Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. Severe endocrinopathies, including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism have been observed with pembrolizumab treatment. Patients on chemotherapy who experienced independently-verified progression of disease after the first scheduled disease assessment were able to crossover and receive 2 mg/kg bw or 10 mg/kg bw of pembrolizumab every 3 weeks in a double-blind fashion. Patients must have undergone lymph node dissection, and if indicated, radiotherapy within 13 weeks prior to starting treatment. All rights reserved. News stories, speeches, letters and notices, Reports, analysis and official statistics, Data, Freedom of Information releases and corporate reports, Information for healthcare professionals and the public on Moderna's bivalent vaccines. In the PP-EFF analysis set for participants who received Nuvaxovid, median age was 56.0 years (range: 18 to 84 years); 72% (n = 5,067) were 18 to 64 years old and 28% (n = 1,953) were aged 65 to 84; 49% were female; 94% were White; 3% were Asian; 1% were multiple races, <1% were Black or African American; and <1% were Hispanic or Latino; and 45% had at least one comorbid condition. /ExtGState 32 0 R Figure 25: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-581. OS results were not yet mature with 23 deaths out of 496 patients in the pembrolizumab arm and 43 deaths out of 498 patients in the placebo arm. /Filter /FlateDecode At the pre-specified interim analysis of PFS (median follow-up time of 19.2 months), statistically significant superiority was achieved for PFS comparing pembrolizumab/chemotherapy with placebo/chemotherapy p-Value 0.0012. The Kaplan-Meier curve for OS for the TPS 50% population based on the final analysis is shown in Figure 10. The patient will be provided with the patient alert card with each prescription. Disease characteristics were squamous (18%) and non-squamous (82%); M1 (99%); and brain metastases (9%). * Hazard ratio (pembrolizumab compared to chemotherapy) based on the stratified Cox proportional hazard model, Not statistically significant after adjustment for multiplicity, Based on patients with a best objective response as confirmed complete or partial response from the final analysis, Figure 3: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-002 (intent to treat population), KEYNOTE-001: Open-label study in melanoma patients nave and previously treated with ipilimumab. Expires . 2 0 obj |:S`#0*Dwsk/DTbFAI iJqbn}WQh(03`>+VluoUlu`Dsp n*, Microsoft Word - 1646658070014998238_spc-doc.doc. /CropBox [0 0 595 842] The relationship between body weight and clearance supports the use of either fixed dose or body weight-based dosing to provide adequate and similar control of exposure. Upon enrolment, participants were stratified by age (18 to 64 years; 65 to 84 years) to receive Nuvaxovid or placebo. The baseline characteristics for this population included: median age 63 years (42% age 65 or older); 61% male; 72% White and 21% Asian and 34% and 66% with an ECOG performance status 0 and 1, respectively. Adrenal insufficiency (primary and secondary) has been reported in patients receiving pembrolizumab. A total of 1,174 patients were randomised. Table 39 summarises key efficacy measures from the pre-specified analysis in patients whose tumours expressed PD-L1 with a CPS 10 in KEYNOTE-590 performed at a median follow-up time of 13.5 months (range: 0.5 to 32.7 months). Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. The incidences of immune-related adverse reactions were 36.1% all Grades and 8.9% for Grades 3-5 for pembrolizumab monotherapy in the adjuvant setting (n=1,480) and 24.2% all Grades and 6.4% for Grades 3-5 in the metastatic setting (n=5,375). >> Patients treated with KEYTRUDA must be given the patient alert card and be informed about the risks of KEYTRUDA (see also package leaflet). << Altitude above sea level (m) 7. Hyperthyroidism occurred in 394 (5.2%) patients, including Grade 2 or 3 cases in 108 (1.4%) and 9 (0.1%) patients, respectively, receiving pembrolizumab. The primary efficacy outcome measure was ORR as assessed by BICR using RECIST 1.1. /Resources 16 0 R Any questions on the content of this database should be addressed to IE&S-IMT@mhra.gov.uk. Microsoft Word - 1646658070014998238_spc-doc.doc Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Safety data of pembrolizumab in the adjuvant melanoma setting in patients 75 years are limited. Dose escalation of axitinib to 10 mg twice daily was permitted using the same criteria. The primary efficacy analysis population (referred to as the Per-Protocol Efficacy [PP-EFF] analysis set) included 25,452 participants who received either Nuvaxovid (n = 17,312) or placebo (n = 8,140), received two doses (Dose 1 on day 0; Dose 2 at day 21, median 21 days [IQR 21-23], range 14-60), did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infection through 7 days after the second dose. 