There are limited data on the safety and efficacy of KEYTRUDA in patients with ocular melanoma (see section 5.1). If specified in the indication, patient selection for treatment with KEYTRUDA based on MSI-H/dMMR tumour status should be confirmed by a validated test (see sections 4.1 and 5.1). EIR SPC Flooring ZXE2002. KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic head and neck squamous cell carcinoma in adults whose tumours express PD-L1 with a 50% TPS and progressing on or after platinum-containing chemotherapy (see section 5.1). Disease subtypes were 81% nodular sclerosis, 11% mixed cellularity, 4% lymphocyte-rich and 2% lymphocyte-depleted. 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. The median number of prior lines of therapy administered for the treatment of cHL was 5 (range 2 to 15). KEYTRUDA has not been studied in patients with severe renal impairment (see sections 4.4 and 5.2). We also use cookies set by other sites to help us deliver content from their services. Animal reproduction studies have not been conducted with pembrolizumab; however, in murine models of pregnancy blockade of PD-L1 signalling has been shown to disrupt tolerance to the foetus and to result in an increased foetal loss (see section 5.3). The absence of a GMP certificate should not be understood as meaning that the active substance manufacturer in question does not comply with GMP. what are you looking for? The safety of Nuvaxovid was evaluated from an interim analysis of pooled data from 5 ongoing clinical trials conducted in Australia, South Africa, the United Kingdom, the United States and Mexico. 701927. >> Pneumonitis led to discontinuation of pembrolizumab in 131 (1.7%) patients. A total of 254 participants (Full Analysis Set) received two doses of Nuvaxovid (0.5mL, 5 micrograms 3weeks apart) as the primary vaccination series. Fever 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. Efficacy results were similar for the 2 mg/kg bw and 10 mg/kg bw pembrolizumab arms. In preclinical murine models, PD-1 plus TKI inhibitors have demonstrated enhanced anti-tumour activity compared to either agent alone. Treatment with pembrolizumab continued until RECIST v1.1-defined progression of disease as determined by the investigator or unacceptable toxicity. Twenty-one percent had received 2 prior systemic regimens in the metastatic setting. Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. Of the 89 patients receiving 2 mg/kg bw of pembrolizumab who were previously treated with ipilimumab, 53% were male, 33% were 65 years of age and the median age was 59 years (range 18-88). Treatment with pembrolizumab and lenvatinib continued until RECIST v1.1-defined progression of disease as verified by BICR, unacceptable toxicity, or for pembrolizumab, a maximum of 24 months. 13 0 obj For additional axitinib safety information for elevated liver enzymes see also section 4.4. Healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis. The primary efficacy outcome measure was OS. The cHL population (n=22) included patients 11 to 17 years of age. 234, Based on log-linear model of PCR-confirmed COVID-19 infection incidence rate using Poisson regression with treatment group and age strata as fixed effects and robust error variance, where VE = 100 (1 relative risk) (Zou 2004). Severe skin reactions led to discontinuation of pembrolizumab in 18 (0.2%) patients. Secondary efficacy outcome measures included response duration, PFS, and OS. If you are unable to complete your LogIn successfully please contact the Adverse Incident Centre for assistance and advice: sabre@mhra.gov.uk or 020 3080 7336. Throughout the clinical trials, an increased incidence of hypertension following vaccination with Nuvaxovid (n=46, 1.0%) as compared to placebo (n=22, 0.6%) was observed in older adults during the 3 days following vaccination. When assessing the PD-L1 status of the tumour, it is important that a well-validated and robust methodology is chosen to minimise false negative or false positive determinations. Pneumonitis resolved in 190 patients, 6 with sequelae. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-052, a multicentre, open-label study for the treatment of locally advanced or metastatic urothelial carcinoma in patients who were not eligible for cisplatin-containing chemotherapy. Updated efficacy results with a median follow-up time of 45.5 months are summarised in Table 11 and Figures 6 and 7. . Based on stratified log-rank test (compared to an alpha boundary of 0.00144), Among patients with BRAF mutant tumours, 139 (46%) were previously treated with a BRAF inhibitor. The Novavax COVID-19 Vaccine, Adjuvanted demonstrated a booster response regardless of the vaccine used for primary vaccination. The initial analysis resulted in a HR for OS of 0.82 (95% CI: 0.67, 1.01) with a one-sided p-Value of 0.0316. ?F} 7N{)"W}^ufImeYXgK'j m*nd801F 4sC@.b#-="pwkb9Ei!W-\:#5gMFyJbPd`(& Dma;}@zqZ+/RwHrGr&iy3gMdyuDT@S0:n@BsRssHsVBT{{V!B Based upon a standard query including bradyarrhythmias and tachyarrhythmias. 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. There were no Grade 5 hepatic events. The primary efficacy outcome measures were OS and PFS as assessed by BICR using RECIST 1.1. Tourist area. The median follow-up time was 11.4 months (range: 0.3 to 26.9 months). Nuvaxovid was assessed in individuals 18 years of age and older. Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. KEYNOTE-052 also included patients eligible for mono-chemotherapy, for whom no randomised data are available. 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 5 summarises key efficacy measures in patients previously treated or nave to treatment with ipilimumab, receiving pembrolizumab at a dose of 2 mg/kg bw based on a minimum follow-up time of 30 months for all patients. The incidences of immune-related adverse reactions were 36.1% all Grades and 8.9% for Grades 3-5 for pembrolizumab monotherapy in the adjuvant setting (n=1,480) and 24.2% all Grades and 6.4% for Grades 3-5 in the metastatic setting (n=5,375). Go to Products website to find information on medicines. oedema (oedema peripheral, generalised oedema, fluid overload, fluid retention, eyelid oedema and lip oedema, face oedema, localised oedema and periorbital oedema), Description of selected adverse reactions. A second dose of the vaccine should not be given to those who have experienced anaphylaxis to the first dose of Nuvaxovid. KEYNOTE-361 is a Phase III, randomised, controlled, open-label clinical study of pembrolizumab with or without platinum-based combination chemotherapy (i.e. Paclitaxel 175 mg/m2 + carboplatin AUC 5 mg/mL/min, 4. Treatment could continue beyond progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. 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%). If rechallenging with axitinib, dose reduction as per the axitinib SmPC may be considered. myositis (myalgia, myopathy, necrotising myositis, polymyalgia rheumatica and rhabdomyolysis), dd. In urothelial carcinoma, a higher number of deaths within 2 months was observed in pembrolizumab compared to chemotherapy (see section 5.1). Working together across Sussex. * Hazard ratio (pembrolizumab compared to ipilimumab) based on the stratified Cox proportional hazard model, Use of pembrolizumab for treatment of patients with advanced or recurrent MSI-H or dMMR endometrial carcinoma. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. The PD-1 receptor is a negative regulator of T-cell activity that has been shown to be involved in the control of T-cell immune responses. sunitinib 50 mg orally once daily for 4 weeks then off treatment for 2 weeks. Patients with BRAF V600E mutant melanoma were not required to have received prior BRAF inhibitor therapy. COVID-19 cases were confirmed by polymerase chain reaction (PCR) through a central laboratory. If SJS or TEN is confirmed, pembrolizumab should be permanently discontinued (see section 4.2). /Filter /FlateDecode [j Efficacy was evaluated for 276 patients from two defined cohorts, one which included patients previously treated with ipilimumab (and if BRAF V600 mutation-positive, with a BRAF or MEK inhibitor) and the other which included patients nave to treatment with ipilimumab. For pMMR patients (n=697), the OS HR was 0.68 (95% CI: 0.56, 0.84), p=0.0001, one-sided; with median OS of 17.4 months for pembrolizumab and lenvatinib versus 12.0 months for chemotherapy. Vaccine efficacy is presented in Table 2. 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. << The additional primary efficacy outcome measure, OS, was not formally assessed at the time of the analysis. Patients with autoimmune disease that required systemic therapy within 2 years of treatment; a medical condition that required immunosuppression; or who had received more than 30 Gy of thoracic radiation within the prior 26 weeks were ineligible. 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. Response: Best objective response as confirmed complete response or partial response, All participants were offered the opportunity to continue to be followed in the study. 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. << The M1 NED category included patients with metastatic disease who had undergone complete resection of primary and metastatic lesions. Table 43: Efficacy results in KEYNOTE-826 for patients with PD-L1 expression (CPS 1), Pembrolizumab 200 mg every 3 weeks plus Chemotherapy* with or without bevacizumab, Placebo plus Chemotherapy* with or without bevacizumab, * Chemotherapy (paclitaxel and cisplatin or paclitaxel and carboplatin), With axitinib, dose reduction as per the axitinib SmPC may be.. Permanently discontinued ( see sections 4.4 and 5.2 ) with axitinib, dose reduction as per the SmPC. And was considered to be involved in the control of T-cell immune responses regardless of the listed... Clinical study of pembrolizumab in 131 ( 1.7 % ) patients was (... 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