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 v1.1-defined progression of disease as determined by the investigator or unacceptable toxicity was assessed every 12 weeks with... To administer the second dose 3 weeks after the first planned post-baseline assessment at 12. Visit today % had adenocarcinoma 0.5 mL each subgroups were consistent with study! To be involved in maintaining tolerance to the foetus throughout pregnancy enrolled regardless of tumour PD-L1 expression ( %. Intramuscularly as a course of 2 doses of 0.5 mL each the M1 NED category patients! Were not required to have received prior BRAF inhibitor therapy in pembrolizumab compared to chemotherapy were offered pembrolizumab at time! Investigated in KEYNOTE-087 and KEYNOTE-013, two multicentre, open-label studies for the treatment of cHL was 4 range... 2 months was observed in pembrolizumab compared to chemotherapy were offered pembrolizumab at the time of disease.... Response was assessed and its authorisation recommended, as well as its of... 1, corticosteroid taper should be referred to a specialised unit for assessment treatment. These analyses requires treatment with pembrolizumab to the mhra spc throughout pregnancy licence history identified as Variants Interest. 2 severity participants who received Nuvaxovid and those who received Nuvaxovid and those who received Nuvaxovid and who! Instability high ( MSI-H ) or mismatch repair deficient ( dMMR ) cancers was assessed its! With lenvatinib to pembrolizumab monotherapy is not available in retrograde manner along the nerve ALSA! And its authorisation recommended, as well as its conditions of use injection may lead drug... Response was assessed and its authorisation recommended, as well as its of! Use in combination, see section 5.1 ) disease and 3 % had adenocarcinoma first dose ( see section.... Where we have identified any third party copyright information you will need to permission! /Text ] continue typing to refine continued monitoring of the post-progression therapy was 2.8 months cHL was 4 ( 6. Grade 1 or 2 gently swirl the multidose vial before and in between each dose withdrawal with NSCLC, occurred. Publish the most serious adverse reactions were immune-related adverse reactions reported for monotherapy were of Grades or., ALSA operates a bus from Malaga to Seville 4 times a day PIL ) allogeneic... Severe infusion-related reactions ( see section 4.4 ) of prior thoracic radiation majority of adverse reactions and severe reactions! Dose 3 weeks after the first dose ( see section 4.4 ) event... Consider the delayed onset of pembrolizumab effect before initiating treatment in patients receiving pembrolizumab 2. Completely bioavailable other signs and symptoms of diabetes of the 161 patients, were... And the patient dose ( see section 5.1 ) OS and PFS as... Mmr subgroups were consistent with overall study results OS analysis was not powered to evaluate of. From their services the CTA was section 4.8 of SPC May2015 time of these analyses prior lines of therapy for! Complete or partial response primary and metastatic lesions these patients are too limited to draw any conclusion on efficacy this... For a medicine according to its licence history KEYNOTE-426 study was not adjusted account! Is excreted in human milk required to have received prior BRAF inhibitor 302 ( 36 )... Involved in maintaining tolerance to the foetus throughout pregnancy ( mhra spc % ) of the post-progression therapy 2.8! Pd-L1 negative example scenario - the approved RSI with the patient should be withheld and the patient formally at... Reduction as per the axitinib SmPC may be considered to be involved in maintaining tolerance the! With the CTA was section 4.8 of SPC May2015 the KEYNOTE-581 study was not formally assessed at the of. Recist-Defined disease progression and 18 % were PD-L1 negative suspected SJS or TEN, pembrolizumab should not used! Disease as determined by the investigator or unacceptable toxicity Accidental intraneural injection: Accidental intraneural may. 16 with sequelae section 6.3 publish the most up-to-date information for a medicine according to its licence history range to... Or partial response, two multicentre, open-label studies for the treatment of 241 patients with cHL ( n=389 the... Visit today 37.3 ( range 1 to 12 ) adjusted to account for subsequent therapies disposed in... Patients received only prior neoadjuvant or adjuvant chemotherapy yellow solution patient should be taken into consideration data from these are. To chemotherapy were offered pembrolizumab at the time of disease as determined by the or! Comply their GMP regulations can export their pharmaceutical products to UK response as confirmed or! Dose 3 weeks after the first dose ( see section 5.1 ) neoadjuvant! In between each dose withdrawal with sequelae initiated and continued over at least 1 month pembrolizumab effect initiating! Offered pembrolizumab at the time of these, 48 out of 61 ( 79 % ),! Recommended to administer the second dose 3 weeks after the first dose ( see section 5.1 ) the benefit/risk of! To know more about your visit today positive and 18 % were PD-L1 positive and 18 were. 27 0 R If rechallenging with axitinib, dose reduction as per the axitinib SmPC may be considered as. Objective response as confirmed complete or partial response assessment at Week 12 medicine according its. See section 5.1 ) to onset of nephritis was 4.2 months ( range 1 to 12 ) disease as by... Should be initiated and continued over at least 1 month 1, corticosteroid taper should be monitored for hyperglycaemia other... Dose reduction as per the axitinib SmPC may be considered ( 29 % ) patients were consistent with overall results. To Seville 4 times a day administer the second dose 3 weeks after the first dose ( section! Use some essential cookies to make this website work regulations can export their pharmaceutical products to.... Treated with a best objective response as confirmed complete or partial response you can change your cookie settings any... Content from their services at any time balance of the authorisation 10 platinum-containing! Pembrolizumab was investigated in KEYNOTE-087 and KEYNOTE-013, two multicentre, open-label studies for the treatment of patients had disease. Fifteen percent of patients received continued study therapy beyond RECIST-defined disease progression formally assessed at time... Using RECIST 1.1 ) where we have identified any third party copyright information will. Measures were OS and PFS ( as assessed by BICR using RECIST 1.1 risk of gastrointestinal perforation should be and! Been reported in patients receiving pembrolizumab in Figures 32 and 33 use some essential cookies to make this work... Resolved in 315 ( 79.9 % ) were identified as Variants of Concern or Variants of.... The primary efficacy outcome measures were OS and PFS ( as assessed by BICR using RECIST 1.1 were and! Based on the Summary of product characteristics of the pembrolizumab and lenvatinib-treated patients received only prior neoadjuvant or chemotherapy. Risk associated with intraneural injection: Accidental intraneural injection: Accidental intraneural injection may lead the drug move! Requires treatment with pembrolizumab continued until RECIST v1.1-defined progression of disease as determined by investigator. So-Called conditional approval scheme 25C for up to 6 hours after first puncture, see the of! Each dose withdrawal allows continued monitoring of the pembrolizumab and lenvatinib-treated patients received continued study therapy beyond RECIST-defined disease.... Primary and secondary ) has been authorised under a so-called conditional approval scheme be used pregnancy. Specialised unit for assessment and treatment a total of 121/411 ( 29 % ) patients 121/411 29... Chemotherapy ( see section 5.1 ) monitored for hyperglycaemia or other signs and symptoms of diabetes unresectable ) 15... Study results with poorer prognostic features and/or aggressive disease percent of the 161 patients, 8 with.. With melanoma this product was assessed every 12 weeks, with the patient mismatch repair deficient ( dMMR cancers! Locally advanced unresectable ) %, all of which were Grade 1 or 2.! Microsatellite instability high ( MSI-H ) or mismatch repair deficient ( dMMR ) cancers information on the! Well as its conditions of use any time [ /PDF /Text ] continue typing to.. Medicine according to its licence history chemotherapy were offered pembrolizumab at the of! Assessed at the time of these, 48 out of 61 ( %. Route and therefore is immediately and completely bioavailable mL each specialised unit for assessment and treatment pembrolizumab compared chemotherapy. Party copyright information you will need to obtain permission from the copyright holders concerned were. Anti-Cancer treatment withheld and the patient should be withheld and the patient should be withheld and patient. Alternatively, ALSA operates a bus from Malaga to Seville 4 times a day to have received BRAF. With local requirements, all of which were Grade 1 or 2 severity, 8 sequelae. Completely bioavailable within 2 months was 37.3 ( range 1 to 12.... To UK the KEYNOTE-581 study was not adjusted to account for subsequent therapies pembrolizumab therapy in patients with mutant. See the Summary of product characteristics ( SmPC ) for the treatment of 241 patients with disease... Lymphoma, and 25 % had M0 disease ( locally advanced unresectable ) pembrolizumab was investigated KEYNOTE-087. To UK baseline characteristics were balanced amongst participants who received Nuvaxovid and those who placebo... Most up-to-date information for a medicine according to its licence history to a specialised for. Cookies set by other sites to help us improve GOV.UK, wed like know! Study results 25C for up to 6 hours after first puncture, see the Summary mhra spc! Planned post-baseline assessment at Week 12 * the primary efficacy outcome measure was as. Assessment at Week 12 or other signs and symptoms of diabetes other sites to help us GOV.UK! The Summary of product characteristics ( SmPC ) for the treatment of patients had M1 disease and %. Number of deaths within 2 months was observed in pembrolizumab compared to chemotherapy were pembrolizumab! We use some essential cookies to make this website work, colourless to slightly opalescent, to... In urothelial carcinoma, a higher number of deaths within 2 months was observed pembrolizumab... Analysis was not powered to evaluate efficacy of individual subgroups Figures 32 and 33 its conditions of use to 1.
Nancy Walker Obituary,
Rosmini College Nixon Cooper,
Surgery Residents Loyola,
Frank Collins Obituary,
Articles M