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. The median duration was 1.3 months (range 1 day to 29.0+ months). No dose adjustment is necessary in patients 65 years (see sections 4.4 and 5.1). A total of 254 participants (Full Analysis Set) received two doses of Nuvaxovid (0.5mL, 5 micrograms 3weeks apart) as the primary vaccination series. MSI or MMR tumour status was determined prospectively using PCR or IHC, respectively. 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. Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo. Brentuximab vedotin (BV) 1.8 mg/kg bw intravenously every 3 weeks. Frequencies are defined as: very common ( 1/10); common ( 1/100 to < 1/10); uncommon ( 1/1,000 to < 1/100); rare ( 1/10,000 to < 1/1,000); very rare (< 1/10,000); and not known (cannot be estimated from the available data). All but two patients were white. Assessment of tumour status was performed at 9 weeks, then every 6 weeks through Week 52, followed by every 9 weeks through 24 months. It is used by healthcare professionals, such as doctors, nurses and pharmacists. Participants with clinically stable disease, defined as disease not requiring significant change in therapy or hospitalisation for worsening disease during the 4 weeks before enrolment were included. The same scoring system was used for metastatic melanoma (MEL score). Colitis occurred in 158 (2.1%) patients, including Grade 2, 3 or 4 cases in 49 (0.6%), 82 (1.1%) and 6 (0.1%) patients, respectively, receiving pembrolizumab. Administration of pembrolizumab and axitinib was permitted beyond RECIST-defined disease progression if the patient was clinically stable and considered to be deriving clinical benefit by the investigator. The frequencies are based on all reported adverse drug reactions, regardless of the investigator assessment of causality. This page includes guidance for pharmaceutical companies and regulators on how to prepare and review summaries of product characteristics (SmPCs) for human medicines. PLWH were medically stable (free of opportunistic infections), receiving highly active and stable antiretroviral therapy, and having an HIV-1 viral load of < 1000 copies/mL. Patients with active, non-infectious pneumonitis, an allogeneic HSCT within the past 5 years (or > 5 years but with symptoms of GVHD), active autoimmune disease, a medical condition that required immunosuppression, or an active infection requiring systemic therapy were ineligible for the study. This is based on the MHRA assessment report with any commercially or personally confidential information removed. QRjj$HUwg These results were consistent when reclassified in a post-hoc analysis according to the current AJCC 8th edition staging system. 234, Met primary efficacy endpoint criterion for success with a lower bound confidence interval (LBCI) > 30%, efficacy has been confirmed at the interim analysis. Patients with EGFR activation mutation or ALK translocation also had disease progression on approved therapy for these mutations prior to receiving pembrolizumab. In patients treated with pembrolizumab monotherapy, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 9.4% for lymphocytes decreased, 7.4% for sodium decreased, 5.8% for haemoglobin decreased, 5.3% for phosphate decreased, 5.3% for glucose increased, 3.3% for ALT increased, 3.1% for AST increased, 2.6% for alkaline phosphatase increased, 2.3% for potassium decreased, 2.1% for potassium increased, 1.9% for neutrophils decreased, 1.8% for platelets decreased, 1.8% for calcium increased, 1.7% for bilirubin increased, 1.5% for calcium decreased, 1.4% for albumin decreased, 1.3% for creatinine increased, 1.2% for glucose decreased, 0.8% for leucocytes decreased, 0.7% for magnesium increased, 0.5% for sodium increased, 0.4% for haemoglobin increased, and 0.2% for magnesium decreased. 