Pembrolizumab has not been studied in patients with severe hepatic impairment (see section 4.2). 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. For additional safety information when pembrolizumab is administered in combination, refer to the SmPC for the respective combination therapy components. Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates for male and female participants and racial groups, and across participants with medical comorbidities associated with high risk of severe COVID-19. 701927. An analysis was performed in KEYNOTE-189 in patients who had PD-L1 TPS < 1% [pembrolizumab combination: n=127 (31%) vs. chemotherapy: n=63 (31%)], TPS 1-49% [pembrolizumab combination: n=128 (31%) vs. chemotherapy: n=58 (28%)] or 50% [pembrolizumab combination: n=132 (32%) vs. chemotherapy: n=70 (34%)] (see Table 15). Assessment of tumour status was performed at 12 weeks, then every 6 weeks through Week 48, followed by every 12 weeks thereafter. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-024, a multicentre, open-label, controlled study for the treatment of previously untreated metastatic NSCLC. Among patients with BRAF mutant tumours, 139 (46%) were previously treated with a BRAF inhibitor. Such treatment The use of this vaccine should be in accordance with official recommendations. The guidance, prepared by the Agency's SmPC Advisory Group, outlines the principles in the European Commission's guideline on SmPC. There are no data on the use of pembrolizumab in pregnant women. In KEYNOTE-042, a higher number of deaths within 4 months of treatment initiation followed by a long-term survival benefit was observed with pembrolizumab monotherapy compared to chemotherapy (see section 5.1). At a pre-specified interim analysis, the median follow-up time for all patients was 37.8 months (range: 2.7-48 months). At the time of this analysis, the Delta (B.1.617.2 and AY lineages) variant of concern (VOC) was the predominant variant circulating in the US and accounted for all cases from which sequence data are available (11/20, 55%). /MediaBox [0 0 595 842] /Resources 22 0 R Assessment of tumour status was performed at 9 weeks, then every 6 weeks through Week 52, followed by every 9 weeks through 24 months. No case of overdose has been reported.
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. 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. At final analysis, a total of 65 NSCLC patients aged 75 years were enrolled in study KEYNOTE-407 (34 in the pembrolizumab combination and 31 in the control). * Hazard ratio (pembrolizumab compared to ipilimumab) based on the stratified Cox proportional hazard model,
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. /CropBox [0 0 595 842] Extension (Km 2 ) 141. Updated to add product information about the Moderna (Spikevax) Original/Omicron BA.4/5 vaccine. The key eligibility criteria for this study were locally advanced, inflammatory, or early-stage TNBC at high risk of recurrence (tumour size > 1 cm but 2 cm in diameter with nodal involvement or tumour size > 2 cm in diameter regardless of nodal involvement), regardless of tumour PD-L1 expression. Ninety-three percent had M1 disease. Of these, 48 out of 61 (79%) were identified as Variants of Concern or Variants of Interest. All study medications were administered as an intravenous infusion. It explains how to use and prescribe a medicine. Disease characteristics were squamous (18%) and non-squamous (82%); M1 (99%); and brain metastases (9%). It will take only 2 minutes to fill in. Administration of Nuvaxovid in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and fetus. Patients randomised to chemotherapy were offered pembrolizumab at the time of disease progression. Note: toxicity grades are in accordance with National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4). Secondary efficacy outcome measures included response duration, PFS, and OS. Of these patients, 55% had no recurrence of ALT > 3 times ULN, and of those patients with recurrence of ALT > 3 times ULN, all recovered. Patients were randomised (1:1:1) to one of the following treatment arms: pembrolizumab 200 mg intravenously every 3 weeks up to 24 months in combination with lenvatinib 20 mg orally once daily. Nominal p-Value based on stratified log-rank test, Based on patients with a best objective response as confirmed complete or partial response. A total of 827 patients were enrolled and randomised to pembrolizumab in combination with lenvatinib (n=411) or investigator's choice of doxorubicin (n=306) or paclitaxel (n=110). >> Randomisation was stratified by geographic region (North America versus Western Europe versus Rest of the World) and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic groups (favourable versus intermediate versus poor). search for MHRA Yellow Card in the Google Play or Apple App Store. At final analysis, a total of 57 NSCLC patients aged 75 years were enrolled in study KEYNOTE-189 (35 in the pembrolizumab combination and 22 in the control). o Followed by four additional cycles of neoadjuvant pembrolizumab 200 mg every 3 weeks or placebo on Day 1 of cycles 5-8 of treatment regimen in combination with: Doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 every 3 weeks on Day 1 of cycles 5-8 of treatment regimen and, Cyclophosphamide 600 mg/m2 every 3 weeks on Day 1 of cycles 5-8 of treatment regimen. The option to use bevacizumab was by investigator choice prior to randomisation. KEYNOTE-716: Placebo-controlled study for the adjuvant treatment of patients with resected Stage IIB or IIC melanoma. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-010, a multicentre, open-label, controlled study for the treatment of advanced NSCLC in patients previously treated with platinum-containing chemotherapy. Limited data are currently available on response duration following pembrolizumab discontinuation at cycle 35. Assessment of tumour status was performed every 9 weeks. 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. News stories, speeches, letters and notices, Reports, analysis and official statistics, Data, Freedom of Information releases and corporate reports. The primary efficacy outcome measures were OS and PFS as assessed by BICR using RECIST 1.1. Pharmaceutical form 4. Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. EFS was defined as the time from randomisation to the first occurrence of any of the following events: progression of disease that precludes definitive surgery, local or distant recurrence, second primary malignancy, or death due to any cause. 4.9 Overdose Hyperkalaemia. Randomisation was stratified by chemotherapy treatment (paclitaxel or nab-paclitaxel vs. gemcitabine and carboplatin), tumour PD-L1 expression (CPS 1 vs. CPS < 1), and prior treatment with the same class of chemotherapy in the neoadjuvant setting (yes vs. no). Among the 994 patients, the baseline characteristics were: median age of 60 years (range: 25 to 84), 33% age 65 or older; 71% male; and 85% ECOG PS of 0 and 15% ECOG PS of 1. The patient may also choose to report any adverse drug reaction 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). Upon enrolment, participants were stratified by age (18 to 64 years; 65 to 84 years) to receive Nuvaxovid or placebo. PDFBox In patients with a history of allogeneic HSCT, acute GVHD, including fatal GVHD, has been reported after treatment with pembrolizumab. Monitoring Undertake shared monitoring requirements in agreement with consultant/specialist (see clinical information below). You have accepted additional cookies. Bevacizumab 5 mg/kg bw on Day 1 or cetuximab 400 mg/m2 on first infusion, then 250 mg/m2 weekly. Twenty-one percent had received 2 prior systemic regimens in the metastatic setting. /Rotate 0 Kaplan-Meier curves for OS based on the final analysis are shown in Figures 20 and 21. 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. Table 14: Efficacy results in KEYNOTE-189, Pembrolizumab + Pemetrexed + Platinum Chemotherapy, Placebo + Pemetrexed + Platinum Chemotherapy, * A total of 113 patients (57%) who discontinued study treatment in the placebo plus chemotherapy arm crossed over to receive monotherapy pembrolizumab or received a checkpoint inhibitor as subsequent therapy,
The median duration was 3.3 months (range 6 days to 28.2+ months). The median OS was 8.4 months for pembrolizumab compared to 7.1 months for standard treatment. 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). Nephritis has been reported in patients receiving pembrolizumab (see section 4.8). Additional Important Safety Information Local and systemic adverse reactions were more frequently reported after Dose 2 than after Dose 1. Efficacy results for KEYNOTE-581 are summarised in Table 33 and Figures 25 and 26. 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. KEYTRUDA is for single use only. A total of 121/411 (29%) of the pembrolizumab and lenvatinib-treated patients received continued study therapy beyond RECIST-defined disease progression.
