PD-L1 expression was tested retrospectively by immunohistochemistry (IHC) assay with the 22C3 anti-PD-L1 antibody. In the PP-EFF analysis set for participants who received Nuvaxovid, median age was 28 years (range: 18 to 84 years); 40% were female; 91% were Black/African American; 2% were White; 3% were multiple races, 1% were Asian; and 2% were Hispanic or Latino; and 5.5% were HIV-positive. It explains how to use and prescribe a medicine. In order to avoid intraneural injection and to prevent nerve injuries in connection with Eighty-four percent were refractory to at least one prior therapy, including 35% who were refractory to first line therapy. There are no notable differences in median Cmax between cHL and other tumour types. The key eligibility criteria for this study were metastatic squamous NSCLC, regardless of tumour PD-L1 expression status, and no prior systemic treatment for metastatic disease. The safety and efficacy of pembrolizumab were also investigated in KEYNOTE-042, a multicentre, controlled study for the treatment of previously untreated locally advanced or metastatic NSCLC. Chemical and physical in-use stability has been demonstrated for 6 hours at 2C to 25C from the time of first needle puncture to administration. Efficacy results in this subpopulation were consistent with the ITT population. It explains how to use and prescribe a medicine. This medicinal product is subject to additional monitoring. The primary OS analysis was not adjusted to account for subsequent therapies. Nominal p-Value based on log-rank test stratified by American Joint Committee on Cancer (AJCC) 8th edition T stage. Patients without disease progression could be treated for up to 24 months. Efficacy results by MSKCC prognostic group are summarised in Table 34. Assessment of tumour status was performed every 8 weeks. Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo. A total of 861 patients were randomised. 15 0 obj To confirm the patient has no contra-indications to treatment and consider the relevance of any cautions. 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. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT), Allogeneic HSCT after treatment with pembrolizumab. 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). The presence of a minor infection and/or low-grade fever should not delay vaccination. Patients were treated with pembrolizumab until unacceptable toxicity or disease progression. Based on method by Miettinen and Nurminen, Assessment of tumour status was performed at Week 9 and then every 9 weeks for the first year, followed by every 12 weeks thereafter. /CropBox [0 0 595 842] The management guidelines for these adverse reactions are described in section 4.4. 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). << Patients with Grades 1 or 2 infusion reaction may continue to receive pembrolizumab with close monitoring; premedication with antipyretic and antihistamine may be considered. Forty-five percent had no prior therapies for advanced melanoma. Secondary efficacy outcome measures were ORR and duration of response, according to RECIST v1.1, as assessed by investigator. Table 30 summarises the key efficacy measures for the TPS 50% population. << This medicinal product contains 106 mg (5.1mmol) sodium per 10 ml dose, equivalent to 5.3% of the WHO recommended maximum daily intake for sodium. Microsoft Word - 1646658070014998238_spc-doc.doc Marketing authorisation holder 8. Working together across Sussex. Table 42: Efficacy results in KEYNOTE-775, Clear to slightly opalescent, colourless to slightly yellow solution, pH 5.2 5.8. The median duration of the post-progression therapy was 2.8 months. Dont include personal or financial information like your National Insurance number or credit card details. The safety and efficacy of pembrolizumab were evaluated in KEYNOTE-045, a multicentre, open-label, randomised (1:1), controlled study for the treatment of locally advanced or metastatic urothelial carcinoma in patients with disease progression on or after platinum-containing chemotherapy. The intermediate-high risk category included: pT2 with Grade 4 or sarcomatoid features; pT3, any Grade without nodal involvement (N0) or distant metastases (M0). Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. This publication is available at https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-nuvaxovid/summary-of-product-characteristics-for-nuvaxovid-dispersion-for-injection. Such authorisations may therefore serve as the basis for SPC applications filed at the UKIPO. [j KEYTRUDA is a humanised monoclonal antibody which binds to the programmed cell death-1 (PD-1) receptor and blocks its interaction with ligands PD-L1 and PD-L2. Patients who received prior therapy for melanoma other than surgery were ineligible. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Of the 540 patients, 61% were male, 43% were 65 years (median age was 62 years [range 15-89]) and 98% were white. /Resources 24 0 R Administration of pembrolizumab was permitted beyond RECIST-defined disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator. Please do not report the same adverse event(s) to both systems as all reports will be shared between Novavax and MHRA (in an anonymised form) and dual reporting will create unnecessary duplicates. 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. Long-term safety data of pembrolizumab in adolescents with Stage IIB, IIC and III melanoma treated in the adjuvant setting are currently unavailable. An exploratory subgroup analysis was performed in KEYNOTE-048 in patients whose tumours expressed PD-L1 CPS 1 to < 20 [pembrolizumab plus chemotherapy: n=116 (45%) vs. standard treatment: n=125 (49%) and pembrolizumab monotherapy: n=124 (48%) vs. standard treatment: n=133 (52%)] (see Table 29). 6.5 Nature and contents of container PVC/Aluminium thermoformed blister of 10 soft capsules. When reporting, please include the vaccine brand and batch/lot number, if available. More frequent monitoring of liver enzymes as compared to when the medicines are used in monotherapy may be considered. Among the 304 patients in KEYNOTE-204, there is a subpopulation consisting of 112 patients who failed a transplant before enrolling and 137 who failed 2 or more prior therapies and were ineligible for ASCT at the time of enrolment. In the per-protocol immunogenicity (PP-IMM) analysis set for participants who received Nuvaxovid (n = 191), median age was 40 years (range: 22 to 70 years); 93% (n = 178) were 18 to 64 years old and 7% (n = 13) were aged 65 to 84; 43% were female; 75% were White; 23% were multiracial or from ethnic minorities; and 27% had at least one comorbid condition. 8 0 obj The potential risk of gastrointestinal perforation should be taken into consideration. Placebo on Day 1 every 3 weeks in combination with nab-paclitaxel 100 mg/m2 on Days 1, 8 and 15 every 28 days, or paclitaxel 90 mg/m2 on Days 1, 8, and 15 every 28 days, or gemcitabine 1,000 mg/m2 and carboplatin AUC 2 mg/mL/min on Days 1 and 8 every 21 days. Assessed by BICR using RECIST 1.1, An analysis was performed in KEYNOTE-045 in patients who had PD-L1 CPS < 10 [pembrolizumab: n=186 (69%) vs. chemotherapy: n=176 (65%)] or 10 [pembrolizumab: n=74 (27%) vs. chemotherapy: n=90 (33%)] in both pembrolizumab- and chemotherapy-treated arms (see Table 22). The Public Assessment Report is a scientific report, written by the MHRA. Fifty-nine percent of the patients with increased ALT received systemic corticosteroids. All study treatments were administered on Day 1 of each 3-week treatment cycle. The Kaplan-Meier curve for EFS and OS are shown in Figures 32 and 33. The GMP guidelines of MHRA are known as Orange Guide. Patients who experience disease progression that precludes definitive surgery or unacceptable toxicity related to KEYTRUDA as neoadjuvant treatment in combination with chemotherapy should not receive KEYTRUDA monotherapy as adjuvant treatment. 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. A subset of 104 participants received a booster dose of Nuvaxovid approximately 6months after receiving Dose2 of the primary series. Colitis resolved in 130 patients, 2 with sequelae. One-sided p-Value based on stratified log-rank test, Patients had PD-L1 expression with a 1% TPS based on the PD-L1 IHC 22C3 pharmDxTM Kit. Extension (Km 2 ) 141. Based on the stratified Cox proportional hazard model, In patients with EC, Grades 3-5 adverse reactions were 89% for pembrolizumab in combination with lenvatinib and 73% for chemotherapy alone. Pembrolizumab in combination with chemotherapy should be used with caution in patients 75 years after careful consideration of the potential benefit/risk on an individual basis (see section 5.1). The study demonstrated a statistically significant improvement in PFS at its pre-specified interim analysis (HR 0.65; 95% CI 0.49, 0.86; p-Value 0.0012) and OS at final analysis for patients with tumour PD-L1 expression CPS 10 randomised to the pembrolizumab in combination with chemotherapy arm compared with placebo in combination with chemotherapy. The primary efficacy outcome measures were PFS assessed by BICR according to RECIST v1.1 and OS. Table includes participants in the active vaccine group only. KEYNOTE-407: Controlled study of combination therapy in squamous NSCLC patients nave to treatment. OS and PFS benefits were observed regardless of PD-L1 expression level. Secondary efficacy outcome measures were duration of response, PFS, and OS. Hypothyroidism occurred in 939 (12.3%) patients, including Grade 2 or 3 cases in 687 (9.0%) and 8 (0.1%) patients, respectively, receiving pembrolizumab. /Contents 25 0 R The dual primary efficacy outcome measures were pathological complete response (pCR) rate and event-free survival (EFS). >> Since pembrolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected. Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration. Pharmacological properties 6. No cases of severe COVID-19 were reported in the 7,020 Nuvaxovid participants compared with 4 cases of severe COVID-19 reported in the 7,019 placebo recipients in the PP-EFF analysis set. Ref: APCSCG/008 South East London Shared Care Prescribing Guideline for zonisamide for the treatment of epilepsy in ADULTS Date of original approval: June 2016 Last reviewed: August 2020 Review approved: October 2020 Next review date: October 2022 (or sooner if evidence or practice changes) The dosing interval for the heterologous booster dose is the same as that authorised for a booster dose of the vaccine used for primary vaccination (see section 5.1). Treatment with pembrolizumab or placebo, both in combination with chemotherapy, continued until RECIST 1.1-defined progression of disease as determined by the investigator, unacceptable toxicity, or a maximum of 24 months. Randomisation was stratified by metastatic status at initial diagnosis, investigator decision to use bevacizumab, and PD-L1 status (CPS < 1 vs. CPS 1 to < 10 vs. CPS 10). Cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving pembrolizumab (see section 4.8). Based on patients with a best objective response as confirmed complete or partial response, Figure 1: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-006 (intent to treat population), Figure 2: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-006 (intent to treat population), KEYNOTE-002: Controlled study in melanoma patients previously treated with ipilimumab. The primary efficacy outcome measures were OS and PFS as assessed by investigator according to RECIST v1.1. Subgroup analyses were performed in KEYNOTE-426 in patients with PD-L1 CPS 1 [pembrolizumab/axitinib combination: n=243 (56%) vs. sunitinib: n=254 (59%)] and CPS < 1 [pembrolizumab/axitinib combination: n=167 (39%) vs. sunitinib: n=158 (37%)]. << Secondary efficacy outcome measures included response duration, PFS, and OS. Since it is known that antibodies can be secreted in human milk, a risk to the newborns/infants cannot be excluded. /Parent 3 0 R Patients were randomised (2:1) to receive one of the following regimens: Pembrolizumab 200 mg with pemetrexed 500 mg/m2 and investigator's choice of cisplatin 75 mg/m2 or carboplatin AUC 5 mg/mL/min intravenously every 3 weeks for 4 cycles followed by pembrolizumab 200 mg and pemetrexed 500 mg/m2 intravenously every 3 weeks (n=410), Placebo with pemetrexed 500 mg/m2 and investigator's choice of cisplatin 75 mg/m2 or carboplatin AUC 5 mg/mL/min intravenously every 3 weeks for 4 cycles followed by placebo and pemetrexed 500 mg/m2 intravenously every 3 weeks (n=206). Card details ( EFS ) of pembrolizumab effective contraception during treatment with pembrolizumab until unacceptable toxicity disease... < < secondary efficacy outcome measures were OS and PFS benefits were observed regardless of pd-l1 expression tested... 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