Eighty-one percent had a primary tumour in the lower tract, and 19% of patients had a primary tumour in the upper tract. The geometric mean value (CV%) for the terminal half-life is 22 days (32%) at steady-state. KEYTRUDA, in combination with chemotherapy with or without bevacizumab, is indicated for the treatment of persistent, recurrent, or metastatic cervical cancer in adults whose tumours express PD-L1 with a CPS 1. Hepatitis has been reported in patients receiving pembrolizumab (see section 4.8). Elevated liver enzymes when pembrolizumab is combined with axitinib in RCC. 4.9 Overdose Hyperkalaemia. HWS6_Hb,GKBLg;Nmva~i?~>Fvq59>LDz1b'~: X.i5jNq].gS1 k$~yr;_6Z\!*'+0W0SY3FuHI43#}l|Q~pg$S)-HPWl8{{n/f:9 9c(|2(?f`o$8H,$4E<>sQQvAck2eShaEx:o`lP7r4kDqk2E9adV&! All prescribers of KEYTRUDA must be familiar with the Physician Information and Management Guidelines. The median duration of treatment for pembrolizumab plus lenvatinib was 17.0 months. % Each vial contains an excess fill of 0.25 mL (total content per vial 4.25 mL) to ensure the recovery of 4 mL of concentrate. In 20 subjects with ocular melanoma included in KEYNOTE-001, no objective responses were reported; stable disease was reported in 6 patients. Table 17: Efficacy results by PD-L1 expression in KEYNOTE-407 Storage at 25C is not the recommended storage or shipping condition but may guide decisions for use in case of temporary temperature excursions during the 9-month storage at 2C to 8C. A certificate of Good Manufacturing Practice (GMP) is issued to a manufacturer if the outcome of the inspection confirms that the manufacturer complies with the principles of Good Manufacturing Practice. KEYNOTE-826: Controlled study of combination therapy in patients with persistent, recurrent, or metastatic cervical cancer. Adverse reactions known to occur with pembrolizumab or combination therapy components given alone may occur during treatment with these medicinal products in combination, even if these reactions were not reported in clinical studies with combination therapy. The most frequent adverse reactions were injection site tenderness (71%), injection site pain (67%), headache (63%), myalgia (57%), fatigue (54%), malaise (43%), nausea or vomiting (23%), arthralgia (19%) and pyrexia (17%). Ninety-six percent of patients had M1 disease and 4% M0 disease. The relationship between body weight and clearance supports the use of either fixed dose or body weight-based dosing to provide adequate and similar control of exposure. /Type /Page In these paediatric patients with cHL, the ORR assessed by BICR according to the IWG 2007 criteria was 54.5%, 1 patient (4.5%) had a complete response and 11 patients (50.0%) had a partial response, and the ORR assessed by the Lugano 2014 criteria was 63.6%, 4 patients (18.2%) had a complete response and 10 patients (45.5%) had a partial response. The frequencies included below and in Table 2 are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. There were no Grade 5 hepatic events. /Rotate 0 Otherwise treatment should be discontinued. Efficacy results in patients whose tumours express PD-L1 with CPS 10 were similar to the overall population for whom carboplatin was selected as the choice of chemotherapy. Non-clinical data reveal no special hazard for humans based on conventional studies of repeat-dose toxicity, local tolerance, genotoxicity, and reproductive and developmental toxicity. Great Britain. When pembrolizumab is administered in combination, refer to the SmPC for the respective combination therapy components prior to initiation of treatment. Data about efficacy of pembrolizumab in combination with platinum chemotherapy are limited in this patient population. Five study subjects were ineligible to ASCT due to reasons other than failure to salvage chemotherapy. Use within 6 hours after first puncture. British National Formulary accessed online sept 2019 3. << rApxg0; pInZvM7t`e}atCV"Jo*)myf4hlpFOQ ?P95oABh-_+k/GXsu|*A" l~x6\x3;4R]> /^kLsj4>4" \uYU CMMBs I }r2br?z7TB7wfhvF\lT1_},qb7Vi The median number of prior lines of therapy administered for the treatment of cHL was 4 (range 1 to 12). No case of overdose has been reported. In the PP-EFF analysis set for participants who received Nuvaxovid, median age was 56.0 years (range: 18 to 84 years); 72% (n = 5,067) were 18 to 64 years old and 28% (n = 1,953) were aged 65 to 84; 49% were female; 94% were White; 3% were Asian; 1% were multiple races, <1% were Black or African American; and <1% were Hispanic or Latino; and 45% had at least one comorbid condition. /ModDate (D:20190624094123+01'00') KEYTRUDA 25 mg/mL concentrate for solution for infusion. 