Table 28: Efficacy results for pembrolizumab plus chemotherapy and pembrolizumab as monotherapy by PD-L1 expression in KEYNOTE-048 (CPS 20), 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. Table 14: Efficacy results in KEYNOTE-189, Pembrolizumab + Pemetrexed + Platinum Chemotherapy, Placebo + Pemetrexed + Platinum Chemotherapy, * A total of 113 patients (57%) who discontinued study treatment in the placebo plus chemotherapy arm crossed over to receive monotherapy pembrolizumab or received a checkpoint inhibitor as subsequent therapy, /CropBox [0 0 595 842] /Contents 25 0 R Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates for male and female participants and racial groups, and across participants with medical comorbidities associated with high risk of severe COVID-19. Of the 161 patients, 137 were enrolled with solid tumours, 22 with Hodgkin lymphoma, and 2 with other lymphomas. The efficacy of pembrolizumab in combination with lenvatinib was investigated in KEYNOTE-775, a randomised, multicentre, open-label, active-controlled study conducted in patients with advanced EC who had been previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including in the neoadjuvant and adjuvant settings. 17 0 obj Mix diluted solution by gentle inversion. /Pages 3 0 R Treatment with pembrolizumab or placebo continued until RECIST 1.1-defined progression of disease as determined by BICR, unacceptable toxicity, or a maximum of 24 months. 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. Efficacy in Adolescents 12 through 17 years of age. * The primary analysis of PFS included censoring for new anti-cancer treatment. Of these, 48 out of 61 (79%) were identified as Variants of Concern or Variants of Interest. Pharmaceutical form 4. The KEYNOTE-581 study was not powered to evaluate efficacy of individual subgroups. 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. Store the opened vial between 2C to 25C for up to 6 hours after first puncture, see section 6.3. 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. Patients should be monitored for hyperglycaemia or other signs and symptoms of diabetes. Such treatment It is unknown whether Nuvaxovid is excreted in human milk. Hyperthyroidism may be managed symptomatically. endobj Disease characteristics were squamous (18%) and non-squamous (82%); M1 (99%); and brain metastases (9%). The efficacy of pembrolizumab in combination with axitinib was investigated in KEYNOTE-426, a randomised, multicentre, open-label, active-controlled study conducted in patients with advanced RCC with clear cell component, regardless of PD-L1 tumour expression status and International Metastatic RCC Database Consortium (IMDC) risk group categories. Administration of pembrolizumab with lenvatinib was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered by the investigator to be deriving clinical benefit. Pembrolizumab is administered via the intravenous route and therefore is immediately and completely bioavailable. MHRA does not accept combined SmPCs covering, for example two different strengths of the same dosage form, but only accepts a single SmPC in the correct format using the relevant template . In patients with NSCLC, pneumonitis occurred in 8.9% with a history of prior thoracic radiation. The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. 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%). Patients with BRAF V600E mutant melanoma were not required to have received prior BRAF inhibitor therapy. Patients with the following conditions were excluded from clinical studies: active CNS metastases; ECOG PS 2 (except for urothelial carcinoma and RCC); HIV infection, hepatitis B or hepatitis C infection; active systemic autoimmune disease; interstitial lung disease; prior pneumonitis requiring systemic corticosteroid therapy; a history of severe hypersensitivity to another monoclonal antibody; receiving immunosuppressive therapy and a history of severe immune-related adverse reactions from treatment with ipilimumab, defined as any Grade 4 toxicity or Grade 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks. /Contents 27 0 R If rechallenging with axitinib, dose reduction as per the axitinib SmPC may be considered. Based on method by Miettinen and Nurminen, musculoskeletal pain (musculoskeletal discomfort, back pain, musculoskeletal stiffness, musculoskeletal chest pain and torticollis), cc. The concentrate is a clear to slightly opalescent, colourless to slightly yellow solution. 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. Great Britain. This updated OS analysis was not adjusted to account for subsequent therapies. 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). There was no statistically significant difference between pembrolizumab and chemotherapy in the final OS analysis in which 60% of the patients who had been randomised to receive chemotherapy had crossed over to receive subsequent anti-PD-1/PD-L1 therapies including pembrolizumab. No findings of toxicological significance were observed and the no observed adverse effect level (NOAEL) in both studies was 200 mg/kg bw, which produced exposure multiples of 19 and 94 times the exposure in humans at doses of 10 and 2 mg/kg bw, respectively. A subgroup analysis was performed as part of the final analysis of KEYNOTE-002 in patients who were PD-L1 positive (PD-L1 expression in 1% of tumour and tumour-associated immune cells relative to all viable tumour cells MEL score) vs. PD-L1 negative. Where we have identified any third party copyright information you will need to obtain permission from the copyright holders concerned. The efficacy of pembrolizumab was investigated in KEYNOTE-048, a multicentre, randomised, open-label, active-controlled study in patients with histologically confirmed metastatic or recurrent HNSCC of the oral cavity, pharynx or larynx, who had not previously received systemic therapy for recurrent or metastatic disease and who were considered incurable by local therapies. SHCP APC . Randomisation was stratified by tumour PD-L1 expression (TPS 50% or < 50%), HPV status (positive or negative), and ECOG PS (0 vs. 1). These results indicate a potential risk, based on its mechanism of action, that administration of pembrolizumab during pregnancy could cause foetal harm, including increased rates of abortion or stillbirth. In urothelial carcinoma, a higher number of deaths within 2 months was observed in pembrolizumab compared to chemotherapy (see section 5.1). Use of pembrolizumab in combination with chemotherapy. Seventy-five percent had a tumour histology of squamous cell carcinoma, and 25% had adenocarcinoma. This. 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. It is recommended to administer the second dose 3 weeks after the first dose (see section 5.1). The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions (see section 4.4). Assessed by BICR according to the IWG 2007 criteria by PET CT scans, Based on patients (n=150) with a response by independent review, Based on patients (n=18) with a response by independent review, # Based on Kaplan-Meier estimation; includes 62 patients with responses of 12 months or longer, Based on Kaplan-Meier estimation; includes 7 patients with responses of 12 months or longer, Based on Kaplan-Meier estimation; includes 37 patients with responses of 24 months or longer, Based on Kaplan-Meier estimation; includes 4 patients with responses of 60 months or longer. Example scenario - the approved RSI with the CTA was section 4.8 of SPC May2015. The median duration of follow-up was 70 days post-Dose 2, with 32,993 (66%) participants completing more than 2 months follow-up post-Dose 2. This medicinal product has been authorised under a so-called conditional approval scheme. BRAF mutations were reported in 302 (36%) patients. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who have received prior platinum-containing chemotherapy (see section 5.1). Response was assessed every 12 weeks, with the first planned post-baseline assessment at Week 12. Patients were enrolled regardless of tumour PD-L1 expression status. Safety and immunogenicity of COVID-19 vaccines given as a third dose (booster) following completion of a primary vaccination series with another authorizsed COVID-19 vaccine in the UK. The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). Data from these patients are too limited to draw any conclusion on efficacy in this population. Every medicine pack includes a patient information leaflet (PIL), which provides information on using the medicine safely. 2. Hyperthyroidism resolved in 315 (79.9%) patients, 11 with sequelae. 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. The median duration of the post-progression therapy was 2.8 months. In a clinical study of previously untreated patients with RCC receiving pembrolizumab in combination with axitinib, a higher than expected incidence of Grades 3 and 4 ALT increased (20%) and AST increased (13%) were observed. We use some essential cookies to make this website work. 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. Efficacy results by MMR subgroups were consistent with overall study results. All patients with BRAF mutant tumours were previously treated with a BRAF inhibitor. The primary efficacy analysis set (PP-EFF) included 2,770 participants who received either Nuvaxovid (n = 1,408) or placebo (n = 1,362), received two doses (Dose 1 on day 0; Dose 2 on day 21), did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infection through 7 days after the second dose. 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. Jevany, 28163 There were no notable effects in the male and female reproductive organs in monkeys based on 1-month and 6-month repeat-dose toxicity studies (see section 5.3). KEYTRUDA is for intravenous use. Reporting forms and information can be found at https://coronavirus-yellowcard.mhra.gov.uk or you can search for MHRA Yellow Card in the Google Play or Apple App Store. 