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. 4 mL of concentrate in a 10 mL Type I clear glass vial, with a coated grey chlorobutyl or bromobutyl stopper and an aluminium seal with a dark blue coloured flip-off cap, containing 100 mg pembrolizumab. The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). Twelve percent of patients had BRAF mutations and 36% had RAS mutations; 39% and 34% were undetermined for BRAF and RAS mutations, respectively. COVID-19 Vaccine (recombinant, adjuvanted), This is a multidose vial which contains 10 doses of 0.5 mL. /Type /Page Patients received pembrolizumab 200 mg every 3 weeks (n=210; KEYNOTE-087) or 10 mg/kg bw every 2 weeks (n=31; KEYNOTE-013) until unacceptable toxicity or documented disease progression. % In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6. These results should be interpreted in the context of the open-label study design and therefore taken cautiously. 5 0 obj /ProcSet [/PDF /Text] It is recommended to administer the second dose 3 weeks after the first dose (see section 5.1). Patients with active autoimmune disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible. The median OS was 8.4 months for pembrolizumab compared to 7.1 months for standard treatment. endobj Corticosteroid therapy may be considered. %PDF-1.4 Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; GMR = ratio of GMT, which is defined as the ratio of 2 GMTs for comparison of 2age cohorts; GMT = geometric mean titer; LLOQ = lower limit of quantitation; MN = microneutralisation; N = number of participants in assay-specific PP-IMM Analysis Set in each part of study with non-missing response at each visit; PP-IMM = Per-Protocol Immunogenicity; SARS-CoV-2 = severe acute respiratory syndrome coronavirus2. For additional lenvatinib safety information related to advanced RCC see the SmPC for Kisplyx and for advanced EC see the SmPC for Lenvima. Nephritis led to discontinuation of pembrolizumab in 17 (0.2%) patients. Clear to slightly opalescent, colourless to slightly yellow solution, pH 5.2 5.8. 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. Patients without disease progression could be treated for up to 24 months. The investigator selected one of the following four treatment regimens prior to randomisation: 1. EIR SPC Flooring. Head and neck squamous cell carcinoma (HNSCC). The efficacy of pembrolizumab in combination with paclitaxel, nab-paclitaxel, or gemcitabine and carboplatin was investigated in KEYNOTE-355, a randomised, double-blind, multicentre, placebo-controlled study. /Filter /FlateDecode 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 One-sided p-Value based on stratified log-rank test, endobj All 827 of these patients received prior systemic therapy for EC: 69% had one, 28% had two, and 3% had three or more prior systemic therapies. Pneumonitis occurred more frequently in patients with a history of prior thoracic radiation (8.1%) than in patients who did not receive prior thoracic radiation (3.9%). The secondary outcome measures were distant metastasis-free survival (DMFS) and OS in the whole population. Each vial contains an excess fill of 0.25 mL (total content per vial 4.25 mL) to ensure the recovery of 4 mL of concentrate. Based on method by Miettinen and Nurminen, # Based on patients with a best objective response as confirmed complete or partial response, Czechia, Date of first authorisation: February 2022, Hypertension was not reported in adolescents aged 12 through to 17 years in the clinical study. null Pembrolizumab in monotherapy (see section 4.2). Immediately prior to use, remove the vaccine vial from the carton in the refrigerator. Key eligibility criteria were metastatic non-squamous NSCLC, no prior systemic treatment for metastatic NSCLC, and no EGFR or ALK genomic tumour aberrations. Reasons for cisplatin ineligibility included: baseline creatinine clearance of < 60 mL/min (50%), ECOG performance status of 2 (32%), ECOG performance status of 2 and baseline creatinine clearance of < 60 mL/min (9%), and other (Class III heart failure, Grade 2 or greater peripheral neuropathy, and Grade 2 or greater hearing loss; 9%). Immune-related adverse reactions affecting more than one body system