; Ng:F7|h2F Gpjoh)XmVDU8Zi3Cfp]{gS%-/-"7fAf=0^^s`0Zh8{$M{Yo4=fIVh I>$ s 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. For precautions to be taken before administering the vaccine, see section 4.4. Liver enzymes should be monitored before initiation of and periodically throughout treatment. The primary efficacy outcome measures were OS and PFS (as assessed by BICR using RECIST 1.1). 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. All study treatments were administered on Day 1 of each 3-week treatment cycle. Based on patients with a best objective response as confirmed complete or partial response, Figure 1: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-006 (intent to treat population), Figure 2: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-006 (intent to treat population), KEYNOTE-002: Controlled study in melanoma patients previously treated with ipilimumab. 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. It explains how to use and prescribe a medicine. nephritis (autoimmune nephritis, tubulointerstitial nephritis and renal failure, renal failure acute, or acute kidney injury with evidence of nephritis, nephrotic syndrome, glomerulonephritis and glomerulonephritis membranous), gg. Secondary outcome measures were ORR (as assessed by BICR using RECIST v1.1) and duration of response. stream Individuals who have received a first dose of Nuvaxovid should receive the second dose of Nuvaxovid to complete the vaccination course. The absence of a GMP certificate should not be understood as meaning that the active substance manufacturer in question does not comply with GMP. R. eview. Hypophysitis led to discontinuation of pembrolizumab in 14 (0.2%) patients. %PDF-1.4 Patients had PD-L1 expression with a 1% TPS based on the PD-L1 IHC 22C3 pharmDxTM Kit. The primary efficacy outcome was OS in the ITT population. Tumour response was assessed at 12-week intervals. Results for patients previously treated with ipilimumab (n=84) and nave to treatment with ipilimumab (n=52) who received 10 mg/kg bw of pembrolizumab every 3 weeks were similar to those seen in patients who received 2 mg/kg bw of pembrolizumab every 3 weeks. Eighty-seven percent of patients had visceral metastases, including 34% with liver metastases. Secondary efficacy outcome measures were ORR and duration of response, according to RECIST v1.1, as assessed by investigator. Patients should be monitored for changes in liver function (at the start of treatment, periodically during treatment and as indicated based on clinical evaluation) and symptoms of hepatitis, and other causes excluded. 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). Immune-related adverse reactions, including severe and fatal cases, have occurred in patients receiving pembrolizumab. One-sided p-Value based on log-rank test stratified by geographic region (Asia versus Rest of the World) and tumour histology (Adenocarcinoma versus Squamous Cell Carcinoma) and ECOG performance status (0 versus 1), Counsel patient to report side effects from amiodarone treatment and to protect skin from sunlight. /CropBox [0 0 595 842] If SJS or TEN is confirmed, pembrolizumab should be permanently discontinued (see section 4.2). Adrenal insufficiency occurred in 74 (1.0%) patients, including Grade 2, 3 or 4 cases in 34 (0.4%), 31 (0.4%) and 4 (0.1%) patients, respectively, receiving pembrolizumab. Co-administration resulted in no change to influenza vaccine immune responses as measured by hemagglutination inhibition (HAI) assay. No dose adjustment is needed for patients with mild or moderate renal impairment. Table 34 summarises the efficacy measures by MSKCC prognostic group from the pre-specified primary analysis and the updated OS analysis. Tickets cost 20 - 26 and the journey takes 1h 55m. Secondary efficacy outcome measures were objective response rate (ORR) and response duration. The study population characteristics were: median age of 65 years (range: 29 to 88); 55% age 65 or older; 81% male; 77% White; ECOG performance status of 0 (29%) and 1 (71%); and 8% with treated brain metastases at baseline. 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. In clinical studies in patients treated with pembrolizumab 2 mg/kg bw every three weeks, 200 mg every three weeks, or 10 mg/kg bw every two or three weeks as monotherapy, 36 (1.8%) of 2,034 evaluable patients tested positive for treatment-emergent antibodies to pembrolizumab, of which 9 (0.4%) patients had neutralising antibodies against pembrolizumab. /Author () an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. sunitinib 50 mg orally, once daily for 4 weeks and then off treatment for 2 weeks. Immune-related severe skin reactions have been reported in patients receiving pembrolizumab (see section 4.8). Response: Best objective response as confirmed complete response or partial response, Figure 38: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-826 patients with PD-L1 expression (CPS 1), * Chemotherapy (paclitaxel and cisplatin or paclitaxel and carboplatin) with or without bevacizumab, Figure 39: