrolizumab and for at 4.