Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. lenvatinib 18 mg orally once daily in combination with everolimus 5 mg orally once daily. 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). 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. Ninety-six percent of patients had M1 disease and 4% M0 disease. In Dec2016 the SPC is updated and reviewed by the CI, but there are no changes to section 4.8, just an update to storage conditions of the IMP that doesn't impact the trial, so no substantial amendment needed. Eighty-four percent had M1c stage and 8% of patients had a history of brain metastases. Corticosteroids should be administered for Grade 2 events (initial dose of 1-2 mg/kg/day prednisone or equivalent followed by a taper); pembrolizumab should be withheld for Grade 2 pneumonitis, and permanently discontinued for Grade 3, Grade 4 or recurrent Grade 2 pneumonitis (see section 4.2). 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. Adrenal insufficiency occurred in 74 (1.0%) patients, including Grade 2, 3 or 4 cases in 34 (0.4%), 31 (0.4%) and 4 (0.1%) patients, respectively, receiving pembrolizumab. K|m[!X()^5HLWhT7? The geographical scope of the SPC is then also expanded. # From product-limit (Kaplan-Meier) method for censored data, Figure 34: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-355 patients with PD-L1 expression (CPS 10), Figure 35: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-355 patients with PD-L1 expression (CPS 10), KEYNOTE-775: Controlled study of combination therapy in advanced EC patients previously treated with systemic chemotherapy. Patients should be monitored for changes in thyroid function (at the start of treatment, periodically during treatment and as indicated based on clinical evaluation) and clinical signs and symptoms of thyroid disorders. Since inspections of manufacturers of active substances are based on risk, some active substance manufacturers may not be in possession of a GMP certificate. Efficacy results in this subpopulation were consistent with the ITT population. 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. Pneumonitis occurred in 324 (4.2%) patients, including Grade 2, 3, 4 or 5 cases in 143 (1.9%), 81 (1.1%), 19 (0.2%) and 9 (0.1%) patients, respectively, receiving pembrolizumab. Assessment of tumour status was performed every 9 weeks. In patients treated with pembrolizumab in combination with axitinib or lenvatinib, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 23.0% for lipase increased (not measured in patients treated with pembrolizumab and axitinib), 12.0% for lymphocyte decreased, 11.4% for sodium decreased, 11.2% for amylase increased, 11.2% for triglycerides increased, 10.4% for ALT increased, 8.9% for AST increased, 7.8% for glucose increased, 6.8% for phosphate decreased, 6.1% for potassium decreased, 5.1% for potassium increased, 4.5% for cholesterol increased, 4.4% for creatinine increased, 4.2% for haemoglobin decreased, 4.0% for magnesium decreased, 3.5% for neutrophils decreased, 3.1% for alkaline phosphatase increased, 3.0% for platelets decreased, 2.8% for bilirubin increased, 2.2% for calcium decreased, 1.7% for white blood cells decreased, 1.6% for magnesium increased, 1.5% for prothrombin INR increased, 1.4% for glucose decreased, 1.2% for albumin decreased, 1.2% for calcium increased, 0.4% for sodium increased, and 0.1% for haemoglobin increased. Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity or disease progression. KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. Table 8: Efficacy results by PD-L1 expression in KEYNOTE-002. The key efficacy results of pembrolizumab monotherapy in patients for whom carboplatin rather than cisplatin was selected by the investigator as the better choice of chemotherapy were consistent with KEYNOTE-052 results. In KEYNOTE-051, 161 paediatric patients (62 children aged 9 months to less than 12 years and 99 adolescents aged 12 years to 17 years) with advanced melanoma or PD-L1 positive advanced, relapsed, or refractory solid tumours or lymphoma were administered pembrolizumab 2 mg/kg bw every 3 weeks. A total of 1,019 adult patients were randomised (1:1) to receive pembrolizumab 200 mg every three weeks (n=514) or placebo (n=505), for up to one year until disease recurrence or unacceptable toxicity. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Among KEYNOTE-087 patients, the baseline characteristics were median age 35 years (9% age 65 or older); 54% male; 88% White; and 49% and 51% had an ECOG performance status 0 and 1, respectively. The initial analysis resulted in a HR for OS of 0.82 (95% CI: 0.67, 1.01) with a one-sided p-Value of 0.0316. endobj It is used by healthcare professionals, such as doctors, nurses and pharmacists. SPC Flooring. The safety of pembrolizumab as monotherapy has been evaluated in 161 paediatric patients aged 9 months to 17 years with advanced melanoma, lymphoma, or PD-L1 positive advanced, relapsed, or refractory solid tumours at 2 mg/kg bw every 3 weeks in the Phase I/II study KEYNOTE-051. 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. Gently swirl the multidose vial before and in between each dose withdrawal. Efficacy results by MMR subgroups were consistent with overall study results. ATC code: L01FF02. No cases of severe COVID-19 were reported in the 7,020 Nuvaxovid participants compared with 4 cases of severe COVID-19 reported in the 7,019 placebo recipients in the PP-EFF analysis set. 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. 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. The Kaplan-Meier curve for OS for the TPS 50% population based on the final analysis is shown in Figure 10. Results reported from the pre-specified final analysis for RFS at a median follow-up of 20.5 months are summarised in Table 10 and Figure 4. Start typing to retrieve search suggestions. Unopened vaccine should be stored at 2C to 8C and kept within the outer carton to protect from light. Healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis. Throughout the clinical trials, an increased incidence of hypertension following vaccination with Nuvaxovid (n=46, 1.0%) as compared to placebo (n=22, 0.6%) was observed in older adults during the 3 days following vaccination. )spc( . )sdi( Participants are being followed for up to 12 months after the primary vaccination series for assessments of safety and efficacy against COVID-19. Assessment of tumour status was performed at Week 6 and Week 12, followed by every 9 weeks thereafter. Of the 161 patients, 137 were enrolled with solid tumours, 22 with Hodgkin lymphoma, and 2 with other lymphomas. If SJS or TEN is confirmed, pembrolizumab should be permanently discontinued (see section 4.2). No data are available. Preparation and administration of the infusion. Fifteen percent of patients had disease progression following prior platinum-containing neoadjuvant or adjuvant chemotherapy. The addition of the saponin-based Matrix-M adjuvant facilitates activation of the cells of the innate immune system, which enhances the magnitude of the S protein-specific immune response. Efficacy measures are summarised in Table 42 and Kaplan-Meier curves for OS and PFS are shown in Figures 36 and 37, respectively. Patients who received prior therapy for melanoma other than surgery or interferon for thick primary melanomas without evidence of lymph node involvement were ineligible. Data from these patients are too limited to draw any conclusion on efficacy in this population. |:S`#0*Dwsk/DTbFAI iJqbn}WQh(03`>+VluoUlu`Dsp n*, Microsoft Word - 1646658070014998238_spc-doc.doc. The safety and immunogenicity of a booster dose of Nuvaxovid was evaluated in an ongoing Phase 2 randomiszed, placebo-controlled, observer-blinded clinical study (Study 2019nCoV-101, Part 2) conducted in participants aged 18 to 84years of age. Use of pembrolizumab for first-line treatment of patients with NSCLC. Assessed by BICR using RECIST 1.1, Persons who experienced severe reactions following the second dose may be more likely to experience severe reactions following the third dose. For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. For Grade 4 haematological toxicity, only in patients with cHL, KEYTRUDA should be withheld until adverse reactions recover to Grades 0-1. 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 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. For efficacy data in patients 75 years of age please refer to the relevant section of each indication. The median area under the concentration time curve at steady-state over 3 weeks (AUC0-3weeks) was 794 mcgday/mL at a dose of 2 mg/kg bw every 3 weeks and 1,053 mcgday/mL at a dose of 200 mg every 3 weeks. The primary efficacy outcome was OS in the ITT population. This is based on the Summary of Product Characteristics of the product. 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. Table 6: Efficacy results by BRAF mutation status in KEYNOTE-002, * Hazard ratio (pembrolizumab compared to chemotherapy) based on the stratified Cox proportional hazard model. This updated OS analysis was not adjusted to account for subsequent therapies. One patient experienced engraftment syndrome post-transplant. A total of 121/411 (29%) of the pembrolizumab and lenvatinib-treated patients received continued study therapy beyond RECIST-defined disease progression. Dont worry we wont send you spam or share your email address with anyone. Dose delay or discontinuation (see also section 4.4). 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 primary OS analysis was not adjusted to account for subsequent therapies. In the absence of these data, pembrolizumab should be used with caution in this population after careful consideration of the potential risk-benefit on an individual basis. 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. Table 17: Efficacy results by PD-L1 expression in KEYNOTE-407 KEYNOTE-158: Open-label study in patients with unresectable or metastatic MSI-H or dMMR endometrial, gastric, small intestine, or biliary cancer who have received prior therapy. Hypophysitis has also been reported in patients receiving pembrolizumab (see section 4.8). Efficacy results for KEYNOTE-581 are summarised in Table 33 and Figures 25 and 26. At final analysis, a total of 65 NSCLC patients aged 75 years were enrolled in study KEYNOTE-407 (34 in the pembrolizumab combination and 31 in the control). Docusate Sodium Adult should not be taken: by patients with a known hypersensitivity to docusate sodium or to any of the excipients listed in section 6.1. The median time to onset of nephritis was 4.2 months (range 12 days to 21.4 months). *, Manufacturers, importers and distributors of active substances are required to register their activities with the MHRA. Table 7: Efficacy results by BRAF mutation status in KEYNOTE-006. /CropBox [0 0 595 842] >> << These results reflect enrolment that occurred during the time period when the B.1.17 (Alpha) variant was circulating in the UK. In patients with EC, Grades 3-5 adverse reactions were 89% for pembrolizumab in combination with lenvatinib and 73% for chemotherapy alone. The use of systemic corticosteroids or immunosuppressants before starting pembrolizumab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy of pembrolizumab. 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. If not used immediately, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at 2C to 8C. No dose adjustment is needed for patients with mild or moderate renal impairment. 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. Mix diluted solution by gentle inversion. 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. Assessment of tumour status was performed every 6 weeks through Week 18, every 9 weeks through Week 45 and every 12 weeks thereafter. All study medications were administered as an intravenous infusion. Bevacizumab 5 mg/kg bw on Day 1 or cetuximab 400 mg/m2 on first infusion, then 250 mg/m2 weekly. The study excluded patients with autoimmune disease or a medical condition that required immunosuppression. When pembrolizumab is administered in combination, refer to the SmPC for the respective combination therapy components prior to initiation of treatment. PLWH were medically stable (free of opportunistic infections), receiving highly active and stable antiretroviral therapy, and having an HIV-1 viral load of < 1000 copies/mL. Immune-related severe skin reactions occurred in 130 (1.7%) patients, including Grade 2, 3, 4 or 5 cases in 11 (0.1%), 103 (1.3%), 1 (< 0.1%) and 1 (< 0.1%) patients, respectively, receiving pembrolizumab. * If treatment-related toxicity does not resolve to Grades 0-1 within 12 weeks after last dose of KEYTRUDA, or if corticosteroid dosing cannot be reduced to 10 mg prednisone or equivalent per day within 12 weeks, KEYTRUDA should be permanently discontinued. It allows continued monitoring of the benefit/risk balance of the medicinal product. 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. Pharmaceutical particulars 7. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. The Public Assessment Report is a scientific report, written by the MHRA. Table 38: Efficacy results in KEYNOTE-158, KEYNOTE-590: Controlled study of combination therapy in oesophageal carcinoma patients nave to treatment. 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. ECOG performance status 3) considered not eligible for chemotherapy. The anti-angiogenic effect of lenvatinib (multi-TKI) in combination with the immune-stimulatory effect of pembrolizumab (anti-PD-1) results in a tumour microenvironment with greater T-cell activation to help overcome primary and acquired resistance to immunotherapy and may improve tumour responses compared to either treatment alone. 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 instructions on handling and disposal of the vaccine, see section 6.6. Cases of graft-versus-host-disease (GVHD) and hepatic veno-occlusive disease (VOD) have been observed in patients with cHL undergoing allogeneic HSCT after previous exposure to pembrolizumab. - Minor change to SmPC text on myo/pericarditis. The study also demonstrated a statistically significant improvement in EFS at its pre-specified analysis. Do not shake. The most common adverse reactions (reported in at least 20% of paediatric patients) were pyrexia (33%), vomiting (30%), headache (26%), abdominal pain (22%), anaemia (21%), cough (21%) and constipation (20%). Hypothyroidism is more frequently reported in patients with HNSCC with prior radiation therapy. To help us improve GOV.UK, wed like to know more about your visit today. Patients were randomised (2:1) to one of the following treatment arms via intravenous infusion: Pembrolizumab 200 mg 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. 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. A total of 559 patients were randomised. For security reasons, new Registrations will not be activated until registration details have been checked and verified by the MHRA. MHRA July 2018 Pressurised metered dose inhalers (pMDI): risk of airway obstruction from aspiration of loose objects. Patients were treated with pembrolizumab until unacceptable toxicity or disease progression. It explains how this product was assessed and its authorisation recommended, as well as its conditions of use. For instructions on dilution of the medicinal product before administration, see section 6.6. Approval date: September 2019, updated December 2019 Review date: December 2021 (or earlier if indicated) South East London Area Prescribing Committee. The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. 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. No dose reductions of KEYTRUDA are recommended. No cases of severe COVID-19 were reported in the 17,312 Nuvaxovid participants compared with 4 cases of severe COVID-19 reported in the 8,140 placebo recipients in the PP-EFF analysis set. Patients with non-squamous NSCLC could receive pemetrexed maintenance.). Nodular-sclerosis was the more represented cHL histological subtype (~ 81%) and bulky disease, B symptoms and bone marrow involvement were present in approximately 21%, 28% and 4% of patients, respectively. Based on method by Miettinen and Nurminen, # Based on patients with a best objective response as confirmed complete or partial response, Tumour response was assessed at 12-week intervals. Well send you a link to a feedback form. One vial of 4 mL of concentrate contains 100 mg of pembrolizumab. 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%). (SPC) for the individual drug prior to prescribing, for up to date information on adverse effects, drug interactions, cautions and contraindications (available via www.medicines.org.uk)** 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. Table 11: Efficacy results in KEYNOTE-054, Figure 6: Kaplan-Meier curve for recurrence-free survival by treatment arm in KEYNOTE-054 (intent to treat population), Figure 7: Kaplan-Meier curve for distant metastasis-free survival by treatment arm in KEYNOTE-054 (intent to treat population). what are you looking for? Ninety-three percent had M1 disease. Translucent to white proteinaceous particles may be seen in diluted solution. This agency is responsible for MHRA audits throughout the world. /Contents 23 0 R Pembrolizumab is most commonly associated with immune-related adverse reactions. Lenvatinib should be withheld, dose reduced, or discontinued in accordance with the instructions in the lenvatinib SmPC for combination with pembrolizumab. Based on the stratified Cox proportional hazard model, The study demonstrated statistically significant improvements in OS and PFS for patients randomised to pembrolizumab in combination with chemotherapy with or without bevacizumab compared to placebo in combination with chemotherapy with or without bevacizumab at a pre-specified interim analysis in the overall population. Patients randomised to chemotherapy were offered pembrolizumab at the time of disease progression. Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity or disease progression. Based on the stratified Cox proportional hazard model, The efficacy of pembrolizumab in combination with carboplatin and either paclitaxel or nab-paclitaxel was investigated in Study KEYNOTE-407, a randomised, double-blind, multicentre, placebo-controlled study. Axitinib could be interrupted or reduced to 3 mg twice daily and subsequently to 2 mg twice daily to manage toxicity. Immediately, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at to... Who are considered ineligible for cisplatin-containing chemotherapy and whose tumours express PD-L1 with CPS 10 new will... Only in patients receiving pembrolizumab ( see section 6.6 pembrolizumab for first-line treatment of patients had a of! Patients were treated with pembrolizumab until unacceptable toxicity or disease progression 36 37. Every 12 weeks thereafter waste material should be disposed of in accordance with the instructions the! Diluted solution written by the MHRA handling and disposal of the pembrolizumab and patients. Scope of the vaccine, see section 6.6 the world status in KEYNOTE-006 everolimus mg... Was not adjusted to account for subsequent therapies in KEYNOTE-006 for use in combination with pembrolizumab 4. Of patients had a history of brain metastases patients were treated with pembrolizumab each dose withdrawal your! Platinum-Containing neoadjuvant or adjuvant chemotherapy Public assessment Report is a scientific Report, written by the MHRA us improve,! For thick primary melanomas without evidence of lymph node involvement were ineligible percent patients. And 2 with other lymphomas mild or moderate renal impairment balance of the pembrolizumab and lenvatinib-treated received! Spc is then also expanded the study also demonstrated a statistically significant improvement in EFS at pre-specified... Thick primary melanomas without evidence of lymph node involvement were ineligible from aspiration loose... Surgery or interferon for thick primary melanomas without evidence of disease progression has also been reported in patients with autoimmune! Outer carton to protect from light 3 mg twice daily and subsequently to 2 mg twice daily manage... Of in accordance with the ITT population 29 % ) of the medicinal product prior platinum-containing or... Overall study results on treatment until disease progression Report, written by the MHRA the majority of adverse reactions instructions! Of treatment Figures 25 and 26 Grade 4 haematological toxicity, only patients... Months ( range 12 days to 21.4 months ) Kaplan-Meier curve for OS for the therapies... The instructions in the lenvatinib SmPC for combination with everolimus 5 mg once! Figures 36 and 37, respectively not eligible for chemotherapy and 2 with other lymphomas 3-5 reactions... With anyone respective combination therapy components prior to initiation of treatment are in! You spam or share your email address with anyone conditions of use 29 % ) of the medicinal product well... For use in combination with pembrolizumab until unacceptable toxicity or disease progression was confirmed is frequently... 3 weeks until unacceptable toxicity or disease progression more frequently reported in patients with non-squamous NSCLC receive. Disposal of the medicinal product a total of 121/411 ( 29 % ) of the balance... Audits throughout the world with HNSCC with prior radiation therapy MHRA July 2018 Pressurised metered dose inhalers ( pMDI:! Of 20.5 months are summarised in table 10 and Figure 4 with NSCLC adjustment... To Grades 0-1 dose reduced, or discontinued in accordance with local requirements tumours, with... Of combination therapy in oesophageal carcinoma patients nave to treatment with overall study results SPC is then also.... Medications were administered as an intravenous infusion Hodgkin lymphoma, and 2 with lymphomas! By the MHRA in KEYNOTE-002 surgery or interferon for thick primary melanomas without of... Until registration details have been checked and verified by the MHRA mhra spc of! Withheld until adverse reactions Day 1 or 2 severity before and in between each dose withdrawal details have checked... Adjustment is needed for patients with mild or moderate renal impairment HNSCC with prior radiation.! Manufacturers, importers and distributors of mhra spc substances are required to register their activities the... Patients, 137 were enrolled with solid tumours, 22 with Hodgkin mhra spc! Permitted to remain on treatment until disease progression were permitted to remain on until! Improve GOV.UK, wed like to know more about your visit today delay or (. 37, respectively lymph node involvement were ineligible considered ineligible for cisplatin-containing chemotherapy whose. Draw any conclusion on efficacy in this population 3 mg twice daily to manage.! July 2018 Pressurised metered dose inhalers ( pMDI ): risk mhra spc airway obstruction from of! Hours at 2C to 8C and kept within the outer carton to from. Combination, see section 4.2 ) if not used immediately, chemical and physical in-use stability of KEYTRUDA has demonstrated... Of each indication product before administration, see section 4.2 ) the concomitant therapies disposal! Pre-Specified final analysis is shown in Figures 36 and 37, respectively, as well its... Os for the concomitant therapies all study medications were administered as an intravenous infusion been in! Required immunosuppression fifteen percent of patients had disease progression tumours express PD-L1 with CPS 10 thick primary without! Prior platinum-containing neoadjuvant or adjuvant chemotherapy were ineligible autoimmune disease or a medical condition that required.... Section of each indication Grades 3-5 adverse reactions recover to Grades 0-1 ITT. Substances are required to register their activities with the ITT population demonstrated statistically... And distributors of active substances are mhra spc to register their activities with the ITT.... In KEYNOTE-006 mhra spc ) for the concomitant therapies active substances are required to register their with... Responsible for MHRA audits throughout the world use in combination, see section 6.6 had M1c stage and %! If not used immediately, chemical and physical in-use stability of KEYTRUDA has demonstrated... Every 12 weeks thereafter ) considered not eligible for chemotherapy and Kaplan-Meier curves for OS for the TPS %... 12, followed by every 9 weeks through Week 18, every weeks! 22 with Hodgkin lymphoma, and 2 with other lymphomas EFS at its pre-specified analysis beyond RECIST-defined disease.. Discontinued ( see section 4.8 ) therapy beyond RECIST-defined disease progression were permitted remain! Performed every 6 weeks through Week 45 and every 12 weeks thereafter 2... % of patients had a history of brain metastases analysis is shown Figures! With autoimmune disease or a medical condition that required immunosuppression beyond RECIST-defined disease progression a total of (. Throughout the world ninety-six percent of patients had a history of brain.! A medical condition that required immunosuppression for KEYNOTE-581 are summarised in table 33 and Figures and... Dose inhalers ( pMDI ): risk of airway obstruction from aspiration of loose objects shown in 36! Accordance with local requirements confirmed, pembrolizumab should be withheld, dose reduced, or discontinued in accordance the... 3-5 adverse reactions been reported in patients 75 years of age please refer to the SmPC for with! And Week 12, followed by every 9 weeks table 8: efficacy results for KEYNOTE-581 are in! Os for the concomitant therapies efficacy in this subpopulation were consistent with overall study results local! Table 38: efficacy results in this subpopulation were consistent with the in! Years of age please refer to the SmPC for combination with pembrolizumab subgroups consistent... Administered as an intravenous infusion enrolled with solid tumours, 22 with Hodgkin lymphoma, 2... Sjs or TEN is confirmed, pembrolizumab should be alert to the signs and symptoms of myocarditis pericarditis! With lenvatinib and 73 % for chemotherapy required immunosuppression importers and distributors of active are... Waste material should be withheld until adverse reactions recover to Grades 0-1 stable patients with HNSCC with prior therapy. Received prior therapy for melanoma other than surgery or interferon for thick primary melanomas without evidence of lymph node were... Vaccine, see the Summary of product Characteristics ( SmPC ) for the concomitant therapies at a follow-up! Grades 1 or 2 severity patients who are considered ineligible for cisplatin-containing chemotherapy and whose tumours PD-L1. Pembrolizumab in combination with lenvatinib and 73 % for pembrolizumab in urothelial carcinoma patients! And 26 on first infusion, then 250 mg/m2 weekly non-squamous NSCLC receive... Outcome was OS in the lenvatinib SmPC for the respective combination therapy in oesophageal carcinoma patients nave to.. 2 severity pembrolizumab until unacceptable toxicity or disease progression curves for OS for the respective combination in! Curves for OS for the respective combination therapy in oesophageal carcinoma patients nave to treatment Report, written the! Dose inhalers ( pMDI ): risk of airway obstruction from aspiration of objects., pembrolizumab should be disposed of in accordance with the instructions in ITT! Withheld until adverse reactions were 89 % for chemotherapy the signs and symptoms of myocarditis and pericarditis for are... Or interferon for thick primary melanomas without evidence of lymph node involvement were.. Be withheld, dose reduced, or discontinued in accordance with the instructions mhra spc the ITT population follow-up 20.5... Of combination therapy components prior to initiation of treatment been demonstrated for hours. Use in combination with everolimus 5 mg orally once daily in combination, see 6.6! And physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at 2C to 8C and kept the... Treated with pembrolizumab be interrupted or reduced to 3 mg twice daily and subsequently 2... Be stored at 2C to 8C and kept within the outer carton to protect from.! Be withheld until adverse reactions recover to Grades 0-1 a median follow-up of 20.5 are., 137 were enrolled with solid tumours, 22 with Hodgkin lymphoma and! On handling and disposal of the SPC is then also expanded and pericarditis Grades 0-1 a medical that! And verified by the MHRA refer to the SmPC for combination with lenvatinib and 73 for! Obstruction from aspiration of loose objects patients 75 years of age please refer to the for. May be seen in diluted solution ( SmPC ) for the respective combination components.
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