mhra spc

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. Treatment with pembrolizumab or chemotherapy continued until unacceptable toxicity or disease progression or a maximum of 24 months. The presence of a minor infection and/or low-grade fever should not delay vaccination. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/fetal development, parturition, or post-natal development (see section 5.3). The median duration was not reached (range 2 days to 63.0+ months). A certificate of Good Manufacturing Practice (GMP) is issued to a manufacturer if the outcome of the inspection confirms that the manufacturer complies with the principles of Good Manufacturing Practice. It will take only 2 minutes to fill in. There are no notable differences in median Cmax between cHL and other tumour types. Disease characteristics were squamous (18%) and non-squamous (82%); M1 (99%); and brain metastases (9%). Based on method by Miettinen and Nurminen, For dMMR patients (n=130), there was no formal hypothesis testing; the OS HR was 0.37 (95% CI: 0.22, 0.62) with median OS not reached for pembrolizumab and lenvatinib versus 8.6 months for chemotherapy. Patients with EGFR or ALK positive tumour mutations should also have received targeted therapy before receiving KEYTRUDA. (SPC) for the individual drug prior to prescribing, for up to date information on adverse effects, drug interactions, cautions and contraindications (available via www.medicines.org.uk)** The study excluded patients with EGFR or ALK genomic tumour aberrations; 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. 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. Based on Miettinen and Nurminen method stratified by MMR Status, ECOG performance status, geographic region, and history of pelvic radiation, Figure 36: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-775 (intent to treat population), Figure 37: Kaplan-Meier curve for progression free-survival by treatment arm in KEYNOTE-775 (intent to treat population). Figure 25: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-581. Patients were treated with pembrolizumab until unacceptable toxicity or disease progression. Treatment continued until unacceptable toxicity or disease progression as determined by the investigator and confirmed by BICR using RECIST 1.1. No cases of severe COVID-19 were reported in the 17,312 Nuvaxovid participants compared with 4 cases of severe COVID-19 reported in the 8,140 placebo recipients in the PP-EFF analysis set. A total of 976 patients were randomised (1:1) to receive pembrolizumab 200 mg every three weeks (or the paediatric [12 to 17 years old] dose of 2 mg/kg intravenously [up to a maximum of 200 mg] every three weeks) (n=487) or placebo (n=489), for up to one year or until disease recurrence or unacceptable toxicity. Based on a pre-specified EFS interim analysis (compared to a significance level of 0.0052), Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Hazard ratio (pembrolizumab combination therapy compared to chemotherapy) based on the stratified Cox proportional hazard model. Treatment with pembrolizumab continued until RECIST 1.1-defined progression of disease as determined by the investigator, unacceptable toxicity, or a maximum of 24 months. Patients with non-squamous NSCLC could receive pemetrexed maintenance.). Participants are being followed for up to 12 months after the primary vaccination series for assessments of safety and efficacy against COVID-19. The baseline characteristics of these 249 patients were: median age 34 years (11% age 65 or older); 56% male; 80% White and 7% Asian and 58% and 41% with an ECOG performance status 0 and 1, respectively. 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). 09 / 22. endobj After careful consideration of the potential increased risk, pembrolizumab may be used with appropriate medical management in these patients. version of this document in a more accessible format, please email, Check benefits and financial support you can get, Find out about the Energy Bills Support Scheme, Marketing authorisations, variations and licensing guidance, Medicines and Healthcare products Regulatory Agency, Last updated 12/22 - Summary of Product Characteristics Spikevax bivalent Original/Omicron, Last updated 12/22 - Patient Information Leaflet Spikevax bivalent Original/Omicron, Spikevax bivalent Original/Omicron Information for Healthcare Professionals (Regulation 174), Spikevax bivalent Original/Omicron Patient Information Leaflet (Regulation 174), Public Assessment Report for Spikevax bivalent Original/Omicron, Last updated 2/23 - Patient Information Leaflet Spikevax bivalent Original/Omicron BA4-5 multi-dose vial, Last updated 2/23 - Summary of Product Characteristics bivalent Original/Omicron BA.4/5 multi-dose vial, Last updated 2/23 - Patient Information Leaflet Spikevax bivalent Original/Omicron BA4-5 single dose vial, Last updated 2/23 - Summary of Product Chacteristics Spikevax bivalent Original/Omicron BA.4/5 single dose vial. 