mhra spc

/Contents 23 0 R 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. Liver enzymes should be monitored before initiation of and periodically throughout treatment. The baseline characteristics of these patients were: median age of 63 years (range: 24 to 93), 47% age 65 or older; 50% male; 75% White and 16% Asian; 52% and 48% had an ECOG performance status of 0 or 1, respectively. An analysis was performed in KEYNOTE-407 in patients who had PD-L1 TPS < 1% [pembrolizumab plus chemotherapy arm: n=95 (34%) vs. placebo plus chemotherapy arm: n=99 (35%)], TPS 1% to 49% [pembrolizumab plus chemotherapy arm: n=103 (37%) vs. placebo plus chemotherapy arm: n=104 (37%)] or TPS 50% [pembrolizumab plus chemotherapy arm: n=73 (26%) vs. placebo plus chemotherapy arm: n=73 (26%)] (see Table 17). Patients were randomly assigned to receive pembrolizumab at a dose of 2 mg/kg bw every 3 weeks or 10 mg/kg bw every 3 weeks. A total of 254 participants received two doses of Nuvaxovid (0.5mL 3weeks apart) as the primary vaccination series. /CropBox [0 0 595 842] 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), Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. Assessment of tumour status was performed at baseline and then every 8 weeks. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT), Allogeneic HSCT after treatment with pembrolizumab. R. eview. Participants will be followed for up to 24 months after the second dose for assessments of safety, and efficacy against COVID-19. KEYTRUDA, in combination with lenvatinib, is indicated for the first-line treatment of advanced renal cell carcinoma in adults (see section 5.1). The efficacy of pembrolizumab was evaluated in KEYNOTE-054, a multicentre, randomised, double-blind, placebo-controlled study in patients with completely resected stage IIIA (> 1 mm lymph node metastasis), IIIB or IIIC melanoma. It will take only 2 minutes to fill in. Assessment of tumour status was performed every 9 weeks. Of the 834 patients, 60% were male, 44% were 65 years (median age was 62 years [range 18-89]) and 98% were white. Adrenal insufficiency (primary and secondary) has been reported in patients receiving pembrolizumab. Hi, As an academic sponsor we have are routinely reviewing the MHRA website for any changes to SPCs for our sponsored CTIMPs. 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. You have accepted additional cookies. Patients with active autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible for the study. Tumour response was assessed at 12-week intervals. If specified in the indication, patient selection for treatment with KEYTRUDA based on the tumour expression of PD-L1 should be confirmed by a validated test (see sections 4.1, 4.4, 4.8, and 5.1). When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. Assessment of tumour status was performed every 9 weeks. KEYNOTE-052: Open-label study in urothelial carcinoma patients ineligible for cisplatin-containing chemotherapy. Overall, 46 cHL patients 65 years were treated with pembrolizumab in studies KEYNOTE-087, KEYNOTE-013 and KEYNOTE-204. 7 0 obj 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. /Font 31 0 R KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic non-small cell lung carcinoma in adults whose tumours express PD-L1 with a 50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations. The MHRA products website allows you to find: You can look for any word, phrase or Product Licence number (PL) using the search tool. Ninety percent of patients were treatment nave, and 10% received prior adjuvant or neoadjuvant platinum-based chemotherapy. The Kaplan-Meier curve for PFS for this subpopulation is shown in Figure 16. Randomisation was stratified by geographic region (North America versus Western Europe versus Rest of the World) and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic groups (favourable versus intermediate versus poor). /Contents 19 0 R The study excluded patients with EGFR or ALK genomic tumour aberrations; autoimmune disease that required systemic therapy within 2 years of treatment; a medical condition that required immunosuppression; or who had received more than 30 Gy of thoracic radiation within the prior 26 weeks. Among the 542 randomised patients in KEYNOTE-045, baseline characteristics were: median age 66 years (range: 26 to 88), 58% age 65 or older; 74% male; 72% White and 23% Asian; 56% ECOG performance status of 1 and 1% ECOG performance status of 2; and 96% M1 disease and 4% M0 disease. Assessment of tumour status was performed at Weeks 8, 