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. Among patients who were evaluable for PD-L1 expression (79%), 69% (n=294) were PD-L1 positive and 31% (n=134) were PD-L1 negative. Table 16 summarises key efficacy measures and Figures 13 and 14 show the Kaplan-Meier curves for OS and PFS based on the final analysis with a median follow-up of 14.3 months. DMFS results are reported from the interim analysis for DMFS at a median follow-up of 26.9 months in Table 10 and Figure 5. Date of first authorisation: 1 January 2021. Patients were randomised (1:1) to one of the following treatment arms: Pembrolizumab 200 mg 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. Store the opened vial between 2C to 25C for up to 6 hours after first puncture, see section 6.3. To help us improve GOV.UK, wed like to know more about your visit today. BRAF mutations were reported in 302 (36%) patients. Of the 89 patients receiving 2 mg/kg bw of pembrolizumab who were previously treated with ipilimumab, 53% were male, 33% were 65 years of age and the median age was 59 years (range 18-88). Factors associated with early deaths were fast progressive disease on prior platinum therapy and liver metastases. Since pembrolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected. EVUSHELD is indicated for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19 (see sections 4.2, 5.1 and 5.2).. *. Patients must have undergone lymph node dissection, and if indicated, radiotherapy within 13 weeks prior to starting treatment. The primary efficacy outcome measure was OS. It is unknown whether pembrolizumab is secreted in human milk. >> Thirty-five percent had tumour PD-L1 expression TPS < 1% [negative]; 19% were East Asian; and 60% received paclitaxel. Patients underwent imaging every 12 weeks after the first dose of pembrolizumab for the first two years, then every 6 months from year 3 to 5, and then annually. endobj Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; GMR = ratio of GMT, which is defined as the ratio of 2 GMTs for comparison of 2age cohorts; GMT = geometric mean titer; LLOQ = lower limit of quantitation; MN = microneutralisation; N = number of participants in assay-specific PP-IMM Analysis Set in each part of study with non-missing response at each visit; PP-IMM = Per-Protocol Immunogenicity; SARS-CoV-2 = severe acute respiratory syndrome coronavirus2. 09/24. endobj The study demonstrated statistically significant improvements in OS and ORR for patients randomised to pembrolizumab as compared to chemotherapy. Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates for male and female participants and racial groups, and across participants with medical comorbidities associated with high risk of severe COVID-19. The information for healthcare professionals and UK recipients on using the bivalent vaccine safely will be periodically updated as new data become available. Table 31: Efficacy results in KEYNOTE-426, Number (%#) of patients with duration 30 months, Use of pembrolizumab in urothelial carcinoma patients who have received prior platinum-containing chemotherapy. Data were available for 95 of the 106 endpoint cases (90%). At least one pre-existing comorbidity or lifestyle characteristic associated with an increased risk of severe COVID-19 was present in 16,493 (95%) participants. Patients who experienced GVHD after their transplant procedure may be at an increased risk for GVHD after treatment with pembrolizumab. Enrolment of adolescents completed in June 2021. A total of 1,019 adult patients were randomised (1:1) to receive pembrolizumab 200 mg every three weeks (n=514) or placebo (n=505), for up to one year until disease recurrence or unacceptable toxicity. Objective responses were observed regardless of BRAF or RAS mutation status. The two vaccine components elicit B- and T-cell immune responses to the S protein, including neutralising antibodies, which may contribute to protection against COVID-19. The efficacy, safety, and immunogenicity of the vaccine has been assessed in a limited number of immunocompromised individuals. Pembrolizumab CL is approximately 23% lower (geometric mean, 195 mL/day [CV%: 40%]) after achieving maximal change at steady-state compared with the first dose (252 mL/day [CV%: 37%]); this decrease in CL with time is not considered clinically meaningful. Main efficacy results are summarised in Table 20. For additional axitinib safety information for elevated liver enzymes see also section 4.4. The study demonstrated a statistically significant improvement in PFS at its pre-specified interim analysis (HR 0.65; 95% CI 0.49, 0.86; p-Value 0.0012) and OS at final analysis for patients with tumour PD-L1 expression CPS 10 randomised to the pembrolizumab in combination with chemotherapy arm compared with placebo in combination with chemotherapy. 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). Based on the severity of the adverse reaction, pembrolizumab should be withheld for Grade 3 skin reactions until recovery to Grade 1 or permanently discontinued for Grade 4 skin reactions, and corticosteroids should be administered (see section 4.2). Interpretation of HR is limited by the low number of events (24/193 and 34/193), PDFBox 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. Assessment of tumour status was performed at 12 weeks, then every 6 weeks through Week 48, followed by every 12 weeks thereafter. Renfe Viajeros operates a train from Malaga Maria Zambrano to Sevilla-Santa Justa every 4 hours. This SCA should be read in conjunction with the Summary of Product Characteristics (SPC) and the current edition of the British National Formulary . Thyroid disorders, including hypothyroidism, hyperthyroidism and thyroiditis, have been reported in patients receiving pembrolizumab