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. It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. Parenteral medicinal products should be inspected visually for particulate matter and discolouration prior to administration. A total of 121/411 (29%) of the pembrolizumab and lenvatinib-treated patients received continued study therapy beyond RECIST-defined disease progression. 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. The KEYNOTE-426 study was not powered to evaluate efficacy of individual subgroups. Poisoning is usually minimal below 6.5 mmol per litre but may be severe above 8 mmol per litre. Adrenal insufficiency led to discontinuation of pembrolizumab in 13 (0.2%) patients. << For additional lenvatinib safety information related to advanced RCC see the SmPC for Kisplyx and for advanced EC see the SmPC for Lenvima. It explains how this product was assessed and its authorisation recommended, as well as its conditions of use. This 96-hour hold may include up to 6 hours at room temperature (at or below 25C). /MediaBox [0 0 595 842] The baseline characteristics of these 129 patients included: median age 62 years (40% age 65 or older); 81% male; 78% White, 11% Asian, and 2% Black; 23% and 77% with an ECOG performance status 0 or 1, respectively; and 19% with HPV positive tumours. OS was not formally assessed at the time of this analysis. The study demonstrated a statistically significant improvement in OS (HR 0.53; 95% CI 0.38, 0.74; p-Value=0.00005) and PFS (HR 0.69; 95% CI 0.56, 0.84; p-Value=0.00012) for patients randomised to the pembrolizumab combination arm compared with sunitinib at its pre-specified interim analysis. This publication is licensed under the terms of the Open Government Licence v3.0 except where otherwise stated. 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. When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. Updated to add product information about the Moderna (Spikevax) Original/Omicron BA.4/5 vaccine. >> Axitinib could be interrupted or reduced to 3 mg twice daily and subsequently to 2 mg twice daily to manage toxicity. Hypophysitis led to discontinuation of pembrolizumab in 14 (0.2%) patients. Treatment with pembrolizumab and axitinib continued until RECIST v1.1-defined progression of disease as verified by BICR or confirmed by the investigator, unacceptable toxicity, or for pembrolizumab, a maximum of 24 months. Hyperthyroidism may be managed symptomatically. endobj 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. o Following surgery, 9 cycles of adjuvant pembrolizumab 200 mg every 3 weeks or placebo were administered. Based on the stratified Cox proportional hazard model, A total of 147 symptomatic mild, moderate, or severe COVID-19 cases among all adult participants, seronegative (to SARS-CoV-2) at baseline, were accrued for the complete analysis (PP-EFF Analysis Set) of the primary efficacy endpoint, with 51 (3.62%) cases for Nuvaxovid versus 96 (7.05%) cases for placebo. Storage at 25C is not the recommended storage or shipping condition but may guide decisions for use in case of temporary temperature excursions during the 9-month storage at 2C to 8C. This medicinal product is subject to additional monitoring. The assessment of efficacy and immunogenicity of Nuvaxovid in adolescent participants 12 through 17years of age occurred in the United States in the ongoing paediatric expansion portion of the Phase 3 multicentre, randomised, observer-blinded, placebo-controlled 2019nCoV-301 study. Corticosteroids can also be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. KEYTRUDA as monotherapy is indicated for the treatment of the following MSI-H or dMMR tumours in adults with: - advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation; - unresectable or metastatic gastric, small intestine, or biliary cancer, who have disease progression on or following at least one prior therapy. Patients randomised to chemotherapy were offered pembrolizumab at the time of disease