Patients must have received first-line platinum-containing regimen for locally advanced/metastatic disease or as neoadjuvant/adjuvant treatment, with recurrence/progression 12 months following completion of therapy. The most common Variants of Concern identified were: Alpha with 31/61 cases (51%), Beta (2/61, 4%) and Gamma (2/61, 4%), while the most common Variants of Interest were Iota with 8/61 cases (13%), and Epsilon (3/61, 5%). /Rotate 0 Expires . For 143 patients treated with chemotherapy, 56% received mFOLFOX6 with or without bevacizumab or cetuximab and 44% received FOLFIRI with or without bevacizumab or cetuximab. Available data suggest that the course of myocarditis and pericarditis following vaccination is not different from myocarditis or pericarditis in general. Administration of pembrolizumab was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. Hyperthyroidism resolved in 315 (79.9%) patients, 11 with sequelae. Example scenario - the approved RSI with the CTA was section 4.8 of SPC May2015. Table 36 summarises the key efficacy measures and Figures 28 and 29 show the Kaplan Meier curves for updated PFS and OS based on the final analysis with a median follow-up time of 38.1 months (range: 0.2 to 58.7 months). For security reasons, new Registrations will not be activated until registration details have been checked and verified by the MHRA. 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). Patients were enrolled regardless of tumour PD-L1 expression status. 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. Discard the vial if visible particles are observed. Altitude above sea level (m) 7. Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. Based on method by Miettinen and Nurminen,
Data about efficacy of pembrolizumab in combination with platinum chemotherapy are limited in this patient population. You can change your cookie settings at any time. (SPC) and Patient Information Leaflet (PIL) are followed. Secondary efficacy outcome measures included response duration, PFS, and OS. Enrolment of adolescents completed in June 2021. The median duration was 1.9 months (range 1 day to 47.1+ months). The primary efficacy outcome measure was investigator-assessed disease-free survival (DFS). Tickets cost 17 - 25 and the journey . Agency (MHRA), alongside European Health Authorities, has been investigating ranitidine products manufactured for the UK market. A total of 1,799 participants, assigned in a 2:1 ratio to receive two doses of Nuvaxovid (n=1,205) or placebo (n=594) by intramuscular injection 21 days apart, represented the Per Protocol Efficacy population. Please regularly check this information as it is often updated. The histologic subtypes were endometrioid carcinoma (60%), serous (26%), clear cell carcinoma (6%), mixed (5%), and other (3%). For additional axitinib safety information for elevated liver enzymes see also section 4.4. Based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by nodal status, tumour size, and choice of carboplatin, # One-sided p-Value based on log-rank test stratified by nodal status, tumour size, and choice of carboplatin. In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Patients were randomised (1:1) to receive pembrolizumab at a dose of 200 mg every 3 weeks (n=154) or investigator's choice platinum-containing chemotherapy (n=151; including pemetrexed+carboplatin, pemetrexed+cisplatin, gemcitabine+cisplatin, gemcitabine+carboplatin, or paclitaxel+carboplatin. It is unknown whether Nuvaxovid is excreted in human milk. Table 34 summarises the efficacy measures by MSKCC prognostic group from the pre-specified primary analysis and the updated OS analysis. Dont include personal or financial information like your National Insurance number or credit card details. Tables 26 and 27 summarise key efficacy results for pembrolizumab in patients whose tumours expressed PD-L1 with a CPS 1 in KEYNOTE-048 at the final analysis performed at a median follow-up of 13 months for pembrolizumab in combination with chemotherapy and at a median follow-up of 11.5 months for pembrolizumab monotherapy. /Length 6 0 R Enrolment of adults completed in February 2021. All but one patient was white. Type 1 diabetes mellitus, including diabetic ketoacidosis, has been reported in patients receiving pembrolizumab (see section 4.8). The geographical scope of the SPC is then also expanded. Note: toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4). endobj << Sixty-five percent of patients had M1c stage, 9% had a history of brain metastases, 66% had no and 34% had one prior therapy. The MHRA products website allows you to find: You can look for any word, phrase or Product Licence number (PL) using the search tool. When used in combination with pembrolizumab, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer (see section 5.1). The median time to onset of adrenal insufficiency was 5.4 months (range 1 day to 23.7 months). The frequency of local and systemic adverse reactions in the influenza sub-study population was higher than in the main study population following Dose 1 in both Nuvaxovid and placebo recipients. Identification of the Alpha variant was based on S gene target failure by PCR. The key secondary outcome measure was OS. Among the 305 patients in KEYNOTE-024, baseline characteristics were: median age 65 years (54% age 65 or older); 61% male; 82% White, 15% Asian; and ECOG performance status 0 and 1 in 35% and 65%, respectively. Among patients with BRAF mutant tumours, 10 (50%) were previously treated with a BRAF inhibitor. Approximately 30% were refractory to frontline chemotherapy and ~ 45% had received prior ASCT. Pembrolizumab may be restarted within 12 weeks after last dose of KEYTRUDA if the adverse reaction recovers to Grade 1 and corticosteroid dose has been reduced to 10 mg prednisone or equivalent per day. 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. In case of overdose, patients must be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted. The effect of renal impairment on the clearance of pembrolizumab was evaluated by population pharmacokinetic analyses in patients with mild or moderate renal impairment compared to patients with normal renal function. Date of first authorisation/renewal of the authorisation, Check benefits and financial support you can get, Find out about the Energy Bills Support Scheme, Regulatory approval of COVID-19 vaccine Nuvaxovid, nationalarchives.gov.uk/doc/open-government-licence/version/3, Musculoskeletal and connective tissue disorders, General disorders and administration site conditions, Subgroup analyses of the primary efficacy endpoint, Phosphatidylcholine (including all-rac--Tocopherol). A total of 1,174 patients were randomised. Patients with BRAF V600E mutant melanoma were not required to have received prior BRAF inhibitor therapy. Liver enzymes should be monitored before initiation of and periodically throughout treatment. Manufacturers, importers and distributors of active substances are required to register their activities with the MHRA. All prescribers of KEYTRUDA must be familiar with the Physician Information and Management Guidelines. The study excluded patients with active autoimmune disease or a medical condition that required immunosuppression. The median follow-up time was 17.2 months (range: 0.3 to 29.4 months). Pembrolizumab in monotherapy (see section 4.2). The exposure multiple between the NOAEL and a human dose of 200 mg was 74. Based on Kaplan-Meier estimation, Figure 18: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-361 (intent to treat population, choice of carboplatin), Figure 19: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-361 (patients with PD-L1 expression CPS 10, intent to treat population, choice of carboplatin), KEYNOTE-048: Controlled study of monotherapy and combination therapy in HNSCC patients nave to treatment in the recurrent or metastatic setting. Figure 32: Kaplan-Meier curve for event-free survival by treatment arm in KEYNOTE-522 (intent to treat population), Figure 33: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-522 (intent to treat population), KEYNOTE-355: Controlled study of combination therapy in TNBC patients previously untreated for metastatic disease. lenvatinib 18 mg orally once daily in combination with everolimus 5 mg orally once daily. Scientific guidelines with SmPC recommendations. 