can occur simultaneously. The Kaplan-Meier curve for OS for the TPS 50% population is shown in Figure 22. Secondary efficacy outcome measures included response duration, PFS, and OS. /CropBox [0 0 595 842] British National Formulary accessed online sept 2019 3. Pembrolizumab may be restarted within 12 weeks after last dose of KEYTRUDA if the adverse reaction recovers to Grade 1 and corticosteroid dose has been reduced to 10 mg prednisone or equivalent per day. Treatment with pembrolizumab or placebo, both in combination with chemotherapy, continued until RECIST 1.1-defined progression of disease as determined by the investigator, unacceptable toxicity, or a maximum of 24 months. Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. Nuvaxovid was administered at least 70 days after completion of a ChAdOx1 nCov-19 (OxfordAstraZeneca) primary vaccination series or at least 84 days after completion of a BNT162b2 (PfizerBioNtech) primary vaccination series. Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo. 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. Sixty-three percent had M1c stage and 2% of patients had a history of brain metastases. We also publish Safety Public Assessment Reports, Further information about SPC, PILs and PARs, The leaflets which are provided with medicines, The description of the medicinal products properties and how it can be used, Scientific reports about marketing authorisations for medicines. SPC Flooring. Corticosteroids should be administered for Grade 2 events (initial dose of 1-2 mg/kg/day prednisone or equivalent followed by a taper) and, based on severity of creatinine elevations, pembrolizumab should be withheld for Grade 2, and permanently discontinued for Grade 3 or Grade 4 nephritis (see section 4.2). 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. Table 20: Efficacy results in KEYNOTE-087 and KEYNOTE-013, 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. << 09/24. For efficacy data in patients 75 years of age please refer to the relevant section of each indication. Working together across Sussex. Table 1: Recommended treatment modifications for KEYTRUDA, Withhold until adverse reactions recover to Grades 0-1*, Grade 2 with creatinine > 1.5 to 3 times upper limit of normal (ULN), Grade 2 adrenal insufficiency and hypophysitis, Withhold treatment until controlled by hormone replacement, Grades 3 or 4 adrenal insufficiency or symptomatic hypophysitis, Type 1 diabetes associated with Grade 3 hyperglycaemia (glucose > 250 mg/dL or > 13.9 mmol/L) or associated with ketoacidosis. /Contents 15 0 R Patients who received prior therapy for melanoma other than surgery were ineligible. Both pembrolizumab arms were superior to chemotherapy for PFS, and there was no difference between pembrolizumab doses. 09/24. A Public Assessment Report (PAR) is a scientific assessment report available for marketing authorisations granted after 30 October 2005. Pembrolizumab is administered via the intravenous route and therefore is immediately and completely bioavailable. >> Of the patients who recovered, 92 (84%) were rechallenged with either pembrolizumab (3%) or axitinib (31%) monotherapy or with both (50%). Nodular-sclerosis was the more represented cHL histological subtype (~ 81%) and bulky disease, B symptoms and bone marrow involvement were present in approximately 21%, 28% and 4% of patients, respectively. << KEYNOTE-158: Open-label study in patients with unresectable or metastatic MSI-H or dMMR endometrial, gastric, small intestine, or biliary cancer who have received prior therapy. 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. These studies enrolled patients who failed ASCT and BV, who were ineligible for ASCT because they were unable to achieve a complete or partial remission to salvage chemotherapy and failed BV, or who failed ASCT and did not receive BV. << Participants were enrolled across 28 tumour types by primary diagnosis. Animal fertility studies have not been conducted with pembrolizumab. There is no information on overdose with pembrolizumab. Cisplatin could be administered on Day 2 of each 3-week treatment cycle. The median time to onset of nephritis was 4.2 months (range 12 days to 21.4 months). /Parent 3 0 R Agency (MHRA), alongside European Health Authorities, has been investigating ranitidine products manufactured for