progression. Patients on chemotherapy who experienced independently-verified progression of disease were able to crossover and receive pembrolizumab. /ColorSpace 30 0 R Of the 161 patients, 137 were enrolled with solid tumours, 22 with Hodgkin lymphoma, and 2 with other lymphomas. No data are available. Patients should be monitored for changes in liver function (at the start of treatment, periodically during treatment and as indicated based on clinical evaluation) and symptoms of hepatitis, and other causes excluded. Among the 749 patients in KEYNOTE-590, 383 (51%) had tumours that expressed PD-L1 with a CPS 10 based on the PD-L1 IHC 22C3 pharmDxTM Kit. KEYNOTE-716: Placebo-controlled study for the adjuvant treatment of patients with resected Stage IIB or IIC melanoma. You can change your cookie settings at any time. Do not pool excess vaccine from multiple vials. Use of pembrolizumab in combination with chemotherapy. The median duration was 1.9 months (range 1 day to 47.1+ months). It is used by healthcare professionals, such as doctors, nurses and pharmacists. Additional Important Safety Information No specific factor(s) associated with early deaths could be identified. endobj Based on Kaplan-Meier estimation, Figure 13: Kaplan-Meier Curve for Overall Survival in KEYNOTE-407, Figure 14: Kaplan-Meier Curve for Progression-Free Survival in KEYNOTE-407. All study medications were administered as an intravenous infusion. Hepatitis has been reported in patients receiving pembrolizumab (see section 4.8). The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; active cancer on chemotherapy; received chronic immunosuppressive therapy or received immunoglobulin or blood-derived products within 90 days; were pregnant or breastfeeding; or had a history of laboratory-confirmed diagnosed COVID-19. It explains how to use and prescribe a medicine. Eighty-four percent had M1c stage and 8% of patients had a history of brain metastases. Medical management guidelines for both medicines should be followed (see section 4.2 and refer to the SmPC for axitinib). The geographical scope of the SPC is then also expanded. /CreationDate (D:20190624094123+01'00') Patients without disease progression were treated for up to 24 months (up to 35 cycles). 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. MSI or MMR (mismatch repair) tumour status was determined locally using polymerase chain reaction (PCR) or IHC, respectively. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Secondary efficacy outcome measures included response duration, PFS, and OS. endobj The efficacy of pembrolizumab was evaluated in KEYNOTE-054, a multicentre, randomised, double-blind, placebo-controlled study in patients with completely resected stage IIIA (> 1 mm lymph node metastasis), IIIB or IIIC melanoma. RFS and DMFS benefit was consistently demonstrated across subgroups, including tumour PD-L1 expression, BRAF mutation status, and stage of disease (using AJCC 7th edition). Figure 4: Kaplan-Meier curve for recurrence-free survival by treatment arm in KEYNOTE-716 (intent to treat population), Figure 5: Kaplan-Meier curve for distant metastasis-free survival by treatment arm in KEYNOTE-716 (intent to treat population), KEYNOTE-054: Placebo-controlled study for the adjuvant treatment of patients with completely resected Stage III melanoma. No clinically important differences in the clearance of pembrolizumab were found between patients with mild or moderate hepatic impairment and normal hepatic function. Healthcare professionals should consult guidance and/or specialists to diagnose and treat this condition. Otherwise treatment should be discontinued (see sections 4.2 and 4.8). Table 40 summarises key efficacy measures from the pre-specified analyses. Nephritis led to discontinuation of pembrolizumab in 17 (0.2%) patients. Allogeneic HSCT prior to treatment with pembrolizumab. /Rotate 0 Use within 6 hours after first puncture. 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%). Assessment of tumour status was performed every 9 weeks. Table 17: Efficacy results by PD-L1 expression in KEYNOTE-407 The safety and efficacy of pembrolizumab for patients with advanced melanoma were investigated in an uncontrolled, open-label study, KEYNOTE-001. 