Use of pembrolizumab for first-line treatment of patients with HNSCC. The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products. It will take only 2 minutes to fill in. # 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. Pneumonitis led to discontinuation of pembrolizumab in 131 (1.7%) patients. Ninety percent of patients were treatment nave, and 10% received prior adjuvant or neoadjuvant platinum-based chemotherapy. KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma in adults (see section 5.1). The median time to onset of colitis was 4.3 months (range 2 days to 24.3 months). 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). Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. BRAF mutations were reported in 302 (36%) patients. 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. Response: Best objective response as confirmed complete response or partial response. Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo. Tourist area. The option to use bevacizumab was by investigator choice prior to randomisation. When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. In patients with HNSCC treated with pembrolizumab as monotherapy (n=909), the incidence of hypothyroidism was 16.1% (all Grades) with 0.3% Grade 3. << Paclitaxel 175 mg/m2 + carboplatin AUC 5 mg/mL/min + bevacizumab 15 mg/kg. COVID-19 cases were confirmed by polymerase chain reaction (PCR) through a central laboratory. For patients who completed 24 months of therapy or had a complete response, treatment with pembrolizumab could be reinitiated for disease progression and administered for up to 1 additional year. 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. Sixty-one percent of patients had received ASCT, 38% were transplant ineligible; 17% had no prior brentuximab vedotin use; and 37% of patients had prior radiation therapy. New information on this medicinal product will be reviewed at least every year and this SmPC will be updated as necessary. Table 43: Efficacy results in KEYNOTE-826 for patients with PD-L1 expression (CPS 1), Pembrolizumab 200 mg every 3 weeks plus Chemotherapy* with or without bevacizumab, Placebo plus Chemotherapy* with or without bevacizumab, * Chemotherapy (paclitaxel and cisplatin or paclitaxel and carboplatin), The median duration was 1.1 month (range 1 day to 45.2 months). A decision should be made whether to discontinue breast-feeding or to discontinue pembrolizumab, taking into account the benefit of breast-feeding for the child and the benefit of pembrolizumab therapy for the woman. /Type /Metadata The primary efficacy analysis population (referred to as the Per-Protocol Efficacy [PP-EFF] analysis set) included 25,452 participants who received either Nuvaxovid (n = 17,312) or placebo (n = 8,140), received two doses (Dose 1 on day 0; Dose 2 at day 21, median 21 days [IQR 21-23], range 14-60), did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infection through 7 days after the second dose. Well send you a link to a feedback form. The safety profile in paediatric patients was generally similar to that seen in adults treated with pembrolizumab. It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. There were no notable effects in the male and female reproductive organs in monkeys based on 1-month and 6-month repeat-dose toxicity studies (see section 5.3). 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. Expires . KEYNOTE-024: Controlled study of NSCLC patients nave to treatment. /MediaBox [0 0 595 842] Results for PFS with and without censoring for new anti-cancer treatment were consistent. This medicinal product has been authorised under a so-called conditional approval scheme. Efficacy results for OS were consistent regardless of the age of tumour specimen (new vs. archival) based on an intergroup comparison. No specific factor(s) associated with early deaths could be identified. Treatment could continue beyond disease progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. 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. Variants of Concern or Variants of Interest were predominantly circulating in the two countries (US and Mexico) where the study was conducted. There are no notable differences in median Cmax between cHL and other tumour types. 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. Qualitative and quantitative composition 3. Randomisation was stratified by chemotherapy treatment (paclitaxel or nab-paclitaxel vs. gemcitabine and carboplatin), tumour PD-L1 expression (CPS 1 vs. CPS < 1), and prior treatment with the same class of chemotherapy in the neoadjuvant setting (yes vs. no). Store the opened vial between 2C to 25C for up to 6 hours after first puncture, see section 6.3. Name of the medicinal product 2. Bohumil 138 A total of 976 patients were randomised (1:1) to receive pembrolizumab 200 mg every three weeks (or the paediatric [12 to 17 years old] dose of 2 mg/kg intravenously [up to a maximum of 200 mg] every three weeks) (n=487) or placebo (n=489), for up to one year or until disease recurrence or unacceptable toxicity. 