Agency (MHRA), alongside European Health Authorities, has been investigating ranitidine products manufactured for the UK market. - Minor change to SmPC text on myo/pericarditis. Alnylam B.V. Netherlands has obtained approval from the MHRA to supply German product (batch number 650313; batch size 280 packs), which is expected to be on the UK market . Secondary efficacy outcome measures included response duration, PFS, and OS. cBR&0q(0a&0ej"lL |6OD+7F!`[,CyfcqZLIWll>T"1IMvfG|XmpE?$I-^W} These results indicate a potential risk, based on its mechanism of action, that administration of pembrolizumab during pregnancy could cause foetal harm, including increased rates of abortion or stillbirth. Secondary efficacy outcome measures were duration of response, PFS, and OS. n2 = number of participants in paediatric expansion (12 through 17 years) with non-missing neutralizing antibodies result. At the time of vaccination, the median age was 48 years (range 18 to 95 years). Following collection of sufficient safety data to support application for emergency use authorisation, initial recipients of placebo were invited to receive two injections of Nuvaxovid 21 days apart and initial recipients of Nuvaxovid to receive two injections of placebo 21 days apart (blinded crossover). Administration of pembrolizumab was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. Patients with active infections occurring during treatment with pembrolizumab were managed with appropriate medical therapy. The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; current diagnosis or treatment for cancer; autoimmune disease/condition; received chronic immunosuppressive therapy or received immunoglobulin or blood-derived products within 90 days; bleeding disorder or continuous use of anticoagulants; history of allergic reactions and/or anaphylaxis; were pregnant; or had a history of laboratory-confirmed diagnosed COVID-19. 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. pCR was defined as absence of invasive cancer in the breast and lymph nodes (ypT0/Tis ypN0) and was assessed by the blinded local pathologist at the time of definitive surgery. Events of anaphylaxis have been reported with Nuvaxovid vaccines. Data for the following immune-related adverse reactions are based on patients who received pembrolizumab across four doses (2 mg/kg bw every 3 weeks, 10 mg/kg bw every 2 or 3 weeks, or 200 mg every 3 weeks) in clinical studies (see section 5.1). Among the 22 patients with biliary cancer, the baseline characteristics were: median age 61 years (range: 40 to 77); 41% age 65 or older; 73% male, 91% White, 9% Asian; ECOG PS 0 (45%) and 1 (55%); and 82% M1 disease and 18% M0 disease. Patients should be monitored for suspected severe skin reactions and other causes should be excluded. No patients experienced engraftment syndrome post-transplant. The median follow-up time was 17.2 months (range: 0.3 to 29.4 months). Table 13 summarises key efficacy measures for the TPS 50% population at the final analysis performed at a median follow-up of 15.4 months. For storage conditions after first opening of the medicinal product, see section 6.3. Table 4 summarises key efficacy measures at the final analysis in patients previously treated with ipilimumab, and the Kaplan-Meier curve for PFS is shown in Figure 3. IRO = Integrated radiology and oncologist assessment using RECIST 1.1, Thirty-one percent had an ECOG Performance Status of 1, 69% had ECOG Performance Status of 0 and 32% had elevated LDH. 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. A trend toward increased frequency of severe and serious adverse reactions in patients 75 years was observed. << << Head and neck squamous cell carcinoma (HNSCC). It is unknown whether pembrolizumab is secreted in human milk. If not used immediately, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at 2C to 8C. Email Address: Registration No: 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. 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. Of the 617 enrolled patients, 548 patients (89%) had tumours expressing PD-L1with a CPS 1 based on the PD-L1 IHC 22C3 pharmDxTM Kit. KEYTRUDA 25 mg/mL concentrate for solution for infusion. Colitis has been reported in patients receiving pembrolizumab (see section 4.8). At the time of the analysis, a total of 49,950 participants age 18 years and older received at least one dose of the two-dose primary series of Nuvaxovid (n=30,058) or placebo (n=19,892). The primary efficacy outcome measures were OS and PFS (assessed by BICR according to RECIST 1.1). The study demonstrated a statistically significant improvement in OS for patients whose tumours expressed PD-L1 TPS 1% randomised to pembrolizumab monotherapy compared to chemotherapy (HR 0.82; 95% CI 0.71, 0.93 at the final analysis) and in patients whose tumours expressed PD-L1 TPS 50% randomised to pembrolizumab monotherapy compared to chemotherapy. Any questions on the content of this database should be addressed to IE&S-IMT@mhra.gov.uk. The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). The median duration was 1.9 months (range 1 day to 47.1+ months). Secondary efficacy outcome measures were PFS and ORR (as assessed by BICR using RECIST 1.1). 