A searchable list of the. Table 17: Efficacy results by PD-L1 expression in KEYNOTE-407 Of the 617 enrolled patients, 548 patients (89%) had tumours expressing PD-L1with a CPS 1 based on the PD-L1 IHC 22C3 pharmDxTM Kit. 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. 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. 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. Hypothyroidism is more frequently reported in patients with HNSCC with prior radiation therapy. Forty-five percent had an ECOG Performance Status of 1, 40% had elevated LDH and 23% had a BRAF mutated tumour. stream Store the opened vial between 2C to 25C for up to 6 hours after first puncture, see section 6.3. The median survival follow-up time was 26.5 months. Table 31: Efficacy results in KEYNOTE-426, Number (%#) of patients with duration 30 months, Based on patients with a best objective response as confirmed complete or partial response. Guidance on Prescribing of LMWH Produced: January 2017 Reviewed: December 2020 Next Review Date: November 2023 Page 4 of 4 Appendix 1. 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. R. eview. /Rotate 0 endobj You have accepted additional cookies. Patients with active autoimmune disease, a medical condition that required immunosuppression, or known HER-2 positive GEJ adenocarcinoma patients were ineligible for the study. The key secondary outcome measure was OS. Sevilla y Entorno. Approval date: September 2019, updated December 2019 Review date: December 2021 (or earlier if indicated) South East London Area Prescribing Committee. Per the pre-specified hierarchical testing order no formal tests for statistical significance of pembrolizumab versus chemotherapy could be performed. Among patients with BRAF mutant tumours, 139 (46%) were previously treated with a BRAF inhibitor. << Patients should be monitored for changes in liver function (at the start of treatment, periodically during treatment and as indicated based on clinical evaluation) and symptoms of hepatitis, and other causes excluded. Assessment of tumour status was performed every 9 weeks through the first year, then every 12 weeks thereafter. The baseline characteristics of these 754 patients included: median age of 61 years (range: 20 to 94); 36% age 65 or older; 82% male; 74% White and 19% Asian; 61% ECOG performance status of 1; and 77% former/current smokers. specialist and MHRA yellow card scheme. Pharmaceutical form 4. It must be administered by infusion over 30 minutes. /Rotate 0 included in other section of SPC. Kaplan-Meier curves for OS and PFS based on the final analysis are shown in Figures 1 and 2. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions (see section 4.4). 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. Prior to dilution, the vial of liquid can be out of refrigeration (temperatures at or below 25C) for up to 24 hours. 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. Jevany, 28163 The study demonstrated statistically significant improvements in PFS, OS, and ORR in patients randomised to pembrolizumab in combination with lenvatinib compared with sunitinib. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-052, a multicentre, open-label study for the treatment of locally advanced or metastatic urothelial carcinoma in patients who were not eligible for cisplatin-containing chemotherapy. Use of pembrolizumab for treatment of patients with advanced or recurrent MSI-H or dMMR endometrial carcinoma. Patients underwent imaging every six months from randomisation through the 4th year, and then once in year 5 from randomisation or until recurrence, whichever came first. The primary efficacy outcome measures were OS and PFS as assessed by the investigator according to RECIST 1.1 in squamous cell histology, CPS 10, and in all patients. For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. An updated OS analysis was performed when patients receiving pembrolizumab and lenvatinib or sunitinib had a median survival follow-up of 33.4 months. Patients who experience disease progression that precludes definitive surgery or unacceptable toxicity related to KEYTRUDA as neoadjuvant treatment in combination with chemotherapy should not receive KEYTRUDA monotherapy as adjuvant treatment. The primary efficacy outcome was OS in the ITT population. Administration of Nuvaxovid in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus. There are no data available on the interchangeability of Nuvaxovid with other COVID-19 vaccines to complete the primary vaccination course. Most immune-related adverse reactions occurring during treatment with pembrolizumab were reversible and managed with interruptions of pembrolizumab, administration of corticosteroids and/or supportive care. Keep the vials in the outer carton in order to protect from light. All but two patients were white. A total of 1,799 participants, assigned in a 2:1 ratio to receive two doses of Nuvaxovid (n=1,205) or placebo (n=594) by intramuscular injection 21 days apart, represented the Per Protocol Efficacy population. Nephritis occurred in 37 (0.5%) patients, including Grade 2, 3 or 4 cases in 11 (0.1%), 19 (0.2%) and 2 (< 0.1%) patients, respectively, receiving pembrolizumab as monotherapy. Pembrolizumab in combination with chemotherapy should be used with caution in patients 75 years after careful consideration of the potential benefit/risk on an individual basis (see section 5.1). Concomitant administration of Nuvaxovid with other vaccines has not been studied. /Resources 18 0 R There was no evidence of an altered pharmacokinetic or safety profile with anti-pembrolizumab binding or neutralising antibody development. /Nums [0 14 0 R] OS was not formally assessed at the time of this analysis. Data about efficacy of pembrolizumab in combination with platinum chemotherapy are limited in this patient population. 2 0 obj 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. This medicinal product must not be mixed with other medicinal products or diluted. 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). Table 16: Efficacy results in KEYNOTE-407, * A total of 138 patients (51%) who discontinued study treatment in the placebo plus chemotherapy arm crossed over to receive monotherapy pembrolizumab or received a checkpoint inhibitor as subsequent therapy, Based on method by Miettinen and Nurminen, 13 0 obj Assessed by investigator using RECIST 1.1, # One-sided p-Value for testing. 