and can occur at any time during treatment. We also publish Safety Public Assessment Reports, Further information about SPC, PILs and PARs, The leaflets which are provided with medicines, The description of the medicinal products properties and how it can be used, Scientific reports about marketing authorisations for medicines. The exposure multiple between the NOAEL and a human dose of 200 mg was 74. The primary efficacy outcome measures were PFS assessed by BICR according to RECIST v1.1 and OS. endstream Dont include personal or financial information like your National Insurance number or credit card details. A 30% reduction in antibody responses to Nuvaxovid was noted as assessed by an anti-spike IgG assay with seroconversion rates similar to participants who did not receive concomitant influenza vaccine (see section 4.5 and section 4.8). Microsoft Word - 1646658070014998238_spc-doc.doc This product is considered high in sodium. In these patient populations, the most frequent adverse reactions were diarrhoea (58%), hypertension (54%), hypothyroidism (46%), fatigue (41%), decreased appetite (40%), nausea (40%), arthralgia (30%), vomiting (28%), weight decreased (28%), dysphonia (28%), abdominal pain (28%), proteinuria (27%), palmar-plantar erythrodysaesthesia syndrome (26%), rash (26%), stomatitis (25%), constipation (25%), musculoskeletal pain (23%), headache (23%) and cough (21%). 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. Nuvaxovid is composed of purified full-length SARS-CoV-2 recombinant spike (S) protein that is stabilised in its prefusion conformation. The MHRA products website allows you to find: The leaflets which are provided with medicines The description of the medicinal product's properties and how it can be used Scientific reports about. Go to Products website to find information on medicines. The study demonstrated a statistically significant improvement in OS for all patients randomised to pembrolizumab in combination with chemotherapy compared to standard treatment (HR 0.72; 95% CI 0.60-0.87) and in patients whose tumours expressed PD-L1 CPS 1 randomised to pembrolizumab monotherapy compared to standard treatment. NOTE: for RCC patients treated with pembrolizumab in combination with axitinib with liver enzyme elevations, see dosing guidelines following this table. No data are available. For additional safety information when pembrolizumab is administered in combination, refer to the SmPC for the respective combination therapy components. Updated to add product information about the Moderna (Spikevax) Original/Omicron BA.4/5 vaccine. If you use assistive technology (such as a screen reader) and need a Table 39 summarises key efficacy measures from the pre-specified analysis in patients whose tumours expressed PD-L1 with a CPS 10 in KEYNOTE-590 performed at a median follow-up time of 13.5 months (range: 0.5 to 32.7 months). Seventy-six percent of patients received prior cisplatin, 23% had prior carboplatin, and 1% was treated with other platinum-based regimens. 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. The efficacy of pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel was investigated in Study KEYNOTE-407, a randomised, double-blind, multicentre, placebo-controlled study. 4 mL of concentrate in a 10 mL Type I clear glass vial, with a coated grey chlorobutyl or bromobutyl stopper and an aluminium seal with a dark blue coloured flip-off cap, containing 100 mg pembrolizumab. /Contents 27 0 R Ninety-eight percent of the patients had M1 disease and 2% had M0 disease. /Subtype /XML 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. Colitis occurred in 158 (2.1%) patients, including Grade 2, 3 or 4 cases in 49 (0.6%), 82 (1.1%) and 6 (0.1%) patients, respectively, receiving pembrolizumab. Hypothyroidism may be managed with replacement therapy without treatment interruption. 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. No. /Kids [7 0 R 8 0 R 9 0 R 10 0 R 11 0 R 12 0 R 13 0 R] Patients with Grades 1 or 2 infusion reaction may continue to receive pembrolizumab with close monitoring; premedication with antipyretic and antihistamine may be considered. Efficacy results are summarised in Table 38. Special populations Elderly No dose adjustment is required in elderly. Of 14 patients in KEYNOTE-204 who proceeded to allogeneic HSCT after treatment with pembrolizumab, 8 patients reported acute GVHD and 3 patients reported chronic GVHD, none of which were fatal. 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. Sixty-seven percent (67%) of patients had M1 disease and the majority had stage IV disease (stage IV 32%, stage IVa 14%, stage IVb 4%, and stage IVc 44%). The median time to onset of hypophysitis was 5.9 months (range 1 day to 17.7 months). Safety and immunogenicity of COVID-19 vaccines given as a third dose (booster) following completion of a primary vaccination series with another authorizsed COVID-19 vaccine in the UK. When suggestions are available use up and down arrows to review and ENTER to select. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT), Allogeneic HSCT after treatment with pembrolizumab. Participants with confirmed infection or prior infection due to SARSCoV-2 at the time of randomisation were not included in the primary efficacy analysis. Efficacy results by MSKCC prognostic group are summarised in Table 34. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of the vaccine. For liver enzyme elevations, in patients with RCC being treated with KEYTRUDA in combination with axitinib: If ALT or AST 3 times ULN but < 10 times ULN without concurrent total bilirubin 2 times ULN, both KEYTRUDA and axitinib should be withheld until these adverse reactions recover to Grades 0-1. 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