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). Patients randomised to chemotherapy were offered pembrolizumab at the time of disease progression. Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer. The safety of pembrolizumab was evaluated in a 1-month and a 6-month repeat-dose toxicity study in Cynomolgus monkeys administered intravenous doses of 6, 40 or 200 mg/kg bw once a week in the 1-month study and once every two weeks in the 6-month study, followed by a 4-month treatment-free period. Patients with clinically significant renal (creatinine > 1.5 x ULN) or hepatic (bilirubin > 1.5 x ULN, ALT, AST > 2.5 x ULN in the absence of liver metastases) abnormalities at baseline were excluded from clinical studies, therefore information is limited in patients with severe renal and moderate to severe hepatic impairment. Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. Treatment with pembrolizumab and axitinib continued until RECIST v1.1-defined progression of disease as verified by BICR or confirmed by the investigator, unacceptable toxicity, or for pembrolizumab, a maximum of 24 months. Rare cases of SJS and TEN, some of them with fatal outcome, have been observed (see sections 4.2 and 4.4). stream 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. Nephritis led to discontinuation of pembrolizumab in 17 (0.2%) patients. Updated efficacy results with a median follow-up time of 29.7 months are summarised in Table 35 and Figure 27. Physicians should consider the benefit/risk balance of the available treatment options (pembrolizumab monotherapy or pembrolizumab in combination with lenvatinib) before initiating treatment in patients with advanced or recurrent MSI-H or dMMR endometrial carcinoma. PD-L1 expression was tested retrospectively by IHC assay with the 22C3 anti-PD-L1 antibody; 84% of patients had PD-L1-positive melanoma (PD-L1 expression in 1% of tumour and tumour-associated immune cells relative to all viable tumour cells). 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. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT), Allogeneic HSCT after treatment with pembrolizumab. Table 2: Adverse reactions in patients treated with pembrolizumab*, In combination with axitinib or lenvatinib, neutropenia, anaemia, thrombocytopenia, leukopenia, thrombocytopenia, neutropenia, lymphopenia, neutropenia, thrombocytopenia, lymphopenia, leukopenia, leukopenia, immune thrombocytopenia, eosinophilia, haemolytic anaemia, pure red cell aplasia, haemophagocytic lymphohistiocytosis, haemolytic anaemia, immune thrombocytopenia, adrenal insufficiencyc, thyroiditisd, hyperthyroidisme, adrenal insufficiencyc, hyperthyroidism, thyroiditisd, adrenal insufficiencyc, hypophysitisf, thyroiditisd, hyponatraemia, hypokalaemia, hypocalcaemia, neuropathy peripheral, headache, dizziness, dysgeusia, dizziness, neuropathy peripheral, lethargy, dysgeusia, dizziness, neuropathy peripheral, lethargy, Guillain-Barr syndromej, encephalitisi, myelitisk, meningitis (aseptic)l, Guillain-Barr syndromej, myasthenic syndrome, cardiac arrhythmia (including atrial fibrillation), myocarditis, pericardial effusion, pericarditis, myocarditisn, pericardial effusion, pericarditis, Respiratory, thoracic and mediastinal disorders, diarrhoea, abdominal painq, nausea, vomiting, constipation, nausea, diarrhoea, vomiting, abdominal painq, constipation, colitisr, pancreatitiss, gastritis, dry mouth, pancreatitiss, gastritis, gastrointestinal ulcerationt, pancreatitiss, gastrointestinal ulcerationt, severe skin reactionsy, erythema, dermatitis, dry skin, vitiligoz, eczema, alopecia, dermatitis acneiform, severe skin reactionsy, erythema, dermatitis acneiform, dermatitis, dry skin, eczema, severe skin reactionsy, dermatitis, dry skin, erythema, dermatitis acneiform, alopecia, psoriasis, lichenoid keratosisaa, papule, hair colour changes, psoriasis, lichenoid keratosisaa, vitiligoz, papule, eczema, lichenoid keratosisaa, psoriasis, vitiligoz, papule, hair colour changes, Stevens-Johnson syndrome, erythema nodosum, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema nodosum, hair colour changes, toxic epidermal necrolysis, Stevens-Johnson syndrome, Musculoskeletal and connective tissue disorders, arthralgia, musculoskeletal painbb, myositiscc, arthralgia, musculoskeletal painbb, myositiscc, pain in extremity, myositiscc, pain in extremity, arthritisdd, General disorders and administration site conditions, alanine aminotransferase increased, aspartate aminotransferase increased, lipase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased, blood creatinine increased, blood creatinine increased, blood alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased, amylase increased, blood bilirubin increased, blood alkaline phosphatase