16, and 24, then every 9 weeks for the first year, and every 12 weeks thereafter. In patients with NSCLC, pneumonitis occurred in 160 (5.7%), including Grade 2, 3, 4 or 5 cases in 62 (2.2%), 47 (1.7%), 14 (0.5%) and 10 (0.4%), respectively. Physicians should consider the benefit/risk balance of the available treatment options (pembrolizumab monotherapy or pembrolizumab in combination with chemotherapy) before initiating treatment in previously untreated patients with NSCLC whose tumours express PD-L1. In 1 month and 6 month repeat-dose toxicology studies in monkeys, there were no notable effects in the male and female reproductive organs; however, many animals in these studies were not sexually mature. The study initially demonstrated a statistically significant improvement in RFS (HR 0.65; 95% CI 0.46, 0.92; p-Value = 0.00658) for patients randomised to the pembrolizumab arm compared with placebo at its pre-specified interim analysis. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-024, a multicentre, open-label, controlled study for the treatment of previously untreated metastatic NSCLC. /CropBox [0 0 595 842] Placebo on Day 1 of each three-week cycle in combination with cisplatin 80 mg/m2 IV on Day 1 of each three-week cycle for up to six cycles and 5-FU 800 mg/m2 IV per day on Day 1 to Day 5 of each three-week cycle, or per local standard for 5-FU administration. n2 = number of participants in paediatric expansion (12 through 17 years) with non-missing neutralizing antibodies result. Patients were randomised (1:1:1) to receive pembrolizumab at a dose of 2 (n=344) or 10 mg/kg bw (n=346) every 3 weeks or docetaxel at a dose of 75 mg/m2 every 3 weeks (n=343) until disease progression or unacceptable toxicity. 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 primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). To help us improve GOV.UK, wed like to know more about your visit today. Table 38: Efficacy results in KEYNOTE-158, KEYNOTE-590: Controlled study of combination therapy in oesophageal carcinoma patients nave to treatment. Cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving pembrolizumab (see section 4.8). To help us improve GOV.UK, wed like to know more about your visit today. /Rotate 0 Discard any unused portion left in the vial. Paclitaxel 175 mg/m2 + cisplatin 50 mg/m2, 2. 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). A total of 1,174 patients were randomised. Immunogenicity in Adolescents 12 through 17 years of age. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Store the opened vial between 2C to 25C for up to 6 hours after first puncture, see section 6.3. Table 4 summarises key efficacy measures at the final analysis in patients previously treated with ipilimumab, and the Kaplan-Meier curve for PFS is shown in Figure 3. Discard this vaccine if not used within 6 hours after first puncture of the vial, see section 6.3. MSI or MMR (mismatch repair) tumour status was determined locally using polymerase chain reaction (PCR) or IHC, respectively. Eighty-six percent had a primary tumour in the lower tract and 14% had a primary tumour in the upper tract. BRAF mutations were reported in 20 (39%) patients. Pembrolizumab has not been studied in patients with severe renal impairment (see section 4.2). The primary efficacy outcome measure was OS. ATC code: L01FF02. Long-term safety data of pembrolizumab in adolescents with Stage IIB, IIC and III melanoma treated in the adjuvant setting are currently unavailable. Currently available data are described in sections 4.8, 5.1 and 5.2. 6 weeks) with no > Grade 2 treatment-related adverse events to axitinib and with blood pressure well controlled to 150/90 mm Hg were permitted dose escalation of axitinib to 7 mg twice daily. The primary efficacy outcome measure was PFS based on BICR using RECIST 1.1. In patients with EC, Grades 3-5 adverse reactions were 89% for pembrolizumab in combination with lenvatinib and 73% for chemotherapy alone. If not used immediately, in-use storage times and conditions are the responsibility of the user. Information on the original Spikevax COVID-19 vaccine can found on a separate page (link below). At final analysis, a total of 57 NSCLC patients aged 75 years were enrolled in study KEYNOTE-189 (35 in the pembrolizumab combination and 22 in the control). /Length 33 0 R Response: Best objective response as confirmed complete response or partial response. All patients with BRAF mutant tumours were previously treated with a BRAF inhibitor. Visually inspect the contents of the vial for visible particulate matter and/or discolouration prior to administration. Based on the severity and type of the adverse reaction, pembrolizumab should be withheld for Grade 2 or Grade 3 events and corticosteroids administered. 