14 0 obj *produced by recombinant DNA technology using a baculovirus expression system in an insect cell line that is derived from Sf9 cells of the Spodoptera frugiperda species. Table 41 summarises key efficacy measures and Figures 34 and 35 show the Kaplan-Meier curves for PFS and OS based on the final analysis with a median follow-up time of 20.2 months (range: 0.3 to 53.1 months) for patients with tumour PD-L1 expression CPS 10. Patients without disease progression could be treated for up to 24 months. SPC Flooring. endobj Treatment could continue beyond progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. /Type /Page 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). The baseline characteristics of these 383 patients were: median age of 63 years (range: 28 to 89), 41% age 65 or older; 82% male; 34% White and 56% Asian; 43% and 57% had an ECOG performance status of 0 and 1, respectively. These results reflect enrolment that occurred during the time period when the B.1.17 (Alpha) variant was circulating in the UK. PFS and ORR results are reported from an interim analysis at a median follow-up of 11 months. In the event of an overdose, monitoring of vital functions and possible symptomatic treatment is recommended. 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). The study demonstrated a statistically significant improvement in OS (HR 0.53; 95% CI 0.38, 0.74; p-Value=0.00005) and PFS (HR 0.69; 95% CI 0.56, 0.84; p-Value=0.00012) for patients randomised to the pembrolizumab combination arm compared with sunitinib at its pre-specified interim analysis. 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).. This is based on the MHRA assessment report with any commercially or personally confidential information removed. 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). 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. Withdraw the required volume up to 4 mL (100 mg) of concentrate and transfer into an intravenous bag containing sodium chloride 9 mg/mL (0.9%) or glucose 50 mg/mL (5%) to prepare a diluted solution with a final concentration ranging from 1 to 10 mg/mL. H0: difference in % = 0 versus H1: difference in % > 0, Nominal p-Value based on Miettinen and Nurminen method stratified by IMDC risk group and geographic region. MSI or MMR tumour status was determined prospectively using PCR or IHC, respectively. Great Britain. In patients with cHL (n=389) the incidence of hypothyroidism was 17%, all of which were Grade 1 or 2. 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. MHRA July 2018 Pressurised metered dose inhalers (pMDI): risk of airway obstruction from aspiration of loose objects. 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. Table 20: Efficacy results in KEYNOTE-087 and KEYNOTE-013, The following factors had no clinically important effect on the clearance of pembrolizumab: age (range 15-94 years), gender, race, mild or moderate renal impairment, mild or moderate hepatic impairment and tumour burden. /MediaBox [0 0 595 842] 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. Report a side effect with a medicine or medical device. This SCA should be read in conjunction with the Summary of Product Characteristics (SPC) and the current edition of the British National Formulary . An updated OS analysis was performed when patients receiving pembrolizumab and lenvatinib or sunitinib had a median survival follow-up of 33.4 months. The primary efficacy outcome measure was ORR as assessed by BICR using RECIST 1.1. Based on stratified log-rank test (compared to an alpha boundary of 0.00549), Based on the stratified Cox regression model, endobj >> Dont worry we wont send you spam or share your email address with anyone. A secondary efficacy outcome measure was OS. The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). Among patients with BRAF mutant tumours, 10 (50%) were previously treated with a BRAF inhibitor. Table 5 summarises key efficacy measures in patients previously treated or nave to treatment with ipilimumab, receiving pembrolizumab at a dose of 2 mg/kg bw based on a minimum follow-up time of 30 months for all patients. 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). Of the 161 patients, 137 were enrolled with solid tumours, 22 with Hodgkin lymphoma, and 2 with other lymphomas. All patients received pembrolizumab for a median of 4 doses (range 1-35 doses), with 138 patients (85.7%) receiving pembrolizumab for 2 doses or more. For the neoadjuvant and adjuvant treatment of TNBC, patients should be treated with neoadjuvant KEYTRUDA in combination with chemotherapy for 8 doses of 200 mg every 3 weeks or 4 doses of 400 mg every 6 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as monotherapy for 9 doses of 200 mg every 3 weeks or 5 doses of 400 mg every 6 weeks or until disease recurrence or unacceptable toxicity. The study excluded patients with autoimmune disease or a medical condition that required immunosuppression. Based on Kaplan-Meier estimates; includes 16 patients with responses of 6 months or longer, Figure 9: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-024 (intent to treat population). For Grades 3 or 4 myocarditis, encephalitis or Guillain-Barr syndrome, pembrolizumab should be permanently discontinued (see sections 4.2 and 4.8). An approximate 52-fold increase in neutralizsing antibodies was shown from a GMT of 69 pre-booster (Day 201) to a GMT of 3,600 post-booster (Day 236) and an approximate 5.2-fold increase from a peak GMT (14 days post-Dose 2) of 694. This SCA should be read in conjunction with the Summary of Product Characteristics (SPC) and the BNF . Sixteen percent had stage IIIA; 46% had stage IIIB; 18% had stage IIIC (1-3 positive lymph nodes) and 20% had stage IIIC ( 4 positive lymph nodes); 50% were BRAF V600 mutation positive and 44% were BRAF wild-type. Limited data are currently available on response duration following pembrolizumab discontinuation at cycle 35. Key eligibility criteria were locally recurrent unresectable or metastatic TNBC, regardless of tumour PD-L1 expression, not previously treated with chemotherapy in the advanced setting. 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