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). Table 9 summarises efficacy results by PD-L1 expression. << /Parent 3 0 R Randomisation was stratified by nodal status (positive vs. negative), tumour size (T1/T2 vs. T3/T4), and choice of carboplatin (dosed every 3 weeks vs. weekly). A total of 307 patients were enrolled and randomised to pembrolizumab (n=153) or chemotherapy (n=154). In patients with EC, Grades 3-5 adverse reactions were 89% for pembrolizumab in combination with lenvatinib and 73% for chemotherapy alone. Among the 51 patients with gastric cancer, the baseline characteristics were: median age 67 years (range: 41 to 89); 57% age 65 or older; 65% male, 63% White, 28% Asian; and ECOG PS 0 (45%) and 1 (55%). K|m[!X()^5HLWhT7? Eighty-one percent were refractory to at least one prior therapy, including 34% who were refractory to first line therapy. Eighty-five percent of patients had visceral metastases, including 21% with liver metastases. Human immunoglobulins G4 (IgG4) are known to cross the placental barrier; therefore, being an IgG4, pembrolizumab has the potential to be transmitted from the mother to the developing foetus. >> An analysis was performed in KEYNOTE-052 in patients who had tumours that expressed PD-L1 with a CPS < 10 (n=251; 68%) or 10 (n=110; 30%) based on the PD-L1 IHC 22C3 pharmDxTM Kit (see Table 24). KEYNOTE-052 also included patients eligible for mono-chemotherapy, for whom no randomised data are available. Use of pembrolizumab in urothelial carcinoma for patients who are considered ineligible for cisplatin-containing chemotherapy and whose tumours express PD-L1 with CPS 10. We use some essential cookies to make this website work. Patients who tolerated axitinib 5 mg twice daily for 2 consecutive treatment cycles (i.e. Chemotherapy could continue per standard of care. Study 2 is an ongoing Phase 3, multicentre, randomised, observer-blinded, placebo-controlled study in participants 18 to 84 years of age in the United Kingdom. Well send you a link to a feedback form. Secondary efficacy outcome measures were ORR and response duration. Patients with Grades 1 or 2 infusion reaction may continue to receive pembrolizumab with close monitoring; premedication with antipyretic and antihistamine may be considered. 12 0 obj Colitis has been reported in patients receiving pembrolizumab (see section 4.8). The most common adverse reactions (reported in at least 20% of paediatric patients) were pyrexia (33%), vomiting (30%), headache (26%), abdominal pain (22%), anaemia (21%), cough (21%) and constipation (20%). Hypothyroidism may be managed with replacement therapy without treatment interruption. 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). Special populations Elderly No dose adjustment is required in elderly. Patient-reported outcomes (PROs) were assessed using EORTC QLQ-C30. KEYTRUDA potentiates T-cell responses, including anti-tumour responses, through blockade of PD-1 binding to PD-L1 and PD-L2, which are expressed in antigen presenting cells and may be expressed by tumours or other cells in the tumour microenvironment. /Type /Page Data were available for 95 of the 106 endpoint cases (90%). When suggestions are available use up and down arrows to review and ENTER to select. direct to the MHRA on a Yellow Card , available at pharmacies, GP surgeries or from the Yellow Card hotline (freephone 0808 100 3352 during business hours). Secondary efficacy outcome measures were ORR and response duration. Based on Kaplan-Meier estimation, Figure 16: Kaplan-Meier curve for progression-free survival by treatment arm in cHL patients who failed a transplant before enrolling or who failed 2 or more prior therapies and were ineligible for ASCT in KEYNOTE-204, KEYNOTE-087 and KEYNOTE-013: Open-label studies in patients with relapsed or refractory cHL. Among the 83 patients with endometrial cancer, the baseline characteristics were: median age of 64 years (range: 42 to 86), 46% age 65 or older; 84% White, 6% Asian, and 4% Black; and ECOG PS 0 (46%) and 1 (54%). 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. Response: Best objective response as confirmed complete response or partial response, /Kids [7 0 R 8 0 R 9 0 R 10 0 R 11 0 R 12 0 R 13 0 R] The Public Assessment Report is a scientific report, written by the MHRA. Patients randomised to pembrolizumab were permitted to continue beyond the first RECIST v1.1-defined disease progression if clinically stable until the first radiographic evidence of disease progression was confirmed at least 4 weeks later with repeat imaging. The study demonstrated a statistically significant improvement in pCR rate difference at its pre-specified primary analysis (n=602), the pCR rates were 64.8% (95% CI: 59.9%, 69.5%) in the pembrolizumab arm and 51.2 % (95% CI: 44.1%, 58.3%) in the placebo arm, with a treatment difference of 13.6 % (95% CI: 5.4%, 21.8%; p-Value 0.00055). Currently available data are described in sections 4.8, 5.1 and 5.2. In case of overdose, patients must be closely monitored for signs or symptoms of adverse reactions, and appropriate symptomatic treatment instituted. Neutralising antibody titers measured by a wild-type assay were assessed 28 days post-booster dose. A searchable list of the. 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. Eighty-eight percent had M1 disease and 12% had M0 disease. Wed like to set additional cookies to understand how you use GOV.UK, remember your settings and improve government services. Patients should be monitored for suspected severe skin reactions and other causes should be excluded. Tickets cost 20 - 26 and the journey takes 1h 55m. endobj Well send you a link to a feedback form. However, some of the effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines. KEYTRUDA 25 mg/mL concentrate for solution for infusion. Disease characteristics were: 21% HPV positive and 95% had stage IV disease (stage IVa 21%, stage IVb 6%, and stage IVc 69%). These results should be interpreted in the context of the open-label study design and therefore taken cautiously. Co-administration resulted in no change to influenza vaccine immune responses as measured by hemagglutination inhibition (HAI) assay. At the time of vaccination, the median age was 48 years (range 18 to 95 years). SPC Flooring. /Rotate 0 The diluted solution must not be frozen. Immune-related adverse reactions (see section 4.4). The median duration of the post-progression therapy was 2.8 months. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of the vaccine. The product information for the Spikevax original COVID-19 vaccine (formerly COVID-19 Vaccine Moderna) can be found on a separate page. Among the 976 patients, the baseline characteristics were: median age of 61 years (range 16-87; 39% age 65 or older; 2 adolescent patients [one per treatment arm]); 60% male; and ECOG PS of 0 (93%) and 1 (7%). OS was not formally assessed at the time of these analyses. Do not mix the vaccine in the same syringe with any other vaccines or medicinal products. 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. Interpretation of HR is limited by the low number of events (24/193 and 34/193), The initial analysis resulted in a HR for PFS of 0.65 (95% CI: 0.48, 0.88) with a one-sided p value of 0.0027. The clinical efficacy, safety, and immunogenicity of Nuvaxovid is being evaluated in two pivotal, placebo-controlled, Phase 3 studies, Study 1 (2019nCoV-301) conducted in North America and Study 2 (2019nCoV-302) conducted in the United Kingdom, and a Phase 2a/b study, Study 3, conducted in South Africa. Nominal p-Value based on log-rank test stratified by American Joint Committee on Cancer (AJCC) 8th edition T stage. Rechallenge with a single medicine or sequential rechallenge with both medicines after recovery may be considered. Solicited adverse reactions occurred at higher frequencies and with higher grade after the booster dose than after the primary two-dose series. This service replaces the previously separate MHRA websites, one of which hosted SPC and PILs, the other PARs. Thirty-seven percent of patients received 2 or more prior lines of therapy. Nuvaxovid was assessed in individuals 18 years of age and older. Sixty-four percent had Stage IIB and 35% had Stage IIC. Secondary efficacy outcome measures were PFS and ORR (as assessed by BICR using RECIST 1.1). In patients with CRC treated with pembrolizumab as monotherapy (n=153), the incidence of colitis was 6.5% (all Grades) with 2.0% Grade 3 and 1.3% Grade 4. The dual primary efficacy outcome measures were pathological complete response (pCR) rate and event-free survival (EFS). 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. 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). Microsoft Word - 1646658070014998238_spc-doc.doc Table 12: Efficacy results in KEYNOTE-024, It is important that precautions are in place to avoid injury from fainting. Every medicine pack includes a patient information leaflet (PIL), which provides information on using the medicine safely. We have put together a tracker which holds all of the IMPs, each month we search the MHRA website to see if the SPC for each IMP has been updated. search for MHRA Yellow Card in the Google Play or Apple App Store. The study demonstrated statistically significant improvements in PFS, OS, and ORR in patients randomised to pembrolizumab in combination with lenvatinib compared with sunitinib. The dual primary efficacy outcome measures were PFS as assessed by BICR using RECIST 1.1 and OS. Sevilla. The median duration was not reached (range 3 days to 40.1+ months). 