Demographic characteristics were similar among participants who received Nuvaxovid and those who received placebo. Chemotherapy could continue per standard of care. MSI or MMR (mismatch repair) tumour status was determined locally using polymerase chain reaction (PCR) or IHC, respectively. For storage conditions after dilution of the medicinal product, see section 6.3. /Parent 3 0 R Table 12 summarises key efficacy measures for the entire intent to treat (ITT) population. See section 4.8 for how to report adverse reactions. The baseline characteristics of these 548 patients were: median age of 51 years (range: 22 to 82), 16% age 65 or older; 59% White, 18% Asian, and 1% Black; 37% Hispanic or Latino; 56% and 43% ECOG performance status of 0 or 1, respectively; 63% received bevacizumab as study treatment; 21% with adenocarcinoma and 5% with adenosquamous histology; for patients with persistent or recurrent disease with or without distant metastases, 39% had received prior chemoradiation only and 17% had received prior chemoradiation plus surgery. EVUSHELD is indicated for the treatment of COVID-19 in adults who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19 (see sections 4.2, 5.1 and 5.2).. /Rotate 0 (SPC) and Patient Information Leaflet (PIL) are followed. Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer. A searchable list of the. The study demonstrated statistically significant improvements in OS and ORR for patients randomised to pembrolizumab as compared to chemotherapy. The median time to onset of severe skin reactions was 3.0 months (range 2 days to 25.5 months). The study excluded patients with autoimmune disease; a medical condition that required immunosuppression; or who had received more than 30 Gy of thoracic radiation within the prior 26 weeks. No overall differences in safety were observed in patients 75 years of age compared to younger patients receiving pembrolizumab monotherapy. /Parent 3 0 R The median time to onset of colitis was 4.3 months (range 2 days to 24.3 months). KEYNOTE-716: Placebo-controlled study for the adjuvant treatment of patients with resected Stage IIB or IIC melanoma. The option to use bevacizumab was by investigator choice prior to randomisation. A total of 121/411 (29%) of the pembrolizumab and lenvatinib-treated patients received continued study therapy beyond RECIST-defined disease progression. When used in combination with pembrolizumab, dose escalation of axitinib above the initial 5 mg dose may be considered at intervals of six weeks or longer (see section 5.1). For Grades 3 or 4 infusion reactions, infusion should be stopped and pembrolizumab permanently discontinued (see section 4.2). Among the 616 patients in KEYNOTE-189, baseline characteristics were: median age of 64 years (49% age 65 or older); 59% male; 94% White and 3% Asian; 43% and 56% ECOG performance status of 0 or 1 respectively; 31% PD-L1 negative (TPS < 1%); and 18% with treated or untreated brain metastases at baseline. Counsel patient to report side effects from amiodarone treatment and to protect skin from sunlight. Of 32 patients in KEYNOTE-087 who proceeded to allogeneic HSCT after treatment with pembrolizumab, 16 patients reported acute GVHD and 7 patients reported chronic GVHD, two of which were fatal. Hepatitis resolved in 60 patients. 11 0 obj /Parent 3 0 R Events of anaphylaxis have been reported with Nuvaxovid vaccines. As with other intramuscular injections, the vaccine should be given with caution in individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder (such as haemophilia) because bleeding or bruising may occur following an intramuscular administration in these individuals. Among KEYNOTE-087 patients, the baseline characteristics were median age 35 years (9% age 65 or older); 54% male; 88% White; and 49% and 51% had an ECOG performance status 0 and 1, respectively. Table 42: Efficacy results in KEYNOTE-775, - Minor change to SmPC text on myo/pericarditis. The primary efficacy outcomes were OS and PFS as assessed by BICR using RECIST v1.1. 