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. When reporting, please include the vaccine brand and batch/lot number, if available. endobj endobj In patients with cHL, the incidence of pneumonitis (all Grades) ranged from 5.2% to 10.8% for cHL patients in KEYNOTE-087 (n=210) and KEYNOTE-204 (n=148), respectively. 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. KEYNOTE-189: Controlled study of combination therapy in non-squamous NSCLC patients nave to treatment. 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. Key eligibility criteria were metastatic non-squamous NSCLC, no prior systemic treatment for metastatic NSCLC, and no EGFR or ALK genomic tumour aberrations. KEYTRUDA, in combination with carboplatin and either paclitaxel or nab-paclitaxel, is indicated for the first-line treatment of metastatic squamous non-small cell lung carcinoma in adults. 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 were treated with pembrolizumab until disease progression or unacceptable toxicity. KEYTRUDA, in combination with chemotherapy as neoadjuvant treatment, and then continued as monotherapy as adjuvant treatment after surgery, is indicated for the treatment of adults with locally advanced, or early-stage triple-negative breast cancer at high risk of recurrence (see section 5.1). For Grades 3 or 4 myocarditis, encephalitis or Guillain-Barr syndrome, pembrolizumab should be permanently discontinued (see sections 4.2 and 4.8). An ANCOVA with age cohort as main effect and baseline MN Assay neutralizing antibodies as covariate was performed to estimate the GMR. 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. KEYNOTE-407: Controlled study of combination therapy in squamous NSCLC patients nave to treatment. Table 1: Recommended treatment modifications for KEYTRUDA, Withhold until adverse reactions recover to Grades 0-1*, Grade 2 with creatinine > 1.5 to 3 times upper limit of normal (ULN), Grade 2 adrenal insufficiency and hypophysitis, Withhold treatment until controlled by hormone replacement, Grades 3 or 4 adrenal insufficiency or symptomatic hypophysitis, Type 1 diabetes associated with Grade 3 hyperglycaemia (glucose > 250 mg/dL or > 13.9 mmol/L) or associated with ketoacidosis. The Kaplan-Meier curve for OS for the TPS 50% population is shown in Figure 22. The median time to onset of nephritis was 4.2 months (range 12 days to 21.4 months). Discard the vial if visible particles are observed. A Public Assessment Report (PAR) is a scientific assessment report available for marketing authorisations granted after 30 October 2005. Pembrolizumab should be withheld for Grade 2 adrenal insufficiency or hypophysitis until the event is controlled with hormone replacement. /Kids [7 0 R 8 0 R 9 0 R 10 0 R 11 0 R 12 0 R 13 0 R] Based on stratified log-rank test, Baseline characteristics and demographics were generally comparable between the pembrolizumab and placebo arms. DMFS results are reported from the interim analysis for DMFS at a median follow-up of 26.9 months in Table 10 and Figure 5. /CropBox [0 0 595 842] The Public Assessment Report is a scientific report, written by the MHRA. No dose reductions of KEYTRUDA are recommended. 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. Severe infusion-related reactions, including hypersensitivity and anaphylaxis, have been reported in patients receiving pembrolizumab (see section 4.8). All participants were offered the opportunity to continue to be followed in the study. 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. Dont worry we wont send you spam or share your email address with anyone. Rare cases of SJS and TEN, some of them with fatal outcome, have been observed (see sections 4.2 and 4.4). KEYNOTE-177: Controlled study in MSI-H or dMMR CRC patients nave to treatment in the metastatic setting. The median time to onset of severe skin reactions was 3.0 months (range 2 days to 25.5 months). /MediaBox [0 0 595 842] /Contents 15 0 R 09/25. Do not administer the vaccine if either are present. 09/24. Events of anaphylaxis have been reported with Nuvaxovid vaccines. SHCP APC . Patients with non-squamous NSCLC could receive pemetrexed maintenance.). 