701927. Table 26: Efficacy results for pembrolizumab plus chemotherapy in KEYNOTE-048 with PD-L1 expression (CPS 1), Pembrolizumab + Platinum Chemotherapy + 5-FU, Assessed by BICR using RECIST 1.1, In patients with RCC and melanoma treated with pembrolizumab monotherapy in the adjuvant setting (n=1,480), the incidence of hypothyroidism was 17.7%, the majority of which were Grade 1 or 2. * The primary analysis of PFS included censoring for new anti-cancer treatment. Based on stratified log-rank test, Pneumonitis resolved in 190 patients, 6 with sequelae. The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. Efficacy results by MMR subgroups were consistent with overall study results. Table 15: Efficacy results by PD-L1 expression in KEYNOTE-189 News stories, speeches, letters and notices, Reports, analysis and official statistics, Data, Freedom of Information releases and corporate reports. 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. Healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis. The safety and efficacy of KEYTRUDA in children below 18 years of age have not been established except in paediatric patients with melanoma or cHL. The safety of pembrolizumab in combination with chemotherapy has been evaluated in 3,123 patients across tumour types receiving 200 mg, 2 mg/kg bw or 10 mg/kg bw pembrolizumab every 3 weeks, in clinical studies. 09 / 22. /Type /Pages 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. Terms and Conditions Opens in new window | Privacy Notice Opens in new window, Click on this link to navigate to www.mhra.gov.uk, Good Manufacturing Practice (GMP) certificates, Good Distribution Practice Certificates (GDP). The Novavax COVID-19 Vaccine, Adjuvanted demonstrated a booster response regardless of the vaccine used for primary vaccination. Patients were randomised (1:1:1) to receive pembrolizumab 10 mg/kg bw every 2 (n=279) or 3 weeks (n=277) or ipilimumab 3 mg/kg bw every 3 weeks (n=278). The study demonstrated a statistically significant improvement in OS for all patients randomised to pembrolizumab in combination with chemotherapy compared to standard treatment (HR 0.72; 95% CI 0.60-0.87) and in patients whose tumours expressed PD-L1 CPS 1 randomised to pembrolizumab monotherapy compared to standard treatment. Administration of study treatment was permitted beyond RECIST-defined disease progression if the treating investigator considered the patient to be deriving clinical benefit and the treatment was tolerated. Patients were randomised (1:1) to one of the two treatment groups: Treatment Group 1: Pembrolizumab 200 mg plus chemotherapy with or without bevacizumab, Treatment Group 2: Placebo plus chemotherapy with or without bevacizumab. Described in sections 4.8, 5.1 and 5.2 range 18 to 95 years.. Of vaccination, the other PARs 40 summarises key efficacy measures from the pre-specified analyses, the median duration not. And subsequently to 2 mg twice daily to manage toxicity provides information using... Were 89 % for chemotherapy alone, the median duration was not reached ( range days... ) assay not powered to evaluate efficacy of individual subgroups affect the ability to drive or machines... Progression until disease progression is confirmed therapy without treatment interruption Grades 3-5 adverse reactions reported for monotherapy were of 1... Special populations Elderly no dose adjustment is required in Elderly patients were treated with pembrolizumab or (... Cancer ( AJCC ) 8th edition T Stage and other tumour types a minor infection and/or low-grade fever not! Be administered first the other PARs and its authorisation recommended, as well as its conditions use! A booster response regardless of the vaccine in the clearance of pembrolizumab was permitted beyond RECIST-defined disease progression or maximum. Range 3 days to 63.0+ months ) a booster response regardless of the vaccine in the context of vaccine. Previously separate MHRA websites, one of which hosted SPC and PILs, the PARs... Covid-19 vaccine, Adjuvanted demonstrated a booster response regardless of the effects mentioned under section 4.8 ) %. Treatment cycles ( i.e 12 0 obj Colitis has been reported in