the UK market. Physicians should consider the benefit/risk balance of the available treatment options (pembrolizumab monotherapy or pembrolizumab in combination with chemotherapy) before initiating treatment in patients with HNSCC whose tumours express PD-L1 (see section 5.1). No new immune-related adverse reactions were identified in the adjuvant setting. No clinically important differences in the clearance of pembrolizumab were found between patients with mild or moderate renal impairment and patients with normal renal function. You have accepted additional cookies. Based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by nodal status, tumour size, and choice of carboplatin, # One-sided p-Value based on log-rank test stratified by nodal status, tumour size, and choice of carboplatin. << 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. myositis (myalgia, myopathy, necrotising myositis, polymyalgia rheumatica and rhabdomyolysis), dd. Patients were treated with pembrolizumab until unacceptable toxicity or disease progression. Both studies included patients regardless of PD-L1 expression. A total of 559 patients were randomised. Immune-related severe skin reactions occurred in 130 (1.7%) patients, including Grade 2, 3, 4 or 5 cases in 11 (0.1%), 103 (1.3%), 1 (< 0.1%) and 1 (< 0.1%) patients, respectively, receiving pembrolizumab. Do not administer the vaccine if either are present. It is not intended to provide practical advice on how to use this product. Use of pembrolizumab for first-line treatment of patients with HNSCC. EMC Summary of Product Characteristics for Neoral accessed online sept 2019 2. Events of anaphylaxis have been reported with Nuvaxovid vaccines. Scientific guidelines with SmPC recommendations. These reactions are presented by system organ class and by frequency. Grades 3-5 adverse reactions in patients with RCC were 80% for pembrolizumab in combination with either axitinib or lenvatinib and 71% for sunitinib alone. 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. ?%Kb^V8=/06%z~F0mbXZIs#MA` _w]?c/V)UFq`Gs^ 8O MAi)insr#W"RkV nl~{>~Y N.r}TD=G XwsB{`@u.1prC[N -RbEY;/3&^t! In these paediatric patients with cHL, the ORR assessed by BICR according to the IWG 2007 criteria was 54.5%, 1 patient (4.5%) had a complete response and 11 patients (50.0%) had a partial response, and the ORR assessed by the Lugano 2014 criteria was 63.6%, 4 patients (18.2%) had a complete response and 10 patients (45.5%) had a partial response. The primary efficacy outcome measures were OS and PFS as assessed by BICR using RECIST 1.1. Local and systemic adverse reactions were more frequently reported after Dose 2 than after Dose 1. This 96-hour hold may include up to 6 hours at room temperature (at or below 25C). This vaccine contains potassium, less than 1 mmol (39 mg) per dose, that is to say, essentially potassium-free. Paclitaxel 175 mg/m2 + carboplatin AUC 5 mg/mL/min, 4. 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. This product is considered high in sodium. One-sided p-Value based on log-rank test, BMI 30 kg/m2, chronic lung disease, diabetes mellitus type 2, cardiovascular disease, and chronic kidney disease). In patients with cHL, the incidence of pneumonitis (all Grades) ranged from 5.2% to 10.8% for cHL patients in KEYNOTE-087 (n=210) and KEYNOTE-204 (n=148), respectively. << 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. Appropriate medical treatment and supervision should always be readily available in case of an anaphylactic reaction following the administration of the vaccine. sunitinib 50 mg orally, once daily for 4 weeks and then off treatment for 2 weeks. Patients were stratified by PD-L1 expression (TPS 50%), HPV status and ECOG performance status and then randomised (1:1) to receive either pembrolizumab 200 mg every 3 weeks (n=247) or one of three standard treatments (n=248): methotrexate 40 mg/m2 once weekly (n=64), docetaxel 75 mg/m2 once every 3 weeks (n=99), or cetuximab 400 mg/m2 loading dose and then 250 mg/m2 once weekly (n=71). Individuals may not be fully protected until 7 days after their second dose. 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). ECOG performance status 3) considered not eligible for chemotherapy. EIR SPC Flooring ZXE2002. >> From a microbiological point of view, after first opening (first needle puncture), the vaccine should be used immediately. The primary efficacy outcome measure was OS. PFS results were consistent across pre-specified subgroups, MSKCC prognostic groups and PD-L1 tumour expression status. Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. No clinical data are available on the possible effects of pembrolizumab on fertility. This updated OS analysis was not adjusted to account for subsequent therapies. 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). Treatment with pembrolizumab or placebo continued until RECIST 1.1-defined progression of disease as determined by BICR, unacceptable toxicity, or a maximum of 24 months. You have accepted additional cookies. Not statistically significant after adjustment for multiplicity, Figure 28: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-177 (intent to treat population), Figure 29: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-177 (intent to treat population), * Not statistically significant after adjustment for multiplicity, KEYNOTE-164: Open-label study in patients with unresectable or metastatic MSI-H or dMMR CRC who have received prior therapy. Among these 548 enrolled patients with tumours expressing PD-L1, 273 patients were randomised to pembrolizumab in combination with chemotherapy with or without bevacizumab, and 275 patients were randomised to placebo in combination with chemotherapy with or without bevacizumab. Assessment of tumour status was performed at Week 9 and then every 6 weeks for the first year, followed by every 9 weeks through 24 months. Pharmaceutical form 4. The efficacy of pembrolizumab was investigated in KEYNOTE-164, a multicentre, non-randomised, open-label, multi-cohort Phase II study that enrolled patients with unresectable or metastatic MSI-H or dMMR CRC that progressed following prior fluoropyrimidine-based therapy in combination with irinotecan and/or oxaliplatin. KEYNOTE-716: Placebo-controlled study for the adjuvant treatment of patients with resected Stage IIB or IIC melanoma. 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. 12 0 obj After careful consideration of the potential increased risk, pembrolizumab may be used with appropriate medical management in these patients. endobj We publish the most up-to-date information for a medicine according to its licence history. Patients with non-squamous NSCLC could receive pemetrexed maintenance.). Eighty-one percent were refractory to at least one prior therapy, including 34% who were refractory to first line therapy. Hypothyroidism led to discontinuation of pembrolizumab in 6 (0.1%) patients. Assessment of tumour status was performed at baseline, after randomisation at Week 12, then every 6 weeks thereafter until Week 54, and then every 12 weeks thereafter. Among the 542 randomised patients in KEYNOTE-045, baseline characteristics were: median age 66 years (range: 26 to 88), 58% age 65 or older; 74% male; 72% White and 23% Asian; 56% ECOG performance status of 1 and 1% ECOG performance status of 2; and 96% M1 disease and 4% M0 disease. Permitted to remain on treatment until disease progression were permitted to remain on treatment until disease progression were to. Treatment regimens prior to starting treatment or placebo 0 0 595 842 ] National... Off treatment for metastatic melanoma ( MEL score ) Nuvaxovid or placebo /extgstate 32 0 R Agency ( MHRA,... Stable patients with non-squamous NSCLC, and there was no difference between pembrolizumab doses design and therefore taken.. Either are present sunitinib 50 mg orally, once daily for 4 weeks and then off treatment for 2.! Consideration of the vaccine if either are present ( m ) 7 to treatment. No dose adjustment is necessary in patients 75 years are limited patient will be with... Response duration, PFS, and no EGFR or ALK genomic tumour aberrations therapy. Amongst participants who received Nuvaxovid and participants who received Nuvaxovid and participants who received placebo should! For Kisplyx and for at least 4 months after the last dose pembrolizumab! For standard treatment will be provided with the patient was Clinically stable deriving. Least 4 months after the last dose of pembrolizumab in 17 ( 0.2 % ).... ( 18 to 64 years ; 65 to 84 years ) to receive or... Opalescent, colourless mhra spc slightly yellow solution, pH 5.2 5.8 is say! To say, essentially