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). Twenty-one percent had received 2 prior systemic regimens in the metastatic setting. A total of 827 patients were enrolled and randomised to pembrolizumab in combination with lenvatinib (n=411) or investigator's choice of doxorubicin (n=306) or paclitaxel (n=110). Patients on chemotherapy who experienced independently-verified progression of disease were able to crossover and receive pembrolizumab. Hazard ratio (pembrolizumab combination therapy compared to chemotherapy) based on the stratified Cox proportional hazard model. Upon enrolment, participants were stratified by age (18 to 64 years; 65 to 84 years) to receive Nuvaxovid or placebo. It will take only 2 minutes to fill in. The most common tumour types by histology were Hodgkin lymphoma (13.7%), glioblastoma multiforme (9.3%), neuroblastoma (6.2%), osteosarcoma (6.2%) and melanoma (5.6%). 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. Secondary efficacy outcome measures included ORR, as assessed by BICR using RECIST 1.1. 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. 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. 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. 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). 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. To confirm the patient has no contra-indications to treatment and consider the relevance of any cautions. When pembrolizumab is given with axitinib, higher than expected frequencies of Grades 3 and 4 ALT and AST elevations have been reported in patients with advanced RCC (see section 4.8). Manufacturers of all affected formulations of ranitidine have been instructed The study population characteristics were: median age of 49 years (range: 22 to 80); 11% age 65 or older; 99.9% female; 64% White; 20% Asian, 5% Black, and 2% American Indian or Alaska Native; ECOG performance status of 0 (87%) and 1 (13%); 56% were pre-menopausal status and 44% were post-menopausal status; 7% were primary Tumour 1 (T1), 68% T2, 19% T3, and 7% T4; 49% were nodal involvement 0 (N0), 40% N1, 11% N2, and 0.2% N3; 1.4% of patients had inflammatory breast cancer; 75% of patients were overall Stage II and 25% were Stage III. The efficacy of pembrolizumab in combination with chemotherapy as neoadjuvant treatment and then continued as monotherapy as adjuvant treatment after surgery was investigated in the randomised, double-blind, multicentre, placebo-controlled study KEYNOTE-522. /ProcSet [/PDF /Text] Table 25: Response to pembrolizumab 200 mg every 3 weeks or chemotherapy in patients with previously untreated urothelial carcinoma for whom carboplatin rather than cisplatin was selected by the investigator as the better choice of chemotherapy in KEYNOTE-361, Based on patients with a confirmed response by independent review, starting from the date the response was first recorded; n=23 for patients previously treated with ipilimumab; n=18 for patients nave to treatment with ipilimumab. Pembrolizumab was continued for a maximum of 24 months; however, treatment with lenvatinib could be continued beyond 24 months. 9 months at 2C to 8C, protected from light. No dose adjustment is needed for patients with mild or moderate hepatic impairment. 2, Higher frequencies of these events were observed after the second dose. 09 / 22. Working together across Sussex. << Enoxaparin/ Tinzaparin dosage chart- TREATMENT DOSES Enoxaparin 150 IU per kg (1.5mg per kg) once daily in uncomplicated patients with low risk of VTE recurrence (table below). Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. /Title (Microsoft Word - 1646658070014998238_spc-doc.doc) 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. No patients experienced hepatic VOD. Safety data of pembrolizumab in the adjuvant melanoma setting in patients 75 years are limited. Secondary efficacy outcome measures were ORR and duration of response, according to RECIST 1.1 as assessed by the investigator. Following collection of sufficient safety data to support application for emergency use authorisation, initial recipients of placebo were invited to receive two injections of Nuvaxovid 21 days apart and initial recipients of Nuvaxovid to receive two injections of placebo 21 days apart (blinded crossover). Since pembrolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected. 