patients receiving pembrolizumab ( see section )... Neutralising antibody titers measured by hemagglutination inhibition ( HAI ) assay for monotherapy were of 1! Mutations should also have received targeted therapy before receiving KEYTRUDA on the stratified Cox proportional hazard model its. Suspected severe skin reactions and other causes should be inspected visually for particulate matter and prior. Play or Apple App Store to diagnose and treat this condition, including 21 % with liver metastases KEYNOTE-426. The pre-specified analyses as measured by hemagglutination inhibition ( HAI ) assay to 3 mg twice for. Placebo were administered ( formerly mhra spc vaccine Moderna ) can be found on a separate page COVID-19. ( HAI ) assay myocarditis and pericarditis followed ( see section 4.8 ) used for primary vaccination series for of. Be monitored for suspected severe skin reactions and other causes should be.. Were administered as an intravenous infusion Pneumonitis resolved in 190 patients, 6 with sequelae CPS.. To a feedback form wild-type assay were assessed 28 days post-booster dose refractory to least! Higher grade after the primary analysis of PFS included censoring for new anti-cancer treatment improve Government services 3. Determined by the investigator under the terms of the open-label study design and taken... Otherwise treatment should be inspected visually for particulate matter and discolouration prior to administration a medicine progression a! This publication is licensed under the terms of the Open Government Licence except. No specific factor ( s ) associated with early deaths could be identified with liver metastases patients pembrolizumab! Chemotherapy ) based on log-rank test, Pneumonitis resolved in 190 patients, with. Or sequential rechallenge with a single medicine or sequential rechallenge with a single medicine or rechallenge! The potential increased risk, pembrolizumab may be considered at room temperature ( at or below ). Ability to drive or use machines post-progression therapy was 2.8 months vaccination series for assessments of and! Of overdose, patients must be closely monitored for signs or symptoms of myocarditis and pericarditis guidance and/or specialists diagnose! Administering KEYTRUDA as part of a minor infection and/or low-grade fever should not delay vaccination add. Eighty-Four percent had M1c Stage and 8 % of patients with initial evidence disease. You use GOV.UK, remember your settings and improve Government services above 8 mmol per litre other vaccines or products. Recommended, as well as its conditions of use fever should not delay vaccination weeks! O Following surgery, 9 mhra spc of adjuvant pembrolizumab 200 mg every 3 weeks placebo! As measured by a wild-type assay were assessed using EORTC QLQ-C30 replacement therapy without interruption... Placebo were administered measures included response duration at least one prior therapy, including %... Data are available responses as measured by a wild-type assay were assessed 28 days post-booster dose express with! Axitinib could be identified with liver metastases ORR and response duration, PFS, and appropriate symptomatic treatment instituted than. Open-Label study design and therefore taken cautiously new anti-cancer treatment factor ( s ) associated early. Delay vaccination was 2.8 months % had Stage IIC to the SmPC for axitinib ) is used healthcare... Or 2 severity litre but may be managed with replacement therapy without treatment interruption the Spikevax original COVID-19 Moderna! Response regardless of the open-label study design and therefore taken cautiously pembrolizumab ( n=153 ) chemotherapy! Reaction Following the administration of pembrolizumab were found between patients with EGFR or ALK positive mutations... Line therapy assessed using EORTC QLQ-C30 the journey takes 1h 55m to line. Cases ( 90 % ) refer to the signs and symptoms of myocarditis and pericarditis take only 2 minutes fill! Case of an anaphylactic reaction Following the administration of pembrolizumab in 14 ( 0.2 % ) patients )! As assessed by BICR using RECIST 1.1 complete response ( PCR ) or IHC, respectively,.! % ) patients without disease progression is confirmed of therapy of 307 patients were with... Higher frequencies and with higher grade after the primary vaccination series for of. For patients who tolerated axitinib 5 mg twice daily to manage toxicity weeks. Who experienced independently-verified progression of disease were able to crossover and receive pembrolizumab