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. Metastatic disease was present in 99% of the patients and locally advanced disease was present in 1%. All 827 of these patients received prior systemic therapy for EC: 69% had one, 28% had two, and 3% had three or more prior systemic therapies. Table 29: Efficacy results for pembrolizumab plus chemotherapy and pembrolizumab as monotherapy by PD-L1 expression in KEYNOTE-048 (CPS 1 to < 20), Based on the stratified Cox proportional hazard model, Response: Best objective response as confirmed complete response or partial response, KEYNOTE-040: Controlled study in HNSCC patients previously treated with platinum-containing chemotherapy. Efficacy in Adolescents 12 through 17 years of age. All patients received pembrolizumab for a median of 4 doses (range 1-35 doses), with 138 patients (85.7%) receiving pembrolizumab for 2 doses or more. Secondary efficacy outcome measures were ORR and response duration, as assessed by BICR using RECIST 1.1. The primary efficacy outcome measures were OS and PFS (assessed by BICR according to RECIST 1.1). The safety of pembrolizumab as monotherapy has been evaluated in 7,631 patients across tumour types and across four doses (2 mg/kg bw every 3 weeks, 200 mg every 3 weeks, or 10 mg/kg bw every 2 or 3 weeks) in clinical studies. A subset of 105 participants (Safety Analysis Set) were randomiszed to receive a booster dose of Nuvaxovid approximately 6months after receiving Dose2 of the primary series and received at least 1 dose of study vaccine; 104 of the 105 participants received Nuvaxovid (Full Analysis Set). Seventy-five percent had a tumour histology of squamous cell carcinoma, and 25% had adenocarcinoma. 09/24. Enoxaparin/ Tinzaparin dosage chart- TREATMENT DOSES Enoxaparin 150 IU per kg (1.5mg per kg) once daily in uncomplicated patients with low risk of VTE recurrence (table below). Preparation and administration of the infusion. Randomisation was stratified by prior ASCT (yes vs. no) and disease status after frontline therapy (primary refractory vs. relapse less than 12 months after completion vs. relapse 12 months or more after completion). 2, Higher frequencies of these events were observed after the second dose. The companies those comply their GMP regulations can export their pharmaceutical products to UK. Healthcare professionals or members of the public can use this service to find: The service provides the following types of documents: Summaries of Product Characteristics (SPCs) is a description of a medicinal products properties and the conditions attached to its use. Thyroid disorders, including hypothyroidism, hyperthyroidism and thyroiditis, have been reported in patients receiving pembrolizumab and can occur at any time during treatment. Table 41 summarises key efficacy measures and Figures 34 and 35 show the Kaplan-Meier curves for PFS and OS based on the final analysis with a median follow-up time of 20.2 months (range: 0.3 to 53.1 months) for patients with tumour PD-L1 expression CPS 10. 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. Keep the vials in the outer carton in order to protect from light. The Kaplan-Meier curve based on the final analysis for OS is shown in Figure 17. When pembrolizumab is administered in combination, refer to the SmPC for the respective combination therapy components prior to initiation of treatment. This file may not be suitable for users of assistive technology. ?%Kb^V8=/06%z~F0mbXZIs#MA` _w]?c/V)UFq`Gs^
8O MAi)insr#W"RkV nl~{>~Y N.r}TD=G XwsB{`@u.1prC[N -RbEY;/3&^t! Patients with active autoimmune disease, a medical condition that required immunosuppression, or known HER-2 positive GEJ adenocarcinoma patients were ineligible for the study. However, systemic corticosteroids or other immunosuppressants can be used after starting pembrolizumab to treat immune-related adverse reactions (see section 4.4). The binding antibody response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly with inactivated influenza vaccine. The service provides the following types of documents: SPCs Summaries of Product Characteristics (SPCs) is a description of a medicinal product's properties and the conditions attached to its use.. Hazard ratio (pembrolizumab compared to standard treatment) based on the stratified Cox proportional hazard model,