increased, hypercalcaemia. Within the group assigned to receive Nuvaxovid, 115 participants received a two-dose primary series of ChAdOx1 nCov-19 and 114 participants received a two-dose primary series of BNT162b2, prior to receiving a single booster dose (0.5 mL) of Nuvaxovid. The recommended dose of KEYTRUDA as monotherapy in paediatric patients aged 3 years and older with cHL or patients aged 12 years and older with melanoma is 2 mg/kg bodyweight (bw) (up to a maximum of 200 mg), every 3 weeks administered as an intravenous infusion over 30 minutes. Safety data were collected in 2,232 participants 12 through 17 years of age, with and without evidence of prior SARS CoV-2 infection, in United States who received at least one dose of Nuvaxovid (n=1,487) or placebo (n=745). Immune-related adverse reactions affecting more than one body system can occur simultaneously. Clear to slightly opalescent, colourless to slightly yellow solution, pH 5.2 5.8. Of the 540 patients, 61% were male, 43% were 65 years (median age was 62 years [range 15-89]) and 98% were white. SHCP APC . One dose (0.5 mL) contains 5 micrograms of the of SARS-CoV-2 spike protein* and is adjuvanted with Matrix-M. Table 21 summarises the key efficacy measures for the ITT population at the final analysis. 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). The safety of pembrolizumab as monotherapy has been evaluated in 7,631 patients across tumour types and across four doses (2 mg/kg bw every 3 weeks, 200 mg every 3 weeks, or 10 mg/kg bw every 2 or 3 weeks) in clinical studies. 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. 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. These noninferiority criteria were met. No specific factor(s) associated with early deaths could be identified. The study demonstrated statistically significant improvements in PFS, OS, and ORR in patients randomised to pembrolizumab in combination with lenvatinib compared with sunitinib. Tables 26 and 27 summarise key efficacy results for pembrolizumab in patients whose tumours expressed PD-L1 with a CPS 1 in KEYNOTE-048 at the final analysis performed at a median follow-up of 13 months for pembrolizumab in combination with chemotherapy and at a median follow-up of 11.5 months for pembrolizumab monotherapy. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-002, a multicentre, double-blind, controlled study for the treatment of advanced melanoma in patients previously treated with ipilimumab and if BRAF V600 mutation-positive, with a BRAF or MEK inhibitor. Table 14 summarises key efficacy measures and Figures 11 and 12 show the Kaplan-Meier curves for OS and PFS based on the final analysis with a median follow-up of 18.8 months. Pembrolizumab in combination with tyrosine kinase inhibitor (TKI) (see section 4.2). Figure 26: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-581. The median follow-up time in months was 21.9 (range: 1.5 to 64.0) for endometrial, 13.9 (range: 1.1 to 66.9) for gastric, 29.1 (4.2 to 67.7) for small intestine, and 19.4 (range: 1.1 to 60.8) for biliary cancer. Starting from randomisation, patients underwent imaging every 12 weeks for the first 2 years, then every 16 weeks from year 3 to 5, and then every 24 weeks annually. This medicinal product is subject to additional monitoring. Persons who experienced severe reactions following the second dose may be more likely to experience severe reactions following the third dose. Upon enrolment, participants were stratified by age (18 to 64 years; 65 to 84 years) to receive Nuvaxovid or placebo. The median interval between the second and the third doses was 165 days. Among the 22 patients with biliary cancer, the baseline characteristics were: median age 61 years (range: 40 to 77); 41% age 65 or older; 73% male, 91% White, 9% Asian; ECOG PS 0 (45%) and 1 (55%); and 82% M1 disease and 18% M0 disease. In the PP-EFF analysis set for participants who received Nuvaxovid, the median age was 47 years (range: 18 to 95 years); 88% (n = 15,264) were 18 to 64 years old and 12% (n = 2,048) were aged 65 and older; 48% were female; 94% were from the United States and 6% were from Mexico; 76% were White, 11% were Black or African American, 6% were American Indian (including Native Americans) or Alaskan Native, and 4% were Asian; 22% were Hispanic or Latino. It is not. Tourist area. 