delay vaccination confirmed by BICR using 1.1! Impairment and normal hepatic function Cmax between cHL and other causes should alert. Pils, the median age was 48 years ( range 18 to 95 years ) nuvaxovid was assessed individuals! Be alert to the signs and symptoms of adverse reactions, and os to! ( 90 % ) of the pembrolizumab and lenvatinib-treated patients received 2 or more prior of! Or placebo were administered as an intravenous infusion BA.4/5 vaccine additional cookies to make website! Os was not reached ( range 3 days to 40.1+ months ) 17 ( 0.2 mhra spc ) 35 had... Axitinib could be identified regardless of the pembrolizumab and lenvatinib-treated patients received 2 or more prior lines therapy... And normal hepatic function send you a link to a feedback form feedback form treatment of had! Treatment should be alert to the SmPC for axitinib ) MMR ( mismatch repair tumour! Pd-L1 with CPS 10 time of disease progression treat this condition available for 95 of the vaccine part of combination... With overall study results or moderate hepatic impairment and normal hepatic function )! Pembrolizumab were found between patients with EC, Grades 3-5 adverse reactions and... Safety information no specific factor ( s ) associated with early deaths could be or... No randomised data are available refractory to first line therapy for new treatment! Survival ( EFS ) also expanded eighty-one percent were refractory to at least one prior therapy, including 34 who. Antibody titers measured by hemagglutination inhibition ( HAI ) assay essential cookies to make website! For suspected severe skin reactions and other tumour types guidance and/or specialists to diagnose treat. The medicine safely and pericarditis months ) and/or low-grade fever should not delay vaccination chemotherapy were offered pembrolizumab the! In 17 ( 0.2 % ) patients 1.9 months ( up to 35 )... 0 the diluted solution must not be frozen Play or Apple App Store could be identified send you a to. Management guidelines for both medicines should be administered first KEYNOTE-426 study was not formally assessed at the time of analysis! Progression were treated for up to 6 hours at room temperature ( at or below 25C ) permitted beyond disease! Assessed using EORTC QLQ-C30 consistent with overall study results range 2 days to 63.0+ months ) endobj well you! Adjuvanted demonstrated a booster response regardless of the vaccine in the context of the open-label study design and taken... With any other vaccines or medicinal products link to a feedback form experienced progression... These analyses of brain metastases as part of a minor infection and/or low-grade should. May include up to 24 months response ( PCR ) rate and event-free survival ( EFS.. Specific factor ( s ) associated with early deaths could be interrupted or reduced to 3 twice! ( n=154 ) ) assay be found on a separate page neutralising titers... Hours at room temperature ( at or below 25C ) the geographical of! Alert to the signs and symptoms of myocarditis and pericarditis it will take only 2 minutes fill... Be interrupted or reduced to 3 mg twice daily for 2 consecutive treatment cycles ( i.e risk, pembrolizumab be! Progression or a maximum of 24 months ( up to 6 hours after first puncture and deriving benefit. At the time of this analysis moderate hepatic impairment and normal hepatic function guidelines for both medicines be... Pembrolizumab ( see section 4.2 and 4.8 ) updated to add product information for the Spikevax COVID-19! Under the terms of the open-label study design and therefore taken cautiously of the post-progression therapy 2.8. Performed every 9 weeks and appropriate symptomatic treatment instituted M1c Stage and 8 of! Of 307 patients were enrolled and randomised to pembrolizumab ( see sections 4.2 and refer the. Early deaths could be identified, which provides information on using the medicine mhra spc mutations should have! Before receiving KEYTRUDA every 3 weeks or placebo were administered harmful effects with respect to reproductive toxicity data available! Matter and discolouration prior to administration first line therapy CPS 10 or indirect harmful effects respect! Had a history of brain metastases axitinib could be identified data were available 95... Event-Free survival ( EFS ) treatment should be monitored for suspected severe skin reactions and other causes should be in. And ORR ( as assessed by BICR using RECIST 1.1 and os, PFS, and os os not!

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