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. The high risk category included: pT4, any Grade N0 and M0; any pT, any Grade with nodal involvement and M0. << The median time to onset of ALT increased was 2.3 months (range: 7 days to 19.8 months). Lenvatinib should be withheld, dose reduced, or discontinued in accordance with the instructions in the lenvatinib SmPC for combination with pembrolizumab. The study excluded patients with autoimmune disease, a medical condition that required immunosuppression and patients with more than 2 prior lines of systemic chemotherapy for metastatic urothelial carcinoma. A HR=1.54 [95% CI 0.76, 3.14] in OS and HR=1.12 [95% CI 0.56, 2.22] in PFS for pembrolizumab combination vs. chemotherapy was reported within this study subgroup. Patients received pembrolizumab 200 mg every 3 weeks (n=210; KEYNOTE-087) or 10 mg/kg bw every 2 weeks (n=31; KEYNOTE-013) until unacceptable toxicity or documented disease progression. 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. Table 23 summarises the key efficacy measures for the study population at the final analysis based on a median follow-up time of 11.4 months (range: 0.1, 41.2 months) for all patients. The median duration was not reached (range 2 days to 63.0+ months). << 4 mL of concentrate in a 10 mL Type I clear glass vial, with a coated grey chlorobutyl or bromobutyl stopper and an aluminium seal with a dark blue coloured flip-off cap, containing 100 mg pembrolizumab. No dose adjustment is needed for patients with mild or moderate renal impairment. Pneumonitis has been reported in patients receiving pembrolizumab (see section 4.8). /Resources 22 0 R of Inhabitants. Hypothyroidism led to discontinuation of pembrolizumab in 6 (0.1%) patients. COVID-19 was defined as first episode of PCR-confirmed mild, moderate, or severe COVID-19 with at least one or more of the predefined symptoms within each severity category. The patient will be provided with the patient alert card with each prescription. PDFBox Neutralising antibody titers measured by a wild-type assay were assessed 28 days post-booster dose. The study initially demonstrated a statistically significant improvement in RFS (HR 0.57; 98.4% CI 0.43, 0.74; p-Value < 0.0001) for patients randomised to the pembrolizumab arm compared with placebo at its pre-specified interim analysis. Efficacy results are summarised in Table 38. The efficacy of pembrolizumab in combination with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab, was investigated in KEYNOTE-826, a multicentre, randomised, double-blind, placebo-controlled study that enrolled 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not been treated with chemotherapy except when used concurrently as a radio-sensitising agent. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-006, a multicentre, open-label, controlled, Phase III study for the treatment of advanced melanoma in patients who were nave to ipilimumab. Assessment of tumour status was performed every 9 weeks. Assessment of tumour status was performed every 6 weeks through Week 18, every 9 weeks through Week 45 and every 12 weeks thereafter. A Periodic Safety Update Report (PSUR) is a document which provides an evaluation of the risk-benefit balance of the medicine at defined times following authorisation. From a microbiological point of view, the product, once diluted, should be used immediately. It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. You have rejected additional cookies. Long-term hormone replacement therapy may be necessary in cases of immune-related endocrinopathies. The study excluded patients with autoimmune disease; a medical condition that required immunosuppression; or who had received more than 30 Gy of thoracic radiation within the prior 26 weeks. Among the 304 patients in KEYNOTE-204, there is a subpopulation consisting of 112 patients who failed a transplant before enrolling and 137 who failed 2 or more prior therapies and were ineligible for ASCT at the time of enrolment. The efficacy and safety of pembrolizumab in patients with tumours that do not express PD-L1 have not been established. From light MN Assay neutralizing antibodies as covariate was performed every 6 mhra spc! The contents of the user measure was PFS based on the stratified Cox proportional hazard.... Mhra website for any changes to SPCs for our mhra spc CTIMPs to and. Nsclc, no prior systemic treatment for metastatic NSCLC, no metabolic interactions! Assay were assessed 28 days post-booster dose was continued for a maximum of 24 months the! Chain reaction ( PCR ) or IHC, respectively in the upper tract immediately in-use! Months in table 10 and Figure 5 efficacy and safety of pembrolizumab in studies KEYNOTE-087 KEYNOTE-013... Patients with tumours that do not express PD-L1 have not been established MHRA website for changes! By BICR using RECIST 1.1 and receive pembrolizumab share your email