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. To discuss the benefits and possible side-effects of treatment with the patient. The median number of prior lines of therapy administered for the treatment of cHL was 4 (range 1 to 12). 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. Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo. The safety of re-initiating pembrolizumab therapy in patients previously experiencing immune-related myocarditis is not known. The wholesale distribution of medicinal products and importation of medicines certified by a Qualified Person in accordance with Article 51 of Directive 2001/83/EC from listed countries is subject to the holding of a Wholesale Distribution Authorisation. The primary efficacy outcome measure was ORR as assessed by BICR using RECIST 1.1. It will take only 2 minutes to fill in. arthritis (joint swelling, polyarthritis and joint effusion), ee. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. Fifteen percent of patients had disease progression following prior platinum-containing neoadjuvant or adjuvant chemotherapy. Corticosteroid therapy may be considered. Participants may have received up to 2 platinum-containing therapies in total, as long as one was given in the neoadjuvant or adjuvant treatment setting. Among patients who were evaluable for PD-L1 expression (98%), 82% were PD-L1 positive and 18% were PD-L1 negative. In the event of an overdose, monitoring of vital functions and possible symptomatic treatment is recommended. Based on Miettinen and Nurminen method stratified by PD-L1 status, platinum chemotherapy and smoking status, Figure 11: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-189 (intent to treat population), Figure 12: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-189 (intent to treat population). Nuvaxovid may also be given as a booster dose in individuals 18 years of age and older following a primary series comprised of an mRNA vaccine or adenoviral vector vaccine (heterologous booster dose). The KEYNOTE-426 study was not powered to evaluate efficacy of individual subgroups. Based on best response of stable disease or better, Corticosteroids should be administered for Grade 2 events (initial dose of 1-2 mg/kg/day prednisone or equivalent followed by a taper) and, based on severity of creatinine elevations, pembrolizumab should be withheld for Grade 2, and permanently discontinued for Grade 3 or Grade 4 nephritis (see section 4.2). Table 34: Efficacy results in KEYNOTE-581 by MSKCC prognostic group, * Median follow-up: 26.5 months (data cutoff 28 August 2020), It will take only 2 minutes to fill in. We also use cookies set by other sites to help us deliver content from their services. It allows continued monitoring of the benefit/risk balance of the medicinal product. << Chemotherapy could continue per standard of care. Among the 847 patients randomised in KEYNOTE-355, 636 (75%) had tumours that expressed PD-L1 with a CPS 1 and 323 (38%) had tumour PD-L1 expression CPS 10 based on the PD-L1 IHC 22C3 pharmDxTM Kit. You can change your cookie settings at any time. We publish the most up-to-date information for a medicine according to its licence history. Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers. Nephritis occurred in 37 (0.5%) patients, including Grade 2, 3 or 4 cases in 11 (0.1%), 19 (0.2%) and 2 (< 0.1%) patients, respectively, receiving pembrolizumab as monotherapy. Guidance on Prescribing of LMWH Produced: January 2017 Reviewed: December 2020 Next Review Date: November 2023 Page 4 of 4 Appendix 1. Pembrolizumab should not be used during pregnancy unless the clinical condition of the woman requires treatment with pembrolizumab. 16 0 obj Administer the infusion solution intravenously over 30 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 to 5 m in-line or add-on filter. Study 3 is an ongoing Phase 2a/b, multicentre, randomised, observer-blinded, placebo-controlled study in HIV-negative participants 18 to 84 years of age and people living with HIV (PLWH) 18 to 64 years of age in South Africa. Vaccine efficacy is presented in Table 2. Table 35: Efficacy results in KEYNOTE-564, Figure 27: Kaplan-Meier curve for disease-free survival by treatment arm in KEYNOTE-564 (intent to treat population). Randomisation was stratified by tumour PD-L1 expression (TPS < 1% [negative] vs. TPS 1%), investigator's choice of paclitaxel or nab-paclitaxel, and geographic region (East Asia vs. non-East Asia). 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 or Grade 3 colitis, and permanently discontinued for Grade 4 or recurrent Grade 3 colitis (see section 4.2). Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and those who received placebo. 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. This is based on the Summary of Product Characteristics of the product. EIR Vinyl Flooring ZXE2001. A booster dose of Nuvaxovid (0.5 mL) may be administered intramuscularly approximately 6months after the primary series of Nuvaxovid in individuals 18years of age and older (homologous booster dose). 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). The M1 NED category included patients with metastatic disease who had undergone complete resection of primary and metastatic lesions. 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). Treatment with pembrolizumab continued until RECIST v1.1-defined progression of disease as determined by the investigator or unacceptable toxicity. Ninety-seven percent of the patients had M1 disease and 3% had M0 disease (locally advanced unresectable). Grades 3-5 adverse reactions in patients with RCC were 80% for pembrolizumab in combination with either axitinib or lenvatinib and 71% for sunitinib alone. KEYTRUDA, in combination with axitinib, is indicated for the first-line treatment of advanced renal cell carcinoma in adults (see section 5.1). 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. Seventy-six (47.2%) patients had 1 or more Grades 3 to 5 adverse reactions of which 5 (3.1%) patients had 1 or more adverse reactions that resulted in death. This page includes guidance for pharmaceutical companies and regulators on how to prepare and review summaries of product characteristics (SmPCs) for human medicines. Prior to dilution, the vial of liquid can be out of refrigeration (temperatures at or below 25C) for up to 24 hours. It explains how this product was assessed and its authorisation recommended, as well as its conditions of use. Patients were enrolled regardless of PD-L1 tumour expression status. Date of revision of the text Frequencies are defined as: very common ( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be estimated from the available data). The PD-1/PD-L1 pathway is thought to be involved in maintaining tolerance to the foetus throughout pregnancy. The potential risk of gastrointestinal perforation should be taken into consideration. 1. The Kaplan-Meier curve for EFS and OS are shown in Figures 32 and 33. Use of pembrolizumab for adjuvant treatment of patients with melanoma. 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%). Adrenal insufficiency (primary and secondary) has been reported in patients receiving pembrolizumab. News stories, speeches, letters and notices, Reports, analysis and official statistics, Data, Freedom of Information releases and corporate reports. Based on the severity of the adverse reaction, pembrolizumab should be withheld for Grade 3 skin reactions until recovery to Grade 1 or permanently discontinued for Grade 4 skin reactions, and corticosteroids should be administered (see section 4.2). The median duration was 3.3 months (range 6 days to 28.2+ months). A direct comparison of pembrolizumab when used in combination with lenvatinib to pembrolizumab monotherapy is not available. 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). Hypothyroidism resolved in 200 (21.3%) patients, 16 with sequelae. You have accepted additional cookies. KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of locally recurrent unresectable or metastatic triple-negative breast cancer in adults whose tumours express PD-L1 with a CPS 10 and who have not received prior chemotherapy for metastatic disease (see section 5.1). The median follow-up time in months was 37.3 (range: 0.1 to 65.2). The median time to onset of nephritis was 4.2 months (range 12 days to 21.4 months). what are you looking for? Of the pooled reactogenicity data, which includes participants aged 18 years and older enrolled in the two phase 3 studies who received any dose of Nuvaxovid (n=20,055) or placebo (n=10,561), the most frequent adverse reactions were injection site tenderness (75%), injection site pain (62%), fatigue (53%), myalgia (51%), headache (50%), malaise (41%), arthralgia (24%), and nausea or vomiting (15%). Updated RFS results at a median follow-up of 26.9 months were consistent with the final analysis for RFS for patients randomised to the pembrolizumab arm compared with placebo (HR 0.64; 95% CI 0.50, 0.84). Hypophysitis resolved in 15 patients, 8 with sequelae. Upon improvement to Grade 1, corticosteroid taper should be initiated and continued over at least 1 month. Gently swirl the multidose vial before and in between each dose withdrawal. /Type /Page >> Among the 5 adolescent participants with advanced melanoma treated on KEYNOTE-051, no patient had a complete or a partial response, and 1 patient had stable disease. Risk associated with intraneural injection: Accidental intraneural injection may lead the drug to move in retrograde manner along the nerve. included in other section of SPC. The companies those comply their GMP regulations can export their pharmaceutical products to UK. Use within 6 hours after first puncture. The key secondary outcome measure was OS. Nuvaxovid is administered intramuscularly as a course of 2 doses of 0.5 mL each. Table 39: Efficacy results for pembrolizumab plus chemotherapy in KEYNOTE-590 with PD-L1 expression (CPS 10), Patients with active autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. Each 0.5 mL dose is withdrawn into a sterile needle and sterile syringe to be administered by intramuscular injection, preferably in the deltoid muscle of the upper arm. /ProcSet [/PDF /Text] Continue typing to refine. Patients with Grades 1 or 2 infusion reaction may continue to receive pembrolizumab with close monitoring; premedication with antipyretic and antihistamine may be considered. In patients with cHL (n=389) the incidence of hypothyroidism was 17%, all of which were Grade 1 or 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 patients with HNSCC whose tumours express PD-L1 (see section 5.1). Based on Kaplan-Meier estimation, Figure 22: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-040 patients with PD-L1 expression (TPS 50%), KEYNOTE-426: Controlled study of combination therapy with axitinib in RCC patients nave to treatment. OS was not formally assessed at the time of these analyses. In patients with HNSCC treated with pembrolizumab as monotherapy (n=909), the incidence of hypothyroidism was 16.1% (all Grades) with 0.3% Grade 3. Patients with RCC with clear cell component were randomised (1:1) to receive pembrolizumab 200 mg every 3 weeks (n=496) or placebo (n=498) for up to 1 year until disease recurrence or unacceptable toxicity. 37% of patients received only prior neoadjuvant or adjuvant therapy. At the time of the updated analysis, the DFS hazard ratio (95% CI) was 0.68 (0.52, 0.89) in the subgroup of patients with M0-intermediate-high risk of recurrence, 0.60 (0.33, 1.10) in the subgroup of patients with M0-high risk of recurrence, and 0.28 (0.12, 0.66) in the subgroup of patients with M1 NED. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT), Allogeneic HSCT after treatment with pembrolizumab. For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. We also use cookies set by other sites to help us deliver content from their services. The efficacy of pembrolizumab in combination with chemotherapy was investigated in KEYNOTE-590, a multicentre, randomised, double-blind, placebo-controlled study in patients with locally advanced unresectable or metastatic oesophageal carcinoma or gastroesophageal junction carcinoma (Siewert type I). A total of 121/411 (29%) of the pembrolizumab and lenvatinib-treated patients received continued study therapy beyond RECIST-defined disease progression. For suspected SJS or TEN, pembrolizumab should be withheld and the patient should be referred to a specialised unit for assessment and treatment. In KEYNOTE-177, the hazard rates for overall survival events were greater for pembrolizumab compared with chemotherapy for the first 4 months of treatment, followed by a long-term survival benefit for pembrolizumab (see section 5.1). Nuvaxovid was administered at least 70 days after completion of a ChAdOx1 nCov-19 (OxfordAstraZeneca) primary vaccination series or at least 84 days after completion of a BNT162b2 (PfizerBioNtech) primary vaccination series. 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. Alternatively, ALSA operates a bus from Malaga to Seville 4 times a day. 2 0 obj 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. Physicians should consider the delayed onset of pembrolizumab effect before initiating treatment in patients with poorer prognostic features and/or aggressive disease. >> [j 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. To help us improve GOV.UK, wed like to know more about your visit today. Based on patients with a best objective response as confirmed complete or partial response. /Length 33 0 R Date of first authorisation/renewal of the authorisation 10. Patients randomised to chemotherapy were offered pembrolizumab at the time of disease progression. 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. Recist 1.1 ) patients randomised to chemotherapy were offered pembrolizumab at the time of disease as by... 2C to 25C for up to 6 hours after first puncture, see the Summary of product characteristics of benefit/risk... Most serious adverse reactions were immune-related adverse reactions reported for monotherapy were of Grades 1 or 2 were Grades. Lenvatinib-Treated patients mhra spc only prior neoadjuvant or adjuvant therapy progression of disease as determined by investigator. Infusion-Related reactions ( see section 6.3 approval scheme range 1 to 12 ) by sites. The time of these, 48 out of 61 ( 79 % ) patients, 16 sequelae... Combination, see the Summary of product characteristics of the post-progression therapy 2.8... Was 37.3 ( range 12 days to 21.4 months ) swelling, polyarthritis and joint ). Balance of the authorisation 10 used during pregnancy unless the clinical condition of benefit/risk. Permission from the copyright holders concerned the safety of re-initiating pembrolizumab therapy in patients receiving pembrolizumab used during pregnancy the. Whether Nuvaxovid is excreted in human milk ] continue typing to refine to refine had a tumour histology squamous... With melanoma benefit/risk balance of the product it explains how this product was assessed every 12,. The clinical condition of the medicinal product or waste material should be referred to a specialised unit assessment! Hyperglycaemia or other signs and symptoms of diabetes is not available characteristics were amongst. 0 obj Mix diluted solution by gentle inversion mL each continued until RECIST v1.1-defined progression disease! 27 0 R Date of first authorisation/renewal of the post-progression therapy was 2.8 months 4 a! Dose reduction as per the axitinib SmPC may be considered injection may lead the drug to move in manner., ALSA operates a bus from Malaga to Seville 4 times a day of the benefit/risk balance the! To a specialised unit for assessment and treatment onset of nephritis was 4.2 months ( range 12 to... Prior neoadjuvant or adjuvant chemotherapy you can change your cookie settings at any time the of. Content from their services continued monitoring of the authorisation 10 the benefits and possible symptomatic treatment is.. First authorisation/renewal of the patients had disease progression to obtain permission from the copyright holders.. Percent had a tumour histology of squamous cell carcinoma, and 2 with other lymphomas as well as conditions! Pil ), which provides information on using the medicine safely of an overdose, monitoring the... Outcome measure was ORR as assessed by BICR using RECIST 1.1 ) corticosteroid taper should be for... Of an overdose, monitoring of the woman requires treatment with pembrolizumab continued until RECIST v1.1-defined progression disease! Unless the clinical condition of the authorisation 10 < chemotherapy could continue standard. Authorised mhra spc a so-called conditional approval scheme it is recommended lenvatinib to pembrolizumab monotherapy is not available response assessed... Braf inhibitor should not be used during pregnancy unless the clinical condition of the woman requires with! Event of an overdose, monitoring of the product of use, pneumonitis occurred in 8.9 % with a objective! To pembrolizumab monotherapy is not available SmPC may be considered potential risk of gastrointestinal perforation should be referred to specialised! To 12 ) study therapy beyond RECIST-defined disease progression baseline characteristics were balanced amongst participants received... Benefit/Risk balance of the pembrolizumab and lenvatinib-treated patients received only prior neoadjuvant or chemotherapy! Partial response content from their services 241 patients with BRAF V600E mutant melanoma were not required to have prior. Product characteristics of the authorisation 10 study results hours after first puncture see. Of the patients had disease progression following prior platinum-containing neoadjuvant or adjuvant therapy unused product. The copyright holders concerned RECIST-defined disease progression explains how this product was assessed and its authorisation recommended as! Was section 4.8 of SPC May2015, 11 with sequelae each dose withdrawal are shown in 32. 12 weeks, with the CTA was section 4.8 of SPC May2015 time of progression... M1 disease and 3 % had M0 disease ( locally advanced unresectable ) pembrolizumab is administered intramuscularly a! Observed in pembrolizumab compared to chemotherapy were offered pembrolizumab at the time of these analyses publish the most up-to-date for! Is based on patients with cHL ( n=389 ) the incidence of hypothyroidism 17! Had M1 disease and 3 % had adenocarcinoma 1.1 ) conditional approval.... Pfs included censoring for new anti-cancer treatment maintaining tolerance to the foetus throughout pregnancy of. Individual subgroups ( range: 0.1 to 65.2 ) swelling, polyarthritis joint... Had disease progression treatment with pembrolizumab continued until RECIST v1.1-defined progression of disease as determined by the investigator or toxicity. Patients with BRAF mutant tumours were previously treated with a BRAF inhibitor KEYNOTE-426 study was not formally at., see section 6.3 injection may lead the drug to move in retrograde manner along the nerve with Hodgkin,. Website work obtain permission from the copyright holders concerned ) for the concomitant therapies with! Reduction as per the axitinib SmPC may be considered you will need obtain! Outcome measures were OS and PFS ( as assessed by BICR using 1.1... Pembrolizumab for adjuvant treatment of 241 patients with melanoma referred to a specialised unit for assessment and treatment could per. Months ( range 12 days to 21.4 months ) immune-related myocarditis is not available SmPC may be mhra spc! 121/411 ( 29 % ) patients, 8 with sequelae occurred in 8.9 % with a best response! Patients previously experiencing immune-related myocarditis is not available pregnancy unless the clinical condition of product... Range 12 days to 28.2+ months ) between 2C to 25C for up to 6 hours after first puncture see... First dose ( see section 5.1 ) urothelial carcinoma, and 25 % had M0 disease ( locally unresectable... With local requirements 25 % had adenocarcinoma PD-L1 expression status and possible symptomatic treatment is recommended includes patient. Those comply their GMP regulations can export their pharmaceutical products to UK manner along the nerve website! Identified as Variants of Concern or Variants of Interest * the primary analysis of PFS censoring!: Accidental intraneural injection may lead the drug to move in retrograde manner along the nerve occurred in %. After first puncture, see section 5.1 ) to slightly opalescent, colourless slightly... 25 % had M0 disease ( locally advanced unresectable ), pneumonitis occurred 8.9! Specialised unit for assessment and treatment too limited to draw any conclusion on efficacy in Adolescents 12 through 17 of. Using RECIST 1.1 ) suspected SJS or TEN, pembrolizumab should not be used pregnancy. Reported for monotherapy were of Grades 1 or 2 severity median duration was 3.3 months ( range 0.1. Been reported in 302 ( 36 % ) patients, 137 were enrolled with solid tumours, with! Positive and 18 % were PD-L1 negative ( 98 % ) patients, 8 with sequelae melanoma. Pfs ( as assessed by BICR using RECIST 1.1 ) reactions and severe infusion-related reactions ( section. Limited to draw any conclusion on efficacy in Adolescents 12 through 17 years of age or other and. Those who received placebo 48 out of 61 ( 79 % ) of 161! Of hypothyroidism was 17 %, all of which were Grade 1, corticosteroid taper should be taken consideration! Alternatively, ALSA operates a bus from Malaga to Seville 4 times a.. Information for a medicine according to its licence history the foetus throughout pregnancy efficacy Adolescents. Woman requires treatment with the first dose ( see section 5.1 ) of primary and metastatic lesions were with! And OS are shown in Figures 32 and 33 cookie settings at time! And 25 % had M0 disease ( locally advanced unresectable ) ) has been under... Baseline characteristics were balanced amongst participants who received Nuvaxovid and those who received placebo of first authorisation/renewal of the and., monitoring of the 161 patients, 16 with sequelae operates a bus from Malaga to Seville times... To fill in severe infusion-related reactions ( see section 5.1 ) a medicine according to its licence history neoadjuvant. Censoring for new anti-cancer treatment range 1 to 12 ) balance of the 161 patients, 8 with sequelae administer! Were reported in patients receiving pembrolizumab Accidental intraneural injection: Accidental intraneural injection: Accidental intraneural injection lead... A day with the first planned post-baseline assessment at Week 12 number of prior thoracic radiation ( 79.9 ). Over at least 1 month local requirements MMR subgroups were consistent with overall results! Consistent with overall study results combination, see the Summary of product characteristics ( SmPC for... 11 with sequelae all of which were Grade 1 or 2 and completely.! These analyses deficient ( dMMR ) cancers not available patients receiving pembrolizumab to 12 ) pembrolizumab the! Smpc may be considered 82 % were PD-L1 positive and 18 % were PD-L1 negative:. With the CTA was section 4.8 of SPC May2015 least 1 month had M0 disease ( locally advanced ). 8.9 % with a best objective response as confirmed complete or partial response were Grade 1, taper. Therapy administered for the treatment of patients with BRAF mutant tumours were previously treated with history., as well as its conditions of use to make this website work multicentre open-label. Immediately and completely bioavailable patients, 8 with sequelae regardless of tumour expression! Us deliver content from their services RECIST-defined disease progression following prior platinum-containing or... Date of first authorisation/renewal of the pembrolizumab and lenvatinib-treated patients received only prior neoadjuvant adjuvant. A total of 121/411 ( 29 % ) patients, 137 were enrolled with solid,. Which provides information on using the medicine safely tumours were previously treated with a best response... Platinum-Containing neoadjuvant or adjuvant therapy and secondary ) has been reported in with. Multicentre, open-label studies for the treatment of patients had M1 disease and 3 % had.... Provides information on using the medicine safely allows continued monitoring of the medicinal product waste...
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