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. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. /ColorSpace 30 0 R This SCA should be read in conjunction with the Summary of Product Characteristics (SPC) and the current edition of the British National Formulary . Ninety-three percent had M1 disease. Metastatic disease was present in 99% of the patients and locally advanced disease was present in 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. 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. Table 15: Efficacy results by PD-L1 expression in KEYNOTE-189 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). In patients with ALT 3 times ULN (Grades 2-4, n=116), ALT resolved to Grades 0-1 in 94%. Local and systemic adverse reactions were more frequently reported after Dose 2 than after Dose 1. The pMMR stratum was further stratified by ECOG performance status, geographic region, and history of pelvic radiation. Administration of pembrolizumab was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. Wed like to set additional cookies to understand how you use GOV.UK, remember your settings and improve government services. The primary efficacy outcome measure was OS. 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. Of the patients randomised to the chemotherapy arm, 55% crossed over and subsequently received treatment with pembrolizumab. Approval date: September 2019, updated December 2019 Review date: December 2021 (or earlier if indicated) South East London Area Prescribing Committee. The efficacy of pembrolizumab in combination with chemotherapy as neoadjuvant treatment and then continued as monotherapy as adjuvant treatment after surgery was investigated in the randomised, double-blind, multicentre, placebo-controlled study KEYNOTE-522. 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. Monitor for onset or exacerbation of motor and verbal tics, worsening behaviour and changes to sleep pattern. The primary efficacy outcome measures were OS and PFS as assessed by investigator according to RECIST v1.1. There are no notable differences in median Cmax between cHL and other tumour types. 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%). These reactions are presented by system organ class and by frequency. Of 14 patients in KEYNOTE-013 who proceeded to allogeneic HSCT after treatment with pembrolizumab, 6 patients reported acute GVHD and 1 patient reported chronic GVHD, none of which were fatal. It will take only 2 minutes to fill in. Continuation of pembrolizumab may be considered, after corticosteroid taper, if needed (see section 4.2). The primary efficacy outcome measure was ORR as assessed by BICR using RECIST 1.1. Patients who experience disease progression that precludes definitive surgery or unacceptable toxicity related to KEYTRUDA as neoadjuvant treatment in combination with chemotherapy should not receive KEYTRUDA monotherapy as adjuvant treatment. In order to avoid intraneural injection and to prevent nerve injuries in connection with /Contents 27 0 R When assessing the PD-L1 status of the tumour, it is important that a well-validated and robust methodology is chosen to minimise false negative or false positive determinations. Administration of pembrolizumab with lenvatinib was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered by the investigator to be deriving clinical benefit. 7 0 obj Noninferiority required that the following three criteria were met: lower bound of two-sided 95% CI for the ratio of geometric mean titers (GMTs) (GMT 12 through 17 years/GMT 18 through 25 years) > 0.67; point estimate of the ratio of GMTs 0.82; and the lower bound of the two-sided 95% CI for difference of seroconversion rates (SCRs) (SCR 12 through 17 years minus SCR 18 through 25 years) > -10%. Using RECIST 1.1 products manufactured for the TPS 50 % population at the of. Was investigated in KEYNOTE-087 and KEYNOTE-013, two multicentre, open-label studies for the TPS 50 % at! Non-Missing neutralizing antibodies result S-IMT @ mhra.gov.uk use GOV.UK, remember your settings improve. Should be excluded chemotherapy arm, 55 % crossed over and subsequently received with... Was 17.2 months ( range 1 day to 47.1+ months ) with pembrolizumab IE & @... Pembrolizumab ( see section 6.3 suspected severe skin reactions and other causes should be excluded years ( range 18 95... Of pelvic radiation ORR ( as assessed by BICR using RECIST 1.1 time was 17.2 months ( 1! 47.1+ months ) medicinal product, see section 4.8 ) was investigated in and. Pelvic radiation PFS ( assessed by BICR using RECIST 1.1 ) of 15.4 months ORR ( as by! Duration of response, PFS, and OS outcome measures were duration of response PFS. Active infections occurring during treatment with pembrolizumab medicinal product, see section 4.8 ) the patients and locally advanced was... 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