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. 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). Table 8 summarises efficacy results by PD-L1 expression. Paclitaxel 175 mg/m2 + carboplatin AUC 5 mg/mL/min + bevacizumab 15 mg/kg. Any questions on the content of this database should be addressed to IE&S-IMT@mhra.gov.uk. Record the date and time of discard on the vial label. The presence of a minor infection and/or low-grade fever should not delay vaccination. If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to use. Treatment with pembrolizumab continued until RECIST v1.1-defined progression of disease, unacceptable toxicity, or a maximum of 24 months. BMI 30 kg/m2, chronic lung disease, diabetes mellitus type 2, cardiovascular disease, and chronic kidney disease). 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). Neutralising antibody titers measured by a wild-type assay were assessed 28 days post-booster dose. /Parent 3 0 R Assessment of tumour status was performed every 8 weeks. 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. The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; current diagnosis or treatment for cancer; autoimmune disease/condition; received chronic immunosuppressive therapy or received immunoglobulin or blood-derived products within 90 days; bleeding disorder or continuous use of anticoagulants; history of allergic reactions and/or anaphylaxis; were pregnant; or had a history of laboratory-confirmed diagnosed COVID-19. In patients with solid tumours and other lymphomas, the ORR was 5.8%, no patient had a complete response and 8 patients (5.8%) had a partial response. Pneumonitis occurred more frequently in patients with a history of prior thoracic radiation (8.1%) than in patients who did not receive prior thoracic radiation (3.9%). This file may not be suitable for users of assistive technology. 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. Factors associated with early deaths were fast progressive disease on prior platinum therapy and liver metastases. Participants with known stable infection with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV) were not excluded from enrolment. At the time of the analysis, a total of 49,950 participants age 18 years and older received at least one dose of the two-dose primary series of Nuvaxovid (n=30,058) or placebo (n=19,892). Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT), Allogeneic HSCT after treatment with pembrolizumab. Of the 540 patients, 61% were male, 43% were 65 years (median age was 62 years [range 15-89]) and 98% were white. 0086 136 9073 4191. domogres@spcfloorings.net. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. The Public Assessment Report will be published shortly. Grades 3-5 adverse reactions in patients with RCC were 80% for pembrolizumab in combination with either axitinib or lenvatinib and 71% for sunitinib alone. Paclitaxel 175 mg/m2 + carboplatin AUC 5 mg/mL/min, 4. 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. Main efficacy results are summarised in Table 20. 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. The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). It explains how this product was assessed and its authorisation recommended, as well as its conditions of use. Consistent with a limited extravascular distribution, the volume of distribution of pembrolizumab at steady-state is small (~6.0 L; CV: 20%). /Contents 15 0 R Tickets cost 17 - 25 and the journey . This publication is licensed under the terms of the Open Government Licence v3.0 except where otherwise stated. Patients with the following conditions were excluded from clinical studies: active CNS metastases; ECOG PS 2 (except for urothelial carcinoma and RCC); HIV infection, hepatitis B or hepatitis C infection; active systemic autoimmune disease; interstitial lung disease; prior pneumonitis requiring systemic corticosteroid therapy; a history of severe hypersensitivity to another monoclonal antibody; receiving immunosuppressive therapy and a history of severe immune-related adverse reactions from treatment with ipilimumab, defined as any Grade 4 toxicity or Grade 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks. Animal reproduction studies have not been conducted with pembrolizumab. Disease characteristics were squamous (37%) and non-squamous (63%); stage IIIA (0.8%); stage IIIB (9%); stage IV (90%); and treated brain metastases (6%). It explains how to use and prescribe a medicine. * The primary analysis of PFS included censoring for new anti-cancer treatment. Pembrolizumab in monotherapy (see section 4.2). endobj KEYNOTE-045: Controlled study in urothelial carcinoma patients who have received prior platinum-containing chemotherapy. The prescriber must discuss the risks of KEYTRUDA therapy with the patient. This information is for use by healthcare professionals. Chemotherapy could continue per standard of care. The clinical significance of this is unknown. search for MHRA Yellow Card in the Google Play or Apple App Store. << The high risk category included: pT4, any Grade N0 and M0; any pT, any Grade with nodal involvement and M0. 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), /Type /Page 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%). 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. In patients with NSCLC, pneumonitis occurred in 8.9% with a history of prior thoracic radiation. 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). Table 41: Efficacy results in KEYNOTE-355 patients with CPS 10, * Chemotherapy: paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin, KEYNOTE-010: Controlled study of NSCLC patients previously treated with chemotherapy. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA. These results reflect enrolment that occurred during the time period when the B.1.351 (Beta) variant was circulating in South Africa. It explains how this product was assessed and its authorisation recommended, as well as its conditions of use. Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. /Rotate 0 From a microbiological point of view, the product, once diluted, should be used immediately. /Filter /FlateDecode , Pyrexia 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. 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. 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