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), A subset of 105 participants (Safety Analysis Set) were randomiszed to receive a booster dose of Nuvaxovid approximately 6months after receiving Dose2 of the primary series and received at least 1 dose of study vaccine; 104 of the 105 participants received Nuvaxovid (Full Analysis Set). Since inspections of manufacturers of active substances are based on risk, some active substance manufacturers may not be in possession of a GMP certificate. /Parent 3 0 R 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. Visually inspect the contents of the vial for visible particulate matter and/or discolouration prior to administration. If not used immediately, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at 2C to 8C. PD-L1 expression was tested retrospectively by immunohistochemistry (IHC) assay with the 22C3 anti-PD-L1 antibody. musculoskeletal pain (musculoskeletal discomfort, back pain, musculoskeletal stiffness, musculoskeletal chest pain and torticollis), cc. 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. Table 41: Efficacy results in KEYNOTE-355 patients with CPS 10, * Chemotherapy: paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin, Pituitary function and hormone levels should be monitored to ensure appropriate hormone replacement. The median number of prior lines of therapy administered for the treatment of cHL was 5 (range 2 to 15). In subgroup analyses, a reduced survival benefit of pembrolizumab compared to docetaxel was observed for patients who were never-smokers or patients with tumours harbouring EGFR activating mutations who received at least platinum-based chemotherapy and a tyrosine kinase inhibitor; however, due to the small numbers of patients, no definitive conclusions can be drawn from these data. These reactions are presented by system organ class and by frequency. 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. You have rejected additional cookies. This is based on the Summary of Product Characteristics of the product. 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%). Table 6: Efficacy results by BRAF mutation status in KEYNOTE-002, * Hazard ratio (pembrolizumab compared to chemotherapy) based on the stratified Cox proportional hazard model. Safety and immunogenicity of COVID-19 vaccines given as a third dose (booster) following completion of a primary vaccination series with another authorizsed COVID-19 vaccine in the UK. PD-L1 expression was tested retrospectively by IHC assay with the 22C3 anti-PD-L1 antibody; 84% of patients had PD-L1-positive melanoma (PD-L1 expression in 1% of tumour and tumour-associated immune cells relative to all viable tumour cells). The study demonstrated a statistically significant improvement in PFS (HR 0.60; 95% CI 0.45, 0.80; p-Value 0.0002) for patients randomised to the pembrolizumab arm compared with chemotherapy at the pre-specified final analysis for PFS. Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo. Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. 13 0 obj Paclitaxel 175 mg/m2 + cisplatin 50 mg/m2 + bevacizumab 15 mg/kg, 3. The baseline characteristics of these 383 patients were: median age of 63 years (range: 28 to 89), 41% age 65 or older; 82% male; 34% White and 56% Asian; 43% and 57% had an ECOG performance status of 0 and 1, respectively. 2, Based on Log-linear model of occurrence using modified Poisson regression with logarithmic link function, treatment group and strata (age-group and pooled region) as fixed effects and robust error variance [Zou 2004]. Safety data were collected in 2,232 participants 12 through 17 years of age, with and without evidence of prior SARS CoV-2 infection, in United States who received at least one dose of Nuvaxovid (n=1,487) or placebo (n=745). 09 / 22. For the neoadjuvant and adjuvant treatment of TNBC, patients should be treated with neoadjuvant KEYTRUDA in combination with chemotherapy for 8 doses of 200 mg every 3 weeks or 4 doses of 400 mg every 6 weeks or until disease progression that precludes definitive surgery or unacceptable toxicity, followed by adjuvant treatment with KEYTRUDA as monotherapy for 9 doses of 200 mg every 3 weeks or 5 doses of 400 mg every 6 weeks or until disease recurrence or unacceptable toxicity. Response was assessed in KEYNOTE-087 and KEYNOTE-013 every 12 and 8 weeks, respectively, with the first planned post-baseline assessment at Week 12. 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). 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. The study population characteristics were: median age of 62 years (range: 26 to 90); 38% age 65 or older; 73% male; 79% White and 16% Asian; 80% had a Karnofsky Performance Score (KPS) 90-100 and 20% had KPS 70-80; patient distribution by IMDC risk categories was 31% favourable, 56% intermediate and 13% poor. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions (see section 4.4). The clinical significance of this is unknown. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-002, a multicentre, double-blind, controlled study for the treatment of advanced melanoma in patients previously treated with ipilimumab and if BRAF V600 mutation-positive, with a BRAF or MEK inhibitor. Of these, 48 out of 61 (79%) were identified as Variants of Concern or Variants of Interest. Based on the severity of the adverse reaction, pembrolizumab should be withheld for Grade 3 skin reactions until recovery to Grade 1 or permanently discontinued for Grade 4 skin reactions, and corticosteroids should be administered (see section 4.2). Altitude above sea level (m) 7. approximate 96-fold increase in neutralizsing antibodies from a GMT of 63 pre-booster (Day 189) to a GMT of 6,023 post-booster (Day 217) and an approximate 4.1-fold increase from a peak GMT (14 days post-Dose 2) of 1,470. It is recommended to administer the second dose 3 weeks after the first dose (see section 5.1). Consistent with a limited extravascular distribution, the volume of distribution of pembrolizumab at steady-state is small (~6.0 L; CV: 20%). >> More frequent monitoring of liver enzymes as compared to when the medicines are used in monotherapy may be considered. /Metadata 2 0 R Marketing authorisation holder 8. The efficacy of pembrolizumab in combination with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab, was investigated in KEYNOTE-826, a multicentre, randomised, double-blind, placebo-controlled study that enrolled 617 patients with persistent, recurrent, or first-line metastatic cervical cancer who had not been treated with chemotherapy except when used concurrently as a radio-sensitising agent. Among the study population (355 patients in the pembrolizumab with lenvatinib arm and 357 in the sunitinib arm), the baseline characteristics were: median age of 62 years (range: 29 to 88 years), 41% age 65 or older; 74% male; 75% White, 21% Asian, 1% Black, and 2% other races; 17% and 83% of patients had a baseline KPS of 70 to 80 and 90 to 100, respectively; patient distribution by IMDC risk categories was 33% favourable, 56% intermediate and 10% poor, and by MSKCC prognostic groups was 27% favourable, 64% intermediate and 9% poor. Randomisation was stratified by tumour PD-L1 expression (TPS 50% or < 50%), HPV status (positive or negative), and ECOG PS (0 vs. 1). The efficacy of pembrolizumab was investigated in KEYNOTE-087 and KEYNOTE-013, two multicentre, open-label studies for the treatment of 241 patients with cHL. 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. , Pyrexia 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. Hazard ratio (pembrolizumab combination therapy compared to chemotherapy) based on the stratified Cox proportional hazard model. There is no information on overdose with pembrolizumab. Randomisation was stratified by tumour histology (squamous cell carcinoma vs. adenocarcinoma), geographic region (Asia vs. ex-Asia), and ECOG performance status (0 vs. 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. ECOG performance status 3) considered not eligible for chemotherapy. In patients with RCC and melanoma treated with pembrolizumab monotherapy in the adjuvant setting (n=1,480), the incidence of hyperthyroidism was 10.9%, the majority of which were Grade 1 or 2. Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT), Allogeneic HSCT after treatment with pembrolizumab. Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. 09 / 22. Disease characteristics were squamous (37%) and non-squamous (63%); stage IIIA (0.8%); stage IIIB (9%); stage IV (90%); and treated brain metastases (6%). Since the original supply disruption alert (SDA/2019/005) was issued on 15 October 2019, MHRA investigations have progressed. endobj Forty-seven percent of patients received 2 or more prior lines of therapy. Based on the severity of the adverse reaction, pembrolizumab should be withheld and corticosteroids administered. Every medicine pack includes a patient information leaflet (PIL), which provides information on using the medicine safely. The study demonstrated a statistically significant improvement in OS and PFS for all pre-specified study populations. The Kaplan-Meier curve for OS for the TPS 50% population based on the final analysis is shown in Figure 10. Treatment of cHL was 5 ( range 2 to 15 ) patients received 2 or More prior lines of.... 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