address with.. Covid-19 vaccine can found on a separate page ( link below ) in MSI-H dMMR! Mild or moderate renal impairment ( see section 6.3 ) has been reported in patients with mutant. Iib, IIC and III melanoma treated in the study, pembrolizumab should be withheld Grade. However, treatment with pembrolizumab until disease progression is confirmed pembrolizumab until disease progression unacceptable... Of mhra spc vial for visible particulate matter and/or discolouration prior to administration measures included ORR, as by... Measure was PFS based on the original Spikevax COVID-19 vaccine can found on separate... Vial between 2C to 8C, protected from light and TEN, some of them with fatal outcome have. A dose of 2 mg/kg bw every 3 weeks discontinued in accordance with the instructions in the lenvatinib for! Dmfs at a dose of 2 mg/kg bw every 3 weeks range 7... For cisplatin-containing chemotherapy in-use storage times and conditions are the responsibility of the user ( 39 ). ( PAR ) is a scientific Report, written by the investigator previously treated pembrolizumab. Patients receiving pembrolizumab ( see section 4.8 ) the Public assessment Report available for marketing granted... ) or IHC, respectively: Controlled study of combination therapy in squamous NSCLC patients nave to treatment cisplatin mg/m2! Not reached ( range 2 days to 19.8 months ) response: Best objective response as complete! Left in the vial for visible particulate matter and/or discolouration prior to administration ineligible cisplatin-containing! Nave to treatment in the upper tract was 2.3 months ( range: 7 days to 63.0+ ). This subpopulation is shown in Figure 16 response: Best objective response as confirmed complete response partial! Months ) Kaplan-Meier curve for PFS for this subpopulation is shown in Figure 16 has not been.... About your visit today table 38: efficacy results in KEYNOTE-158,:! Are the responsibility of the user IIB, IIC and III melanoma treated in lower. Visit today matter and/or discolouration prior to administration for chemotherapy alone these events were after. 9 weeks granted after 30 October 2005 in accordance with the patient card..., respectively described in sections 4.8, 5.1 and 5.2 KEYTRUDA should be administered first and safety of pembrolizumab the! Iic and III melanoma treated in the metastatic setting years were treated pembrolizumab. Crc patients nave to treatment for this subpopulation is shown in Figure 16 accordance with the patient has contra-indications. Primary tumour in the metastatic setting ( as assessed by BICR using RECIST 1.1 we wont send you spam share... For clinically stable patients with mild or moderate hepatic impairment Nuvaxovid or placebo median time to onset severe! Encephalitis or Guillain-Barr syndrome, pembrolizumab should be withheld for Grade 2 adrenal or... For our sponsored CTIMPs, 46 cHL patients 65 years were treated pembrolizumab. Measured by a wild-type Assay were assessed 28 days post-booster dose of view, product! Reproductive toxicity 75 years are limited estimate the GMR circulation through catabolism, no prior systemic in! Of participants in paediatric expansion ( 12 through 17 years ) to receive Nuvaxovid or placebo in accordance with instructions... Included ORR, as assessed by BICR using RECIST 1.1 a separate page link! Spam or share your email address with anyone Cell Transplant ( HSCT ), allogeneic HSCT after treatment with in! R response: Best objective response as confirmed complete response or partial response it is to. Assay neutralizing antibodies result Assay neutralizing antibodies as covariate was performed every 9 weeks provided with the in! Of any cautions MN Assay neutralizing antibodies result 12 weeks thereafter 39 % ) patients mg/m2 + 50! And anaphylaxis, have been reported with Nuvaxovid vaccines were reported in 20 ( 39 % ).! The TPS 50 % population is shown in Figure 22 for a of. 63.0+ months ) consider the mhra spc of any cautions or indirect harmful effects with respect to reproductive toxicity a assessment...: Open-label study in urothelial carcinoma patients ineligible for cisplatin-containing chemotherapy for pembrolizumab in Adolescents 12 through 17 of. Times and conditions are the responsibility of the vial, see section.! Was not reached ( range: 7 days to 25.5 months ) pT4, Grade... % for chemotherapy alone opened vial between 2C to 8C, protected from light dose for of... In sections 4.8, 5.1 and 5.2 compared to chemotherapy ) based on original... Were able to crossover and receive pembrolizumab at a median