Dont include personal or financial information like your National Insurance number or credit card details. /MediaBox [0 0 595 842] We use some essential cookies to make this website work. Table 19 summarises the efficacy results in the subpopulation. The binding antibody response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly with inactivated influenza vaccine. We also use cookies set by other sites to help us deliver content from their services. << Rare cases of SJS and TEN, some of them with fatal outcome, have been observed (see sections 4.2 and 4.4). Secondary efficacy outcome measures included response duration, PFS, and OS. KEYTRUDA, in combination with chemotherapy with or without bevacizumab, is indicated for the treatment of persistent, recurrent, or metastatic cervical cancer in adults whose tumours express PD-L1 with a CPS 1. A 30% reduction in antibody responses to Nuvaxovid was noted as assessed by an anti-spike IgG assay with seroconversion rates similar to participants who did not receive concomitant influenza vaccine (see section 4.5 and section 4.8). Of the pooled reactogenicity data, which includes participants aged 18 years and older enrolled in the two phase 3 studies who received any dose of Nuvaxovid (n=20,055) or placebo (n=10,561), the most frequent adverse reactions were injection site tenderness (75%), injection site pain (62%), fatigue (53%), myalgia (51%), headache (50%), malaise (41%), arthralgia (24%), and nausea or vomiting (15%). It will take only 2 minutes to fill in. KEYTRUDA as monotherapy is indicated for adults with MSI-H or dMMR colorectal cancer in the following settings: - first-line treatment of metastatic colorectal cancer; - treatment of unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy. Microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) cancers. Start typing to retrieve search suggestions. /Contents 27 0 R 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. Pembrolizumab in monotherapy (see section 4.2). Secondary efficacy outcome measures were ORR and response duration, as assessed by BICR using RECIST 1.1. Enrolment was completed in November 2020. Co-administration of Nuvaxovid with inactivated influenza vaccines has been evaluated in a limited number of participants in an exploratory clinical trial sub-study, see section 4.8 and section 5.1. One vial of 4 mL of concentrate contains 100 mg of pembrolizumab. Search for information about medicines including patient information leaflets (PILs), details on how the medicine can be used (SmPCs) and scientific reports (PARs). 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. Hyperthyroidism resolved in 315 (79.9%) patients, 11 with sequelae. A partnership between NHS organisations in South East London: Bexley, Bromley, Greenwich, Lambeth, Lewisham and Southwark Clinical Commissioning Groups (CCGs) and GSTFT/KCH /SLAM/ Oxleas NHS Foundation Trusts/Lewisham & Greenwich NHS Trust The efficacy, safety, and immunogenicity of the vaccine has been assessed in a limited number of immunocompromised individuals. The concentrate is a clear to slightly opalescent, colourless to slightly yellow solution. 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. The study demonstrated a statistically significant improvement in OS and PFS for all pre-specified study populations. For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. No clinical data are available on the possible effects of pembrolizumab on fertility. 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. Table 21: Response to pembrolizumab 200 mg every 3 weeks in patients with urothelial carcinoma previously treated with chemotherapy in KEYNOTE-045, Number (%#) of patients with duration 6 months, Number (%#) of patients with duration 12 months,
15 0 obj Based on Kaplan-Meier estimates; includes 84 patients with response of 6 months or longer. Table 13: Efficacy results (PD-L1 TPS 50%) in KEYNOTE-042, Figure 10: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-042 (patients with PD-L1 expression TPS 50%, intent to treat population). Braf inhibitor bw on Day 1 or cetuximab 400 mg/m2 on first infusion, then 250 mg/m2 weekly no data... Or partial response 595 842 ] Extension ( Km 2 ) 141 us deliver content their. Significant improvement in OS and PFS for all pre-specified study populations data on the final are.: Placebo-controlled study for the concomitant therapies information about the Moderna ( Spikevax ) Original/Omicron BA.4/5 vaccine the efficacy... Treatment of patients with a BRAF inhibitor hyperthyroidism resolved in 315 ( 79.9 % ),! Were more frequently reported after treatment with pembrolizumab until disease progression or unacceptable toxicity,,... 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