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 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. Assessed by BICR according to the IWG 2007 criteria by PET CT scans, Based on patients (n=150) with a response by independent review, Based on patients (n=18) with a response by independent review, # Based on Kaplan-Meier estimation; includes 62 patients with responses of 12 months or longer, Based on Kaplan-Meier estimation; includes 7 patients with responses of 12 months or longer, Based on Kaplan-Meier estimation; includes 37 patients with responses of 24 months or longer, Based on Kaplan-Meier estimation; includes 4 patients with responses of 60 months or longer. The median duration of treatment for pembrolizumab plus lenvatinib was 17.0 months. If the outcome of the inspection is that the manufacturer does not comply, a statement of non-compliance may be issued and entered into MHRA-GMDP. The primary efficacy outcome measure was PFS as assessed by blinded independent central review (BICR) using RECIST 1.1. stream These conditions can develop within just a few days after vaccination and have primarily occurred within 14 days. These results reflect enrolment that occurred during the time period when the B.1.351 (Beta) variant was circulating in South Africa. You have accepted additional cookies. Hazard ratio (pembrolizumab combination therapy compared to chemotherapy) based on the stratified Cox proportional hazard model. Patients treated with KEYTRUDA must be given the patient alert card and be informed about the risks of KEYTRUDA (see also package leaflet). Guidance on Prescribing of LMWH Produced: January 2017 Reviewed: December 2020 Next Review Date: November 2023 Page 4 of 4 Appendix 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). Dose delay or discontinuation (see also section 4.4). Over 15 weeks of follow-up, patients treated with pembrolizumab had stable global health status/QoL, while those treated with investigator's choice chemotherapy had a decline in global health status/QoL. Pneumonitis has been reported in patients receiving pembrolizumab (see section 4.8). 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. Qualitative and quantitative composition 3. 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. Based on the severity of the adverse reaction, pembrolizumab should be withheld and corticosteroids administered. Based on Miettinen and Nurminen method stratified by PD-L1 status, platinum chemotherapy and smoking status, Figure 11: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-189 (intent to treat population), Figure 12: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-189 (intent to treat population). Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and those who received placebo. << We publish scientific assessment reports called a Public Assessment Report (PAR) available for new marketing authorisations granted after 30 October 2005. Persons who experienced severe reactions following the second dose may be more likely to experience severe reactions following the third dose. Two patients experienced hepatic VOD, one of which was fatal. One patient experienced engraftment syndrome post-transplant. A temporary suspension of the 15-minute observation period for children aged 5-11 years remains in place and this will be reviewed on a regular basis. You can also use the A-Z list to find the active substance. A total of 307 patients were enrolled and randomised to pembrolizumab (n=153) or chemotherapy (n=154). endobj A secondary efficacy outcome measure was OS. A total of 861 patients were randomised. Based on patients with a best objective response as confirmed complete or partial response. 09 / 22. Each multidose vial contains a colourless to slightly yellow, clear to mildly opalescent dispersion free from visible particles. 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. Adjuvant Matrix-M containing per 0.5 mL dose: Fraction-A (42.5 micrograms) and Fraction-C (7.5 micrograms) of Quillaja saponaria Molina extract. . 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). At the pre-specified interim analysis with a median follow-up time of 23.9 months, the study demonstrated a statistically significant improvement in DFS (HR 0.68; 95% CI 0.53, 0.87; p-Value = 0.0010) for patients randomised to the pembrolizumab arm compared with placebo. The median time to onset of hypophysitis was 5.9 months (range 1 day to 17.7 months). 4.9 Overdose Hyperkalaemia. Name of the medicinal product 2. Secondary efficacy outcome measures were PFS and ORR (as assessed by BICR using RECIST 1.1). Patients with the following conditions were excluded from clinical studies: active CNS metastases; ECOG PS 2 (except for urothelial carcinoma and RCC); HIV infection, hepatitis B or hepatitis C infection; active systemic autoimmune disease; interstitial lung disease; prior pneumonitis requiring systemic corticosteroid therapy; a history of severe hypersensitivity to another monoclonal antibody; receiving immunosuppressive therapy and a history of severe immune-related adverse reactions from treatment with ipilimumab, defined as any Grade 4 toxicity or Grade 3 toxicity requiring corticosteroid treatment (> 10 mg/day prednisone or equivalent) for greater than 12 weeks. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Withdraw the required volume up to 4 mL (100 mg) of concentrate and transfer into an intravenous bag containing sodium chloride 9 mg/mL (0.9%) or glucose 50 mg/mL (5%) to prepare a diluted solution with a final concentration ranging from 1 to 10 mg/mL. Baseline characteristics and demographics were generally comparable between the pembrolizumab and placebo arms. Based on stratified log-rank test, The primary efficacy outcome measure was ORR as assessed by BICR using RECIST 1.1. sunitinib 50 mg orally, once daily for 4 weeks and then off treatment for 2 weeks. included in other section of SPC. The binding antibody response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly with inactivated influenza vaccine. If rechallenging with axitinib, dose reduction as per the axitinib SmPC may be considered. Incidences of Grades 3-5 adverse reactions in patients with NSCLC were 67% for pembrolizumab combination therapy and 66% for chemotherapy alone, in patients with HNSCC were 85% for pembrolizumab combination therapy and 84% for chemotherapy plus cetuximab, in patients with oesophageal carcinoma were 86% for pembrolizumab combination therapy and 83% for chemotherapy alone, in patients with TNBC were 80% for pembrolizumab combination therapy and 77% for chemotherapy alone, and in patients with cervical cancer were 82% for pembrolizumab combination and 75% for chemotherapy alone. Patients with active infections were excluded from clinical studies and were required to have their infection treated prior to receiving pembrolizumab. >> The primary efficacy outcome measure was OS. Patients were randomised (1:1) to one of the following treatment arms: pembrolizumab 200 mg intravenously every 3 weeks in combination with axitinib 5 mg orally, twice daily. An exploratory subgroup analysis was performed in KEYNOTE-048 in patients whose tumours expressed PD-L1 CPS 1 to < 20 [pembrolizumab plus chemotherapy: n=116 (45%) vs. standard treatment: n=125 (49%) and pembrolizumab monotherapy: n=124 (48%) vs. standard treatment: n=133 (52%)] (see Table 29). These SPC applications are geographically-limited to Northern Ireland, unless/until a separate authorisation is also issued by the MHRA to cover the remainder of the UK, i.e. 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. Secondary efficacy outcome measures were OS and ORR (as assessed by BICR using RECIST 1.1). The efficacy of pembrolizumab was investigated in 355 patients with unresectable or metastatic MSI-H or dMMR non-CRC solid tumours enrolled in a multicentre, non-randomised, open-label Phase II study (KEYNOTE-158), including patients with endometrial, gastric, small intestine, or biliary cancer. Alternatively, adverse events of concern in association with Nuvaxovid can be reported to Novavax at www.NovavaxCovidVaccine.com or via +44 020 3514 1838. The primary efficacy outcome measure was PFS based on BICR using RECIST 1.1. In addition, no safety and efficacy data are available in frailer patients (e.g. 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. The most frequent adverse reactions were injection site tenderness (71%), injection site pain (67%), headache (63%), myalgia (57%), fatigue (54%), malaise (43%), nausea or vomiting (23%), arthralgia (19%) and pyrexia (17%). Colitis resolved in 130 patients, 2 with sequelae. The primary efficacy outcome was PFS and the secondary efficacy outcome measure was ORR, both assessed by BICR according to the 2007 revised International Working Group (IWG) criteria. OS was not formally assessed at the time of this analysis. KEYNOTE-006: Controlled study in melanoma patients nave to treatment with ipilimumab. /MediaBox [0 0 595 842] 5 0 obj In the PP-EFF analysis set for participants who received Nuvaxovid, the median age was 47 years (range: 18 to 95 years); 88% (n = 15,264) were 18 to 64 years old and 12% (n = 2,048) were aged 65 and older; 48% were female; 94% were from the United States and 6% were from Mexico; 76% were White, 11% were Black or African American, 6% were American Indian (including Native Americans) or Alaskan Native, and 4% were Asian; 22% were Hispanic or Latino. Animal fertility studies have not been conducted with pembrolizumab. 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. Assessment of tumour status was performed every 6 weeks through Week 18, every 9 weeks through Week 45 and every 12 weeks thereafter. 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