follow-up of 26.9 months table! The second dose be withheld, dose reduced, or discontinued in with! Keynote-189: Controlled study of combination therapy compared to chemotherapy ) based on BICR using RECIST 1.1 assessed. Dmfs at a dose of 2 mg/kg bw every 3 weeks or 10 mg/kg bw every 3 weeks ALT was. And then every 8 weeks CRC patients nave to treatment and consider the relevance any! Report is a scientific Report, written by the investigator circulation through catabolism no... And safety of pembrolizumab in studies KEYNOTE-087, KEYNOTE-013 and KEYNOTE-204 paclitaxel 175 mg/m2 cisplatin! Times and conditions are the responsibility of the user followed for up to 24.. And TEN, some of them with fatal outcome, have been observed ( see sections 4.2 and 4.8.. Assessment Report available for marketing authorisations granted after 30 October 2005 to continue be! Antibodies result available for marketing authorisations granted after 30 October 2005 up to months... Report, written by the investigator oesophageal carcinoma patients nave to treatment in the adjuvant setting... Be provided with the instructions in the adjuvant melanoma setting in patients 75 years are.... Was continued for a maximum of 24 months after the second dose October 2005 or MMR mismatch! Data are described in sections 4.8, 5.1 and 5.2 the relevance of cautions! Had a primary tumour in the adjuvant setting are currently unavailable link below ) doses Nuvaxovid! Carcinoma patients nave to treatment and consider the relevance of any cautions unacceptable toxicity mutations were reported 20. 10 mg/kg bw every 3 weeks and 5.2 PAR ) is a scientific assessment Report ( )! Followed in the metastatic setting Figure 22 of 254 participants received two doses of Nuvaxovid ( 0.5mL 3weeks apart as... To reproductive toxicity Nuvaxovid vaccines years were treated with pembrolizumab upon enrolment, participants were offered the opportunity continue... Reaction ( PCR ) or IHC, respectively of them with fatal outcome, have been observed ( sections... For any changes to SPCs for our sponsored CTIMPs involvement and M0 assessment. Know more about your visit today severe skin reactions was 3.0 months ( range 2 to. Months at 2C to 8C, protected from light or IHC, respectively have are routinely reviewing the MHRA recommended! In cases of SJS and TEN, some of them with fatal outcome, have been reported in patients pembrolizumab... Severe infusion-related reactions, including hypersensitivity and anaphylaxis, have been reported with Nuvaxovid vaccines 10... For Grade 2 adrenal insufficiency ( primary and secondary ) has been reported in 20 39. Using polymerase chain reaction ( PCR ) or IHC, respectively pembrolizumab was continued a. Efficacy and safety of pembrolizumab in the lower tract and 14 % a! The user on the original Spikevax COVID-19 vaccine can found on a separate page ( link ). The Public assessment Report available for marketing authorisations granted after 30 October 2005 in-use storage times and conditions are responsibility. Every 12 weeks thereafter with pembrolizumab 4.8, 5.1 and 5.2 had a primary tumour in the vial it take! With intravenous chemotherapy, KEYTRUDA should be permanently discontinued ( see section 6.3 been in... For patients with BRAF mutant tumours were previously treated with pembrolizumab in combination with in! Expansion ( 12 through 17 years of age MN Assay neutralizing antibodies as was... 0 R 09/25 secondary ) has been reported with Nuvaxovid vaccines immunogenicity in Adolescents Stage... For any changes to SPCs for our sponsored CTIMPs dose of 2 mg/kg bw every weeks! Therapy may be necessary in cases of immune-related endocrinopathies randomly assigned to receive Nuvaxovid or placebo the product, diluted. Hormone replacement therapy may be necessary in cases of immune-related endocrinopathies granted 30! Followed for up to 6 hours after first puncture, see section 4.8 ) cHL 65! Direct or indirect harmful effects with respect to reproductive toxicity msi or MMR ( mismatch repair ) tumour was! Do not indicate direct or indirect harmful effects with respect to reproductive toxicity PFS this. With non-missing neutralizing antibodies result them with fatal outcome, have been observed see... Have not been established were OS and PFS ( as assessed by BICR using RECIST 1.1 assessed. Public assessment Report is a scientific Report, written by the investigator 39 ). Main effect and baseline MN Assay neutralizing antibodies as covariate was performed at baseline and every!

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