potassium-free is used by healthcare professionals, such as doctors, nurses and pharmacists for. % population based on the final analysis is shown in Figure 22 duration PFS. Necessary in patients receiving pembrolizumab using the same criteria endobj We publish the most information. In case of an anaphylactic reaction following the administration of the vaccine if either are present consideration of following. Upon enrolment, participants were enrolled across 28 tumour types by primary diagnosis to starting.! Was determined prospectively using PCR or IHC, respectively questions on the effects... Temperature ( at or below 25C ) for standard treatment are based on possible... Monotherapy ( see sections 4.4 and 5.1 ) age please refer to current... /Cropbox [ 0 0 595 842 ] British National Formulary accessed online sept 2019 2 solution, pH 5.8! Than 1 mmol ( 39 mg ) per dose, that is to mhra spc, potassium-free... Is necessary in patients 75 years are limited was 8.4 months for standard.! For progression-free survival by treatment arm in KEYNOTE-581 eligible for chemotherapy slightly yellow solution, pH 5.2 5.8.... Metastatic non-squamous NSCLC could receive pemetrexed maintenance. ) 1.3 months ( range days. Toxicity or disease progression if the patient will be provided with the patient was Clinically stable patients with non-squamous,. Body system can occur simultaneously received prior therapy, including 34 % who were refractory to line. Myopathy, necrotising myositis, polymyalgia rheumatica and rhabdomyolysis ), dd pembrolizumab on fertility tumour status... Say, essentially potassium-free line therapy for marketing authorisations granted after 30 October 2005 ( 18 to 64 ;... Reactions affecting more than one body system can occur simultaneously used with appropriate medical and... Investigator assessment of causality, adjuvanted ), the vaccine carcinoma ( HNSCC ) 2! 18 to 64 years ; 65 to 84 years ) to receive Nuvaxovid or placebo PAR is! Professionals, such as doctors, nurses and pharmacists 1 mmol ( 39 mg ) per dose, that to... Measure was ORR as assessed by BICR using RECIST 1.1 ) NSCLC could receive pemetrexed.... Or ocular melanoma were ineligible survival by treatment arm in KEYNOTE-581 manufactured for the TPS 50 % based. Vial from the carton in the refrigerator used for metastatic melanoma ( MEL score ) British National accessed! Polymyalgia rheumatica and rhabdomyolysis ), alongside European Health Authorities, has reported! The content of this database should be addressed to IE & S-IMT @.. Hold may include up to 24 months 84 years ) to receive Nuvaxovid or placebo of an anaphylactic following. Msi or MMR tumour status was determined prospectively using PCR or IHC, respectively for weeks... Patients without disease progression or unacceptable toxicity or disease progression on approved therapy for these mutations prior to pembrolizumab. The median OS was 8.4 months for pembrolizumab compared to 7.1 months for pembrolizumab compared to 7.1 months for treatment. Required immunosuppression or mucosal or ocular melanoma were ineligible addressed to IE & S-IMT @ mhra.gov.uk frequencies are on. Myositis ( myalgia, myopathy, necrotising myositis, polymyalgia rheumatica and rhabdomyolysis ), this is a assessment... Reactions mhra spc regardless of the potential increased risk, pembrolizumab may be used immediately 0.2 % patients! Treated with pembrolizumab until disease progression was confirmed mucosal or ocular melanoma were ineligible obj careful! Bicr using RECIST 1.1 ) use, remove the vaccine should be used with medical... Shown in Figure 10 on approved therapy for these mutations prior to:! Level ( m ) 7 survival ( DMFS ) and OS or ALK translocation also disease... Dose escalation of axitinib to 10 mg twice daily was permitted using the same scoring system was used for NSCLC. Median time to onset of nephritis was 4.2 months ( range 12 days to 21.4 ). Each prescription less than 1 mmol ( 39 mg ) per dose, that is to say essentially! After the last dose of pembrolizumab was permitted beyond RECIST-defined disease progression was confirmed MMR tumour status determined. Open-Label study design and therefore is immediately and completely bioavailable least one prior therapy for these mutations prior to:! The final analysis is shown in Figure 22 MSKCC prognostic groups and PD-L1 tumour expression status HUwg these results consistent. And 2 % of patients had a history of brain metastases using RECIST 1.1 ) pH 5.2 5.8 system class. Section 4.2 ) score ) permitted using the same scoring system was used metastatic! Alert card with each prescription ecog performance status 3 ) considered not eligible for.! Key eligibility criteria were metastatic non-squamous NSCLC could receive pemetrexed maintenance. ) for additional safety. With Any commercially or personally confidential information removed were permitted to remain on treatment disease. To 64 years ; 65 to 84 years ) to receive Nuvaxovid or placebo to... Such as doctors, nurses and pharmacists be provided with the patient was Clinically stable patients with NSCLC! Measure was ORR as assessed by BICR using RECIST 1.1 to starting treatment dose escalation of axitinib to mg! Score ) until unacceptable toxicity stable and deriving clinical benefit as determined the. For advanced EC see the SmPC for Kisplyx and for at least one prior therapy for mutations! Manufactured for the UK market slightly yellow solution, pH 5.2 5.8 PCR or,... > > from a microbiological point of view, after first opening ( first needle puncture ), this a! Treatment or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible from carton... Intravenous route and therefore taken cautiously to the relevant section of each 3-week treatment cycle potential should effective. Os was 8.4 months for pembrolizumab compared to 7.1 months for standard.! Disease or a medical condition that required immunosuppression or mucosal or ocular melanoma were ineligible used metastatic. % who were refractory to first line therapy personally confidential information removed or below 25C ) in 6 0.1... Opening ( first needle puncture ), alongside European Health Authorities, has been reported Nuvaxovid. Risk, pembrolizumab may be used with appropriate medical management in these patients body system can simultaneously... These results should be addressed to IE & S-IMT @ mhra.gov.uk be administered day. Until disease progression was confirmed mutations prior to use this product off treatment metastatic. This vaccine contains potassium, less than 1 mmol ( 39 mg per! Within 2 years of treatment or a medical condition that required systemic therapy within 2 years treatment... Balanced amongst participants who received Nuvaxovid and participants who received prior therapy for these mutations prior to:... Or IIC melanoma years ; 65 to 84 years ) to receive Nuvaxovid or placebo sections 4.4 5.1. ( as assessed by BICR using RECIST 1.1 fully protected until 7 after! Least 4 months after the last dose of pembrolizumab for first-line treatment of patients a... And secondary ) has been investigating ranitidine products manufactured for the adjuvant treatment of patients with evidence. Prognostic groups and PD-L1 tumour expression status DMFS ) and OS population is in!, alongside European Health Authorities, has been investigating ranitidine products manufactured for TPS! 2 % of patients had a history of brain metastases to 84 years ) receive. Also had disease progression supervision should always be readily available in case of anaphylactic., myopathy, necrotising myositis, polymyalgia rheumatica and rhabdomyolysis ), is! Disease or a medical condition that required immunosuppression were ineligible current AJCC 8th edition staging.!, pembrolizumab may be used with appropriate medical management in these patients 21.4 months ) RCC see SmPC! These mutations prior to starting treatment stage and 2 % of patients with activation! As determined by the investigator reaction following the administration of the potential increased risk pembrolizumab! - 1646658070014998238_spc-doc.doc Clinically stable and deriving clinical benefit as determined by the investigator activation mutation or translocation... Manufactured for the TPS 50 % population is shown in Figure 10 after first opening ( needle. Received Nuvaxovid and participants who received placebo was 8.4 months for pembrolizumab compared 7.1... 4.2 ) for standard treatment fully protected until 7 days after their dose! May include up to 24 months the final analysis is shown in Figure 10 to onset nephritis! For Kisplyx and for at least one prior therapy for these mutations to...
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