mhra spc

All study treatments were administered on Day 1 of each 3-week treatment cycle. Of the patients who recovered, 92 (84%) were rechallenged with either pembrolizumab (3%) or axitinib (31%) monotherapy or with both (50%). /Type /Page An analysis was performed in KEYNOTE-048 in patients whose tumours expressed PD-L1 CPS 20 [pembrolizumab plus chemotherapy: n=126 (49%) vs. standard treatment: n=110 (43%) and pembrolizumab monotherapy: n=133 (52%) vs. standard treatment: n=122 (48%)] (see Table 28). It explains how this product was assessed and its authorisation recommended, as well as its conditions of use. Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers. >> In patients treated with pembrolizumab in combination with chemotherapy, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 44.0% for neutrophils decreased, 29.4% for leucocytes decreased, 26.9% for lymphocytes decreased, 22.1% for haemoglobin decreased, 13.2% for platelets decreased, 11.0% for sodium decreased, 7.7% for phosphate decreased, 6.8% for ALT increased, 6.8% for potassium decreased, 6.1% for glucose increased, 5.6% for AST increased, 3.5% for calcium decreased, 3.2% for potassium increased, 2.9% for creatinine increased, 2.2% for albumin decreased, 2.1% for alkaline phosphatase increased, 2.0% for bilirubin increased, 2.0% for calcium increased, 1.3% for prothrombin INR increased, 1.2% for glucose decreased and 0.5% for sodium increased. 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). Patients were enrolled regardless of tumour PD-L1 expression status. Assessment of tumour status was performed every 9 weeks. It is used by healthcare professionals, such as doctors, nurses and pharmacists. Patients with active autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible for the study. The PFS HR (95% CI) for the favourable, intermediate and poor risk groups were 0.81 (0.53, 1.24), 0.69 (0.53, 0.90) and 0.58 (0.35, 0.94), respectively. Factors associated with early deaths were fast progressive disease on prior platinum therapy and liver metastases. `|^v 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. No dose adjustment is needed for patients with mild or moderate hepatic impairment. 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. arthritis (joint swelling, polyarthritis and joint effusion), ee. Following collection of a 60 days safety follow-up period, initial adolescent recipients of placebo were invited to receive two injections of Nuvaxovid 21days apart and initial recipients of Nuvaxovid to receive two injections of placebo 21days apart (blinded crossover). Record the date and time of discard on the vial label. 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). Any unused medicinal product or waste material should be disposed of in accordance with local requirements. A decision should be made whether to discontinue breast-feeding or to discontinue pembrolizumab, taking into account the benefit of breast-feeding for the child and the benefit of pembrolizumab therapy for the woman. Updated efficacy results with a median follow-up time of 45.5 months are summarised in Table 11 and Figures 6 and 7. At the earlier pre-specified final analysis of ORR (median follow-up time of 17.3 months), statistically significant superiority was achieved for ORR comparing pembrolizumab plus lenvatinib with sunitinib, (odds ratio: 3.84 [95% CI: 2.81, 5.26], p-Value< 0.0001). /Type /Catalog 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. 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. 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). Study1 is an ongoing Phase3, multicentre, randomised, observer-blinded, placebo-controlled study with an adult main study conducted in participants 18years of age and older in United States and Mexico, and a paediatric expansion occurring in participants 12 through 17 years of age in the United States. There are no data available on the interchangeability of Nuvaxovid with other COVID-19 vaccines to complete the primary vaccination course. Otherwise treatment should be discontinued. H0: difference in % = 0 versus H1: difference in % > 0, 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). Immune-related adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab. If you use assistive technology (such as a screen reader) and need a Allogeneic HSCT prior to treatment with pembrolizumab. Pembrolizumab doses of 2 mg/kg bw every 3 weeks, 10 mg/kg bw every 3 weeks, and 10 mg/kg bw every 2 weeks were evaluated in melanoma or previously treated NSCLC clinical studies. The median follow-up time was 17.2 months (range: 0.3 to 29.4 months). /CropBox [0 0 595 842] Participants were enrolled across 28 tumour types by primary diagnosis. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic non-small cell lung carcinoma in adults whose tumours express PD-L1 with a 1% TPS and who have received at least one prior chemotherapy regimen. The median time to onset of hyperthyroidism was 1.4 months (range 1 day to 23.2 months). This version is filed (with the CIs review) as the latest version of the SPC in the TMF. Efficacy results by MMR subgroups were consistent with overall study results. * With additional 12 months of follow-up after the pre-specified final analysis for PFS. PDFBox 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). No patients experienced engraftment syndrome post-transplant. Type 1 diabetes mellitus, including diabetic ketoacidosis, has been reported in patients receiving pembrolizumab (see section 4.8). This medicinal product is subject to additional monitoring. Table 33: Efficacy results in KEYNOTE-581. Patients with non-squamous NSCLC could receive pemetrexed maintenance.). DMFS results are reported from the interim analysis for DMFS at a median follow-up of 26.9 months in Table 10 and Figure 5. See section 4.8 for how to report adverse reactions. The study excluded patients with endometrial sarcoma, carcinosarcoma, pre-existing Grade 3 fistula, uncontrolled BP (> 150/90 mmHg), significant cardiovascular impairment or event within previous 12 months, or patients who had active autoimmune disease or a medical condition that required immunosuppression. Assessment of tumour status was performed at Week 6 and Week 12, followed by every 9 weeks thereafter. All but two patients were white. The MHRA-GMDP database contains the following information issued by the MHRA relating to manufacturing and wholesale authorisations and certificates. PFS results were consistent across pre-specified subgroups, MSKCC prognostic groups and PD-L1 tumour expression status. NEW Colors. 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. Pembrolizumab should be withheld or discontinued for Grades 3 or 4 adrenal insufficiency or symptomatic hypophysitis. In patients with HNSCC treated with pembrolizumab in combination with platinum and 5-FU chemotherapy (n=276), the incidence of hypothyroidism was 15.2%, all of which were Grade 1 or 2. Any questions on the content of this database should be addressed to IE&S-IMT@mhra.gov.uk. Patients had PD-L1 expression with a 1% TPS based on the PD-L1 IHC 22C3 pharmDxTM Kit. In Study 3, an ongoing Phase 2a/b randomizsed, observer-blinded, placebo-controlled study, the safety and immunogenicity of booster dose was evaluated in healthy HIV-negative adult participants 18 to 84years of age and medically stable PLWH 18 to 64years of age who were seronegative to SARS-CoV-2 at baseline. One-sided p-Value based on log-rank test, The primary efficacy outcomes were OS and PFS as assessed by BICR using RECIST v1.1. Table 11: Efficacy results in KEYNOTE-054, Figure 6: Kaplan-Meier curve for recurrence-free survival by treatment arm in KEYNOTE-054 (intent to treat population), Figure 7: Kaplan-Meier curve for distant metastasis-free survival by treatment arm in KEYNOTE-054 (intent to treat population). The primary efficacy outcome measure was ORR as assessed by independent review using RECIST 1.1. Best objective response as confirmed complete response or partial response. Alternatively, ALSA operates a bus from Malaga to Seville 4 times a day. Hi, As an academic sponsor we have are routinely reviewing the MHRA website for any changes to SPCs for our sponsored CTIMPs. 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. 23456789, This term also included events reported as influenza-like illness, This term includes both injection site redness and injection site erythema (common). Corticosteroid therapy may be considered. 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. This page includes guidance for pharmaceutical companies and regulators on how to prepare and review summaries of product characteristics (SmPCs) for human medicines. For suspected SJS or TEN, pembrolizumab should be withheld and the patient should be referred to a specialised unit for assessment and treatment. No specific factor(s) associated with early deaths could be identified. Eighty-six percent had two or more prior lines of therapy and 64% had Stage 3 or higher. Hepatitis resolved in 60 patients. Based on patients with a best overall response as complete or partial response, In 20 subjects with ocular melanoma included in KEYNOTE-001, no objective responses were reported; stable disease was reported in 6 patients. Based on the severity and type of the adverse reaction, pembrolizumab should be withheld for Grade 2 or Grade 3 events and corticosteroids administered. No dose adjustment is needed for patients with mild or moderate renal impairment. Visually inspect the contents of the vial for visible particulate matter and/or discolouration prior to administration. The following terms represent a group of related events that describe a medical condition rather than a single event: a. infusion-related reaction (drug hypersensitivity, anaphylactic reaction, anaphylactoid reaction, hypersensitivity, infusion-related hypersensitivity reaction, cytokine release syndrome, and serum sickness), b. hypothyroidism (myxoedema and immune-mediated hypothyroidism), c. adrenal insufficiency (Addison's disease, adrenocortical insufficiency acute, secondary adrenocortical insufficiency), d. thyroiditis (autoimmune thyroiditis, thyroid disorder, and thyroiditis acute), f. hypophysitis (hypopituitarism, lymphocytic hypophysitis), g. type 1 diabetes mellitus (diabetic ketoacidosis), h. myasthenic syndrome (myasthenia gravis, including exacerbation), i. encephalitis (autoimmune encephalitis, noninfective encephalitis), j. Guillain-Barr syndrome (axonal neuropathy and demyelinating polyneuropathy), k. myelitis (including transverse myelitis), l. meningitis aseptic (meningitis, meningitis noninfective), m. uveitis (chorioretinitis, iritis and iridocyclitis), o. vasculitis (central nervous system vasculitis, aortitis, giant cell arteritis), p. pneumonitis (interstitial lung disease, organising pneumonia, immune-mediated pneumonitis, and immune-mediated lung disease), q. abdominal pain (abdominal discomfort, abdominal pain upper and abdominal pain lower), r. colitis (colitis microscopic, enterocolitis, enterocolitis haemorrhagic, autoimmune colitis, and immune-mediated enterocolitis), s. pancreatitis (autoimmune pancreatitis, pancreatitis acute and immune-mediated pancreatitis), t. gastrointestinal ulceration (gastric ulcer and duodenal ulcer), u. hepatitis (autoimmune hepatitis, immune-mediated hepatitis, drug induced liver injury and acute hepatitis), v. cholangitis sclerosing (immune-mediated cholangitis), w. pruritus (urticaria, urticaria papular and pruritus genital), x. rash (rash erythematous, rash follicular, rash macular, rash maculo-papular, rash papular, rash pruritic, rash vesicular and genital rash), y. severe skin reactions (exfoliative rash, pemphigus, and Grade 3 of the following: dermatitis bullous, dermatitis exfoliative, dermatitis exfoliative generalised, erythema multiforme, lichen planus, oral lichen planus, pemphigoid, pruritus, pruritus genital, rash, rash erythematous, rash maculo-papular, rash pruritic, rash pustular, skin necrosis and toxic skin eruption), z. vitiligo (skin depigmentation, skin hypopigmentation and hypopigmentation of the eyelid), aa. 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