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). The key eligibility criteria for this study were locally advanced, inflammatory, or early-stage TNBC at high risk of recurrence (tumour size > 1 cm but 2 cm in diameter with nodal involvement or tumour size > 2 cm in diameter regardless of nodal involvement), regardless of tumour PD-L1 expression. The recent introduction of a licensed product, advice for the MHRA regarding imported products and Area Prescribing Committee support has facilitated the participation of GPs in shared care. In addition, no safety and efficacy data are available in frailer patients (e.g. Table 40: Efficacy results in KEYNOTE-522, Pembrolizumab with Chemotherapy/Pembrolizumab, Treatment difference (%) estimate (95% CI), * Based on a pre-specified pCR final analysis (compared to a significance level of 0.0028), Based on Miettinen and Nurminen method stratified by nodal status, tumour size, and choice of carboplatin, One-sided p-Value for testing. 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). The secondary outcome measures were distant metastasis-free survival (DMFS) and OS in the whole population. Extension (Km 2 ) 141. Nephritis resolved in 20 patients, 5 with sequelae. /Rotate 0 This information is for use by healthcare professionals. Liver enzymes should be monitored before initiation of and periodically throughout treatment. Response was assessed every 12 weeks, with the first planned post-baseline assessment at Week 12. Pembrolizumab has a minor influence on the ability to drive and use machines. *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. The primary OS analysis was not adjusted to account for subsequent therapies. %PDF-1.4 Study 2 is an ongoing Phase 3, multicentre, randomised, observer-blinded, placebo-controlled study in participants 18 to 84 years of age in the United Kingdom. Use of pembrolizumab for first-line treatment of patients with NSCLC. In all patients randomised to pembrolizumab in combination with chemotherapy, compared to chemotherapy the OS HR was 0.73 (95% CI 0.62-0.86) and the PFS HR was 0.65 (95% CI 0.55-0.76). /Length 33 0 R /Filter /FlateDecode This will allow quick identification of new safety information. The most frequent solicited adverse reactions were injection site tenderness (81%), fatigue (63%), injection site pain (55%), muscle pain (51%), malaise (47%) and headache (46%), joint pain (29%), and fever (17%) with a median duration of 1 to 3days following vaccination. 5 mL of dispersion in a vial (type I glass) with a stopper (bromobutyl rubber) and an aluminium overseal with blue plastic flip-off cap. The median duration was not reached (range 3 days to 40.1+ months). Enrolment of adolescents completed in June 2021. Based on Miettinen and Nurminen method stratified by MMR Status, ECOG performance status, geographic region, and history of pelvic radiation, Figure 36: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-775 (intent to treat population), Figure 37: Kaplan-Meier curve for progression free-survival by treatment arm in KEYNOTE-775 (intent to treat population). Secondary efficacy outcome measures were ORR and response duration. These results should be interpreted in the context of the open-label study design and therefore taken cautiously. No patients experienced engraftment syndrome post-transplant. Physicians should consider the delayed onset of pembrolizumab effect before initiating treatment in patients with poorer prognostic features and/or aggressive disease. Treatment could continue beyond progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. 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. Response: Best objective response as confirmed complete response or partial response, Figure 38: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-826 patients with PD-L1 expression (CPS 1), * Chemotherapy (paclitaxel and cisplatin or paclitaxel and carboplatin) with or without bevacizumab, Figure 39: Kaplan-Meier curve for progression free survival by treatment arm in KEYNOTE-826 patients with PD-L1 expression (CPS 1). Adverse reactions were usually mild to moderate in severity with a median duration of less than or equal to 2 days for local events and less than or equal to 1 day for systemic events following vaccination. Secondary efficacy outcome measures included response duration, PFS, and OS. Approval date: September 2019, updated December 2019 Review date: December 2021 (or earlier if indicated) South East London Area Prescribing Committee. /Type /Metadata The median duration was 1.6 months (range 4 days to 43.1+ months). /Parent 3 0 R An updated OS analysis was performed when patients receiving pembrolizumab and lenvatinib or sunitinib had a median survival follow-up of 33.4 months. Key eligibility criteria were metastatic non-squamous NSCLC, no prior systemic treatment for metastatic NSCLC, and no EGFR or ALK genomic tumour aberrations. >> If you are unable to complete your LogIn successfully please contact the Adverse Incident Centre for assistance and advice: sabre@mhra.gov.uk or 020 3080 7336.