Administration of pembrolizumab and axitinib was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults and adolescents aged 12 years and older with Stage IIB, IIC or III melanoma and who have undergone complete resection (see section 5.1). The frequencies are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. These noninferiority criteria were met. In the Hodgkin lymphoma population (n=22), in patients aged 11 years to 17 years, the baseline characteristics were median age 15 years; 64% male; 68% White; 77% had a Lansky/Karnofsky scale 90-100 and 23% had scale 70-80. At the time of vaccination, the median age was 48 years (range 18 to 95 years). The PFS HR (95% CI) for the favourable, intermediate and poor risk groups were 0.81 (0.53, 1.24), 0.69 (0.53, 0.90) and 0.58 (0.35, 0.94), respectively. However, due to the exploratory nature of this subgroup analysis, no definitive conclusions can be drawn. A subset of 104 participants received a booster dose of Nuvaxovid approximately 6months after receiving Dose2 of the primary series. Qualitative and quantitative composition 3. 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. Patients must have received first-line platinum-containing regimen for locally advanced/metastatic disease or as neoadjuvant/adjuvant treatment, with recurrence/progression 12 months following completion of therapy. Nephritis resolved in 20 patients, 5 with sequelae. Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. All patients had a tumour histology of adenocarcinoma. Please refer to the UK approved SPC and PIL supplied electronically with the German 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. KEYTRUDA as monotherapy is indicated for the adjuvant treatment of adults with renal cell carcinoma at increased risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions (for selection criteria, please see section 5.1). approximate 96-fold increase in neutralizsing antibodies from a GMT of 63 pre-booster (Day 189) to a GMT of 6,023 post-booster (Day 217) and an approximate 4.1-fold increase from a peak GMT (14 days post-Dose 2) of 1,470. This product is considered high in sodium. /Resources 22 0 R 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. In this patient population, the most frequent adverse reactions were anaemia (55%), nausea (54%), fatigue (38%), neutropenia (36%), constipation (35%), alopecia (35%), diarrhoea (34%), vomiting (28%), and decreased appetite (27%). Hypothyroidism resolved in 200 (21.3%) patients, 16 with sequelae. Corticosteroid therapy may be considered. Table 36: Efficacy results in KEYNOTE-177. Tumour response was assessed at 12-week intervals. The clinical efficacy, safety, and immunogenicity of Nuvaxovid is being evaluated in two pivotal, placebo-controlled, Phase 3 studies, Study 1 (2019nCoV-301) conducted in North America and Study 2 (2019nCoV-302) conducted in the United Kingdom, and a Phase 2a/b study, Study 3, conducted in South Africa. Healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis. Patients with Grades 1 or 2 infusion reaction may continue to receive pembrolizumab with close monitoring; premedication with antipyretic and antihistamine may be considered. Want to buy mhra spc,we are best mhra spc suppliers,manufacturers,wholesalers from China. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. Two-sided based on stratified log-rank test, Forty-five percent had no prior therapies for advanced melanoma. Do not co-administer other medicinal products through the same infusion line. The median duration was not reached (range 3 days to 40.1+ months). A total of 861 patients were randomised. 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). It is not intended to provide practical advice on how to use this product. 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 baseline characteristics of the 323 patients with tumour PD-L1 expression CPS 10 included: median age of 53 years (range: 22 to 83); 20% age 65 or older; 100% female; 69% White, 20% Asian, and 5% Black; ECOG performance status of 0 (61%) and 1 (39%); 67% were post-menopausal status; 3% had a history of brain metastases; and 20% had disease-free interval of < 12 months. The efficacy of pembrolizumab was investigated in KEYNOTE-087 and KEYNOTE-013, two multicentre, open-label studies for the treatment of 241 patients with cHL. These results reflect enrolment that occurred during the time period when the B.1.17 (Alpha) variant was circulating in the UK. Novavax CZ a.s. If you are concerned about an adverse event, it should be reported on a Yellow card. Go to Products website to find information on medicines. specialist and MHRA yellow card scheme. 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. Date of revision of the text From a microbiological point of view, the product, once diluted, should be used immediately. Use of pembrolizumab in urothelial carcinoma for patients who are considered ineligible for cisplatin-containing chemotherapy and whose tumours express PD-L1 with CPS 10. COVID-19 cases were confirmed by polymerase chain reaction (PCR) through a central laboratory. Patients with active autoimmune disease, a medical condition that required immunosuppression, or known HER-2 positive GEJ adenocarcinoma patients were ineligible for the study. 3 0 obj 2, Higher frequencies of these events were observed after the second dose. This is based on the MHRA assessment report with any commercially or personally confidential information removed. A total of 559 patients were randomised. Assessment of tumour status was performed every 9 weeks for the first 45 weeks, and every 12 weeks thereafter. Wed like to set additional cookies to understand how you use GOV.UK, remember your settings and improve government services. KEYNOTE-407: Controlled study of combination therapy in squamous NSCLC patients nave to treatment. Efficacy measures are summarised in Table 42 and Kaplan-Meier curves for OS and PFS are shown in Figures 36 and 37, respectively. >> R. eview. QRjj$HUwg 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. endobj Based on a pre-specified EFS interim analysis (compared to a significance level of 0.0052), The primary efficacy outcome measure was investigator-assessed disease-free survival (DFS). /Parent 3 0 R Pembrolizumab should not be used during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. Marketing authorisation holder 8. Patients with non-squamous NSCLC could receive pemetrexed maintenance.). This updated OS analysis was not adjusted to account for subsequent therapies. The median duration of the post-progression therapy was 2.8 months. /Rotate 0 Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. Mix diluted solution by gentle inversion. 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. KEYTRUDA is for intravenous use. PDFBox << 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, Table 39: Efficacy results for pembrolizumab plus chemotherapy in KEYNOTE-590 with PD-L1 expression (CPS 10), /ProcSet [/PDF /Text] Elevated liver enzymes when pembrolizumab is combined with axitinib in RCC. myositis (myalgia, myopathy, necrotising myositis, polymyalgia rheumatica and rhabdomyolysis), dd. 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. /Type /Page The primary efficacy outcome measures were OS and PFS as assessed by BICR using RECIST 1.1. There was no statistically significant difference between pembrolizumab and chemotherapy with respect to PFS. The baseline characteristics of these 599 patients included: median age 63 years (45% age 65 or older); 69% male; 63% White and 32% Asian; 17% Hispanic or Latino; and ECOG performance status 0 and 1 in 31% and 69%, respectively. Assessment of tumour status was performed at 9 weeks, then every 6 weeks through Week 52, followed by every 9 weeks through 24 months. The study excluded patients with endometrial sarcoma, carcinosarcoma, pre-existing Grade 3 fistula, uncontrolled BP (> 150/90 mmHg), significant cardiovascular impairment or event within previous 12 months, or patients who had active autoimmune disease or a medical condition that required immunosuppression. Every medicine pack includes a patient information leaflet (PIL), which provides information on using the medicine safely. Use of pembrolizumab in combination with axitinib for first-line treatment of patients with RCC. In clinical studies in patients treated with pembrolizumab 2 mg/kg bw every three weeks, 200 mg every three weeks, or 10 mg/kg bw every two or three weeks as monotherapy, 36 (1.8%) of 2,034 evaluable patients tested positive for treatment-emergent antibodies to pembrolizumab, of which 9 (0.4%) patients had neutralising antibodies against pembrolizumab. >> Thyroid disorders, including hypothyroidism, hyperthyroidism and thyroiditis, have been reported in patients receiving pembrolizumab and can occur at any time during treatment. 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. endobj 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. 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