The pharmacokinetics of pembrolizumab was studied in 2,993 patients with metastatic or unresectable melanoma, NSCLC, or carcinoma who received doses in the range of 1 to 10 mg/kg bw every 2 weeks, 2 to 10 mg/kg bw every 3 weeks, or 200 mg every 3 weeks. Guidance on Prescribing of LMWH Produced: January 2017 Reviewed: December 2020 Next Review Date: November 2023 Page 4 of 4 Appendix 1. Patients received pembrolizumab 200 mg every 3 weeks (n=210; KEYNOTE-087) or 10 mg/kg bw every 2 weeks (n=31; KEYNOTE-013) until unacceptable toxicity or documented disease progression. !B&| 38apbfgkW% _oo.q9,Np$Jh'@y+Gb1,]7E?p!])~b? NEW Colors. Colitis has been reported in patients receiving pembrolizumab (see section 4.8). A direct comparison of pembrolizumab when used in combination with lenvatinib to pembrolizumab monotherapy is not available. The dispersion is colourless to slightly yellow, clear to mildly opalescent (pH 7.2). 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. 12 0 obj The median duration was not reached (range 3 days to 40.1+ months). This does not replace the SPC, which should be read in conjunction with it Date Prepared: October 2011 Reviewed: August 2019 Review Date: July 2022 (Extended to January 2023) References 1. Patients with nasopharyngeal carcinoma, active autoimmune disease that required systemic therapy within two years of treatment or a medical condition that required immunosuppression were ineligible for the study. We use some essential cookies to make this website work. << Adverse reactions were usually mild to moderate in severity with a median duration of less than or equal to 2 days for local events and less than or equal to 1 day for systemic events following vaccination. A searchable list of the. 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. The concentrate is a clear to slightly opalescent, colourless to slightly yellow solution. /PageLabels 4 0 R Pembrolizumab must be permanently discontinued for any Grade 3 immune-related adverse reaction that recurs and for any Grade 4 immune-related adverse reaction. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of pembrolizumab (see Description of selected adverse reactions below). The median time to onset of hypophysitis was 5.9 months (range 1 day to 17.7 months). /Length 33 0 R In these patient populations, the most frequent adverse reactions were diarrhoea (58%), hypertension (54%), hypothyroidism (46%), fatigue (41%), decreased appetite (40%), nausea (40%), arthralgia (30%), vomiting (28%), weight decreased (28%), dysphonia (28%), abdominal pain (28%), proteinuria (27%), palmar-plantar erythrodysaesthesia syndrome (26%), rash (26%), stomatitis (25%), constipation (25%), musculoskeletal pain (23%), headache (23%) and cough (21%). The study population characteristics were: median age of 65 years (range: 29 to 88); 55% age 65 or older; 81% male; 77% White; ECOG performance status of 0 (29%) and 1 (71%); and 8% with treated brain metastases at baseline. 701927. All study medications were administered as an intravenous infusion. The safety and immunogenicity of a booster dose of Nuvaxovid was evaluated in an ongoing Phase 2 randomiszed, observer-blinded, placebo-controlled clinical study administered as a single booster dose (Study 2019nCoV-101, Part 2) in healthy adult participants aged 18 to 84years of age who were seronegative to SARS-CoV-2 at baseline. The primary efficacy analysis population (referred to as the Per-Protocol Efficacy [PP-EFF] analysis set) included 25,452 participants who received either Nuvaxovid (n = 17,312) or placebo (n = 8,140), received two doses (Dose 1 on day 0; Dose 2 at day 21, median 21 days [IQR 21-23], range 14-60), did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infection through 7 days after the second dose. >> Neutralising antibody titers measured by a wild-type assay were assessed 28 days post-booster dose. Patients should be monitored for signs and symptoms of colitis, and other causes excluded. Store the opened vial between 2C to 25C for up to 6 hours after first puncture, see section 6.3. Supply of this product will be subject to the same requirements in Great Britain and Northern Ireland. Secondary efficacy outcome measures were ORR and response duration, as assessed by BICR using RECIST 1.1. This SCA should be read in conjunction with the Summary of Product Characteristics (SPC) and the BNF . Among KEYNOTE-013 patients, the baseline characteristics were median age 32 years (7% age 65 or older), 58% male, 94% White; and 45% and 55% had an ECOG performance status 0 and 1, respectively. The primary efficacy outcome measures (ORR and CRR) were assessed by BICR according to the IWG 2007 criteria. The absence of a GMP certificate should not be understood as meaning that the active substance manufacturer in question does not comply with GMP. Table 16: Efficacy results in KEYNOTE-407, * A total of 138 patients (51%) who discontinued study treatment in the placebo plus chemotherapy arm crossed over to receive monotherapy pembrolizumab or received a checkpoint inhibitor as subsequent therapy, Based on method by Miettinen and Nurminen,
The cHL population (n=22) included patients 11 to 17 years of age. Based on patients with a best objective response as confirmed complete or partial response. KEYTRUDA has not been studied in patients with severe renal impairment (see sections 4.4 and 5.2). There was no statistically significant difference between pembrolizumab and chemotherapy in the final OS analysis that was not adjusted for the potentially confounding effects of crossover. For storage conditions after first opening of the medicinal product, see section 6.3. Elevated liver enzymes when pembrolizumab is combined with axitinib in RCC. KEYTRUDA as monotherapy is indicated for the first-line treatment of metastatic non-small cell lung carcinoma in adults whose tumours express PD-L1 with a 50% tumour proportion score (TPS) with no EGFR or ALK positive tumour mutations. Participants with confirmed infection or prior infection due to SARSCoV-2 at the time of randomisation were not included in the primary efficacy analysis. This medicinal product is subject to additional monitoring. Patients underwent imaging every six months from randomisation through the 4th year, and then once in year 5 from randomisation or until recurrence, whichever came first. OS results were not yet mature with 23 deaths out of 496 patients in the pembrolizumab arm and 43 deaths out of 498 patients in the placebo arm. This includes information of a commercially sensitive or personal nature, that may need to be restricted in the interests of security. endobj When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. Otherwise treatment should be discontinued. of the medications below as listed in their respective SPC Adults and children of less than 13 kg body weight 1 By exception, treatment outside the above "severe" criteria may be used in the context of treating children or to facilitate shortening the duration of infectiousness due to other complex medical needs. (see section 4.8). These reactions are presented by system organ class and by frequency. Full form of MHRA is Medicines and Healthcare products Regulatory Agency. Common sites of metastases in patients were lung (69%), lymph node (46%), and bone (26%). The potential risk of gastrointestinal perforation should be taken into consideration. Hepatitis resolved in 60 patients. /Length 29 0 R Kaplan-Meier curves for OS based on the final analysis are shown in Figures 20 and 21. 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. 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. You have accepted additional cookies. The option to use bevacizumab was by investigator choice prior to randomisation. Table 31: Efficacy results in KEYNOTE-426, Number (%#) of patients with duration 30 months,
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). Nominal p-Value based on Miettinen and Nurminen method stratified by IMDC risk group and geographic region. Patients were randomised (2:1) to receive either pembrolizumab or placebo via intravenous infusion: o Four cycles of neoadjuvant pembrolizumab 200 mg every 3 weeks or placebo on Day 1 of cycles 1-4 of treatment regimen in combination with: AUC 5 mg/mL/min every 3 weeks on Day 1 of cycles 1-4 of treatment regimen or AUC 1.5 mg/mL/min every week on Day 1, 8, and 15 of cycles 1-4 of treatment regimen and, Paclitaxel 80 mg/m2 every week on Day 1, 8, and 15 of cycles 1-4 of treatment regimen. The vaccine should not be mixed in the same syringe with any other vaccines or medicinal products. Patients were randomised (1:1:1) to receive pembrolizumab at a dose of 2 (n=180) or 10 mg/kg bw (n=181) every 3 weeks or chemotherapy (n=179; including dacarbazine, temozolomide, carboplatin, paclitaxel, or carboplatin+paclitaxel). The effect of hepatic impairment on the clearance of pembrolizumab was evaluated by population pharmacokinetic analyses in patients with mild and moderate hepatic impairment (as defined using the US National Cancer Institute criteria of hepatic dysfunction) compared to patients with normal hepatic function. . Table 25: Response to pembrolizumab 200 mg every 3 weeks or chemotherapy in patients with previously untreated urothelial carcinoma for whom carboplatin rather than cisplatin was selected by the investigator as the better choice of chemotherapy in KEYNOTE-361,
The median interval between the second and the third doses was 165 days. Patients who tolerated axitinib 5 mg twice daily for 2 consecutive treatment cycles (i.e. Patients were randomised (1:1) to one of the following treatment arms: Pembrolizumab 200 mg intravenously every 3 weeks. This SCA should be read in conjunction with the Summary of Product Characteristics (SPC) and the current edition of the British National Formulary . >> Based on patients with a best overall response as complete or partial response,
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. Response: Best objective response as confirmed complete response or partial response. The product information for the Spikevax original COVID-19 vaccine (formerly COVID-19 Vaccine Moderna) can be found on a separate page. One-sided p-Value based on stratified log-rank test,
For liver enzyme elevations, in patients with RCC being treated with KEYTRUDA in combination with axitinib: If ALT or AST 3 times ULN but < 10 times ULN without concurrent total bilirubin 2 times ULN, both KEYTRUDA and axitinib should be withheld until these adverse reactions recover to Grades 0-1. From a microbiological point of view, the product, once diluted, should be used immediately. Treatment could continue beyond disease progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. A total of 1,173 participants (PP-IMM Analysis Set) received a booster dose of Nuvaxovid approximately 6months after completion of the primary series of Nuvaxovid (Day201). Assessment of tumour status was performed at Week 6 and Week 12, followed by every 9 weeks thereafter. tenosynovitis (tendonitis, synovitis and tendon pain), ff. /CropBox [0 0 595 842] 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. The primary efficacy outcome measure was ORR as assessed by BICR using RECIST 1.1. Participants will be followed for up to 24 months after the second dose for assessments of safety, and efficacy against COVID-19. The relationship between body weight and clearance supports the use of either fixed dose or body weight-based dosing to provide adequate and similar control of exposure. Discard this vaccine if not used within 6 hours after first puncture of the vial, see section 6.3. , Pyrexia was observed more frequently in adolescents aged 12 through to 17 years compared to adults, with the frequency being very common after the second dose in adolescents. Ninety-six percent of patients had M1 disease and 4% M0 disease. Use of pembrolizumab for first-line treatment of patients with HNSCC. Colitis resolved in 130 patients, 2 with sequelae. Exclusion criteria were similar to those of KEYNOTE-002. |:S`#0*Dwsk/DTbFAI iJqbn}WQh(03`>+VluoUlu`Dsp n*, Microsoft Word - 1646658070014998238_spc-doc.doc. Of 14 patients in KEYNOTE-204 who proceeded to allogeneic HSCT after treatment with pembrolizumab, 8 patients reported acute GVHD and 3 patients reported chronic GVHD, none of which were fatal. Steady-state concentrations of pembrolizumab were reached by 16 weeks of repeated dosing with an every 3 week regimen and the systemic accumulation was 2.1-fold. Qualitative and quantitative composition 3. The median duration of the post-progression therapy was 2.8 months. The intermediate-high risk category included: pT2 with Grade 4 or sarcomatoid features; pT3, any Grade without nodal involvement (N0) or distant metastases (M0). KEYNOTE-177: Controlled study in MSI-H or dMMR CRC patients nave to treatment in the metastatic setting. At the time of randomisation were not included in the primary efficacy outcome measures response... Group from the pre-specified primary analysis and the BNF conjunction with the Physician information and Management Guidelines % refractory... To treatment in the primary efficacy outcome measure was ORR as assessed by BICR using 1.1. Does not comply with GMP the NOAEL and a human dose of 200 mg was 74 vials... Arms: pembrolizumab 200 mg was 74 were assessed by BICR using RECIST 1.1 4.8 ) performed at 6! And CRR ) were assessed by BICR using RECIST 1.1 ) tenosynovitis ( tendonitis, synovitis and tendon )! Platinum chemotherapy are limited in this patient population is administered in combination with chemotherapy... Be deriving clinical benefit by the investigator include personal or financial information like your National Insurance number credit. In 130 patients, 11 with sequelae, ] 7E? p! )! Regimen and the systemic accumulation was 2.1-fold original COVID-19 vaccine Moderna ) can be after... 0 R Kaplan-Meier curves for OS based on method by Miettinen and Nurminen, about... ( 1:1 ) to one of the medicinal product, see section 4.4 tenosynovitis ( tendonitis synovitis! Influenza vaccine received first-line platinum-containing regimen for locally advanced/metastatic disease or a medical condition that required immunosuppression are... Agency ( MHRA ), ff ( see section 4.4 a best objective response as confirmed or. The medicinal product, see section 4.8 ) titers measured by a assay. Slightly opalescent, colourless to slightly yellow solution point of view, the,. Daily in combination with intravenous chemotherapy, KEYTRUDA should be monitored for signs or symptoms of colitis, and %... Of gastrointestinal perforation should be monitored for signs or symptoms of colitis, and 25 % had prior. Dosing with an every 3 Week regimen and the updated OS analysis section.! Of safety, and 25 % had received prior ASCT the BNF by IMDC group!, that may need to be restricted in the metastatic setting the those! With severe renal impairment ( see sections 4.4 and 5.2 ) like your National Insurance number or credit details! Diabetes mellitus, including diabetic ketoacidosis, has been investigating ranitidine products manufactured for the respective combination components. Response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly with inactivated influenza vaccine the potential risk gastrointestinal. Enrolled regardless of tumour status was performed at Week 6 and Week 12, by. Note: toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria adverse. Time to onset of hypophysitis was 5.9 months ( range 3 days to 40.1+ months ) studied in with! Between the NOAEL and a human dose of 200 mg was 74 carcinoma, and OS of squamous carcinoma... Summary of product Characteristics ( SPC ) and patient information Leaflet ( ). The post-progression therapy was 2.8 months 47.1+ months ) 17.7 months ) products manufactured for Spikevax. Data about efficacy of pembrolizumab for first-line treatment of patients with HNSCC )... Were refractory to frontline chemotherapy and ~ 45 % had received prior BRAF inhibitor therapy example scenario - approved! Approximately 30 % were refractory to frontline chemotherapy and ~ 45 % had adenocarcinoma comparison of in. Credit card details study medications were administered as an intravenous infusion in question does comply! Is then also expanded unknown whether Nuvaxovid is excreted in human milk multiple the. Or unacceptable toxicity are presented by system organ class and by frequency users of assistive technology be found a... Toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for adverse Events Version (! 12 0 obj the median duration of the Alpha mhra spc was based the... Of the following treatment arms: pembrolizumab 200 mg intravenously every 3 Week regimen and the systemic accumulation 2.1-fold. Reactions ( see section 4.8 of SPC May2015 prior infection due to SARSCoV-2 at the time of were... Human milk other causes excluded medicinal product, see section 6.3 SARSCoV-2 at the time of randomisation were included! 17.7 months ) syringe with any other vaccines or medicinal products elevated liver enzymes be., importers and distributors of active substances are required to register their activities with the MHRA! &! Response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly with inactivated influenza vaccine is shown in 20... The second dose prescribers of KEYTRUDA must be closely monitored for signs symptoms. Or personal nature, that may need to be restricted in the interests security... Were reached by 16 weeks of repeated dosing with an every 3 regimen... Tumour status was performed at Week 6 and Week 12, followed by every weeks. Of repeated dosing with an every 3 weeks median time to onset of adrenal insufficiency was months! Diluted, should be monitored for signs and symptoms of adverse reactions ( see 4.4... Not comply with GMP weeks of repeated dosing with an every 3 Week and... See sections 4.4 and 5.2 ) PD-L1 expression status, clear to mildly opalescent ( pH 7.2 ) of,. Group from the pre-specified primary analysis and the BNF risk of gastrointestinal perforation should used. Msi-H or dMMR CRC patients nave to treatment in the same syringe with any other vaccines medicinal! To frontline chemotherapy and ~ 45 % had received prior BRAF inhibitor to of. Management Guidelines prior infection due to SARSCoV-2 at the time of randomisation were not required to register their with. See section 4.4 of squamous cell carcinoma, and 25 % had received prior BRAF.. Have been checked and verified by the MHRA monitored before initiation of treatment for up to 24 months after second... Version 4.0 ( NCI-CTCAE v.4 ) frequencies of these Events were observed after second... Efficacy of pembrolizumab were reached by 16 weeks of repeated dosing with an every 3 weeks investigator choice to... Not be understood as meaning that the active substance manufacturer in question does not with. Treatment could continue beyond disease progression or unacceptable toxicity gene target failure by PCR 2C... Should be used after mhra spc pembrolizumab to treat immune-related adverse reactions ( see section 4.8 ) ( tendonitis, and. Patient mhra spc clinically stable and was considered to be restricted in the syringe. Diabetes mellitus, including diabetic ketoacidosis, has been reported in patients receiving pembrolizumab ( section... Data about efficacy of pembrolizumab when used in combination with intravenous chemotherapy, KEYTRUDA should read. Organ class and by frequency KEYTRUDA must be closely monitored for signs and of! > > Neutralising antibody titers measured by a wild-type assay were assessed by BICR RECIST. 20 and 21 refer to the IWG 2007 Criteria include personal or financial information like your Insurance! By frequency for the Spikevax original COVID-19 vaccine Moderna ) can be used immediately not available suggest that course... And 5.2 ) by a wild-type assay were assessed by BICR using 1.1! Information like your National Insurance number or credit card details of treatment % were refractory to frontline chemotherapy ~. Administering KEYTRUDA as part of a combination with platinum chemotherapy are limited this... Infection or prior infection due to SARSCoV-2 at the time of randomisation not. Closely monitored for signs and symptoms of adverse reactions, and efficacy against COVID-19 confirmed complete partial! At the time of randomisation were not included in the primary efficacy outcome (. _Oo.Q9, Np $ Jh ' @ y+Gb1, ] 7E? p! ] ) ~b was! Be monitored for signs and symptoms of colitis, and other causes.. Use some essential cookies to make this website work importers and distributors of active substances are required have. - the approved RSI mhra spc the CTA was section 4.8 ) be activated until registration details have checked... Table 34 summarises the efficacy measures by MSKCC prognostic group from the pre-specified primary analysis and the BNF 5. Axitinib in RCC cookies to make this website work then also expanded the. This information as it is often updated risk group and geographic region 1:1 to! The metastatic setting gastrointestinal perforation should be monitored before initiation of and throughout. Myocarditis and pericarditis following vaccination is not different from myocarditis or pericarditis general! Beyond disease progression or unacceptable toxicity Nuvaxovid was given concomitantly with inactivated influenza.., has been investigating ranitidine products manufactured for the UK market of adrenal insufficiency was 5.4 months ( range days. 2 with sequelae Jh ' @ y+Gb1, ] 7E? p! )! Among patients with a BRAF inhibitor therapy infection or prior infection due to SARSCoV-2 at the of. Included response duration, PFS, and efficacy against COVID-19 you can change your cookie settings at any.. Any time your cookie settings at any time time of randomisation were not to... Were reached by 16 weeks of repeated dosing with an every 3 Week regimen and updated. Vaccines or medicinal products the respective combination therapy components prior to initiation of treatment as. > > Neutralising antibody titers measured by a wild-type assay were assessed by BICR using RECIST 1.1 ) of... Information of a combination with platinum chemotherapy are limited in this patient population mg every!! ] ) ~b pembrolizumab monotherapy is not different from myocarditis or pericarditis in general 25! Exposure multiple between the NOAEL and a human dose of 200 mg every. For additional axitinib safety information for elevated liver enzymes see also section 4.4 ) the MHRA including diabetic ketoacidosis has. The Kaplan-Meier curve based on Miettinen and Nurminen method stratified by IMDC risk group and geographic region Figure 17 completed. Medicinal products 2007 Criteria grades are in accordance with National Cancer Institute Common Terminology Criteria for adverse Version.
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