When used in combination with lenvatinib, one or both medicines should be interrupted as appropriate. Among the 124 patients enrolled in KEYNOTE-164, the baseline characteristics were: median age 56 years (35% age 65 or older); 56% male; 68% White, 27% Asian; 41% and 59% had an ECOG performance status of 0 and 1, respectively. In patients with cHL (n=389) the incidence of hypothyroidism was 17%, all of which were Grade 1 or 2. * With additional 12 months of follow-up after the pre-specified final analysis for PFS. In KEYNOTE-361, a higher number of deaths within 6 months of treatment initiation followed by a long-term survival benefit was observed with pembrolizumab monotherapy compared to chemotherapy (see section 5.1). 12 0 obj The primary OS analysis was not adjusted to account for subsequent therapies. HWS6_Hb,GKBLg;Nmva~i?~>Fvq59>LDz1b'~:
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9c(|2(?f`o$8H,$4E<>sQQvAck2eShaEx:o`lP7r4kDqk2E9adV&! 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). There are no notable differences in median Cmax between cHL and other tumour types. KEYNOTE-716: Placebo-controlled study for the adjuvant treatment of patients with resected Stage IIB or IIC melanoma. Patients were treated with pembrolizumab until unacceptable toxicity or disease progression. The median trough concentrations (Cmin) at steady-state were approximately 22 mcg/mL at a dose of 2 mg/kg bw every 3 weeks and 29 mcg/mL at a dose of 200 mg every 3 weeks. Immune-related adverse reactions affecting more than one body system can occur simultaneously. The median survival follow-up time was 26.5 months. KEYTRUDA as monotherapy is indicated for adults with MSI-H or dMMR colorectal cancer in the following settings: - first-line treatment of metastatic colorectal cancer; - treatment of unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy. Patients in the placebo arm were offered pembrolizumab as a single agent at the time of disease progression. . Tumour response was assessed at 12-week intervals. Limited data are currently available on response duration following pembrolizumab discontinuation at cycle 35. The study population characteristics were: median age of 62 years (range: 26 to 90); 38% age 65 or older; 73% male; 79% White and 16% Asian; 80% had a Karnofsky Performance Score (KPS) 90-100 and 20% had KPS 70-80; patient distribution by IMDC risk categories was 31% favourable, 56% intermediate and 13% poor. No dose adjustment is needed for patients with mild or moderate renal impairment. You can also use the A-Z list to find the active substance. Uncommon but serious: (see MHRA alerts below for more information) DKA Fournier's Gangrene Lower limb amputation -encourage regular preventative footcare Please see individual drug monographs in BNF/SPC for a complete side-effect profile -see hyperlink in table overleaf. Start typing to retrieve search suggestions. - Minor change to SmPC text on myo/pericarditis. Among the 5 adolescent participants with advanced melanoma treated on KEYNOTE-051, no patient had a complete or a partial response, and 1 patient had stable disease. Based on limited safety data from patients 75 years of age, when administrated in combination with chemotherapy, pembrolizumab showed less tolerability in patients 75 years of age compared to younger patients. Randomisation was stratified by tumour PD-L1 expression (TPS < 1% [negative] vs. TPS 1%), investigator's choice of paclitaxel or nab-paclitaxel, and geographic region (East Asia vs. non-East Asia). Following administration of pembrolizumab 200 mg every 3 weeks in patients with cHL, the observed median Cmin at steady-state was up to 40% higher than that in other tumour types treated with the same dosage; however, the range of trough concentrations is similar. No. Thyroid function and hormone levels should be monitored to ensure appropriate hormone replacement. The primary efficacy outcome measure was investigator-assessed recurrence-free survival (RFS) in the whole population, 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. 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).
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. Table 12 summarises key efficacy measures for the entire intent to treat (ITT) population. As the MHRA website does not include a summary of changes or any sort of version number for the SPC, we are using the "Date . /Rotate 0 endobj Nuvaxovid may also be given as a booster dose in individuals 18 years of age and older following a primary series comprised of an mRNA vaccine or adenoviral vector vaccine (heterologous booster dose). Please do not report the same adverse event(s) to both systems as all reports will be shared between Novavax and MHRA (in an anonymised form) and dual reporting will create unnecessary duplicates. Patients had PD-L1 expression with a 1% TPS based on the PD-L1 IHC 22C3 pharmDxTM Kit. 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. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Thirty-one percent had an ECOG Performance Status of 1, 69% had ECOG Performance Status of 0 and 32% had elevated LDH. Dont include personal or financial information like your National Insurance number or credit card details. Preparation and administration of the infusion. Table 9: Efficacy results by PD-L1 expression in KEYNOTE-006. Table 29: Efficacy results for pembrolizumab plus chemotherapy and pembrolizumab as monotherapy by PD-L1 expression in KEYNOTE-048 (CPS 1 to < 20), Based on the stratified Cox proportional hazard model, Response: Best objective response as confirmed complete response or partial response, KEYNOTE-040: Controlled study in HNSCC patients previously treated with platinum-containing chemotherapy. Data about efficacy of pembrolizumab in combination with chemotherapy are too limited in this patient population. K|m[!X()^5HLWhT7? Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT), Allogeneic HSCT after treatment with pembrolizumab. KEYNOTE-052 also included patients eligible for mono-chemotherapy, for whom no randomised data are available. Pneumonitis resolved in 190 patients, 6 with sequelae. 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. 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. included in other section of SPC. The primary efficacy outcome measure was PFS as assessed by blinded independent central review (BICR) using RECIST 1.1. The primary efficacy outcome measures were OS and PFS as assessed by BICR using RECIST 1.1. 9 0 obj Continue typing to refine. Both studies included patients regardless of PD-L1 expression. BRAF mutations were reported in 13% of the study population. 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. If not used immediately, in-use storage times and conditions are the responsibility of the user. Upon improvement to Grade 1, corticosteroid taper should be initiated and continued over at least 1 month. The safety profile in paediatric patients was generally similar to that seen in adults treated with pembrolizumab. Immune-related adverse reactions (see section 4.4). Key eligibility criteria were metastatic non-squamous NSCLC, no prior systemic treatment for metastatic NSCLC, and no EGFR or ALK genomic tumour aberrations. 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. In this patient population, the median observation time was 8.5 months (range: 1 day to 39 months) and the most frequent adverse reactions with pembrolizumab were fatigue (31%), diarrhoea (22%), and nausea (20%). Cardiology SPC abbreviation meaning defined here. For suspected SJS or TEN, pembrolizumab should be withheld and the patient should be referred to a specialised unit for assessment and treatment. Animal reproduction studies have not been conducted with pembrolizumab; however, in murine models of pregnancy blockade of PD-L1 signalling has been shown to disrupt tolerance to the foetus and to result in an increased foetal loss (see section 5.3). Events of anaphylaxis have been reported with Nuvaxovid vaccines. /Resources 20 0 R Efficacy results by MMR subgroups were consistent with overall study results. The primary efficacy outcome measure was ORR as assessed by BICR using RECIST 1.1. 11 0 obj The Kaplan-Meier curve based on the final analysis for OS is shown in Figure 17. 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 21: Kaplan-Meier curve for overall survival for pembrolizumab as monotherapy in KEYNOTE-048 with PD-L1 expression (CPS 1). Assessment of tumour status was performed every 9 weeks. The safety and efficacy of Nuvaxovid in children aged less than 12 years have not yet been established. The ORR was 66% for pembrolizumab compared to 54% for standard treatment with a p-Value of 0.0225. Assessed by investigator using RECIST 1.1, # One-sided p-Value for testing. 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. Hyperthyroidism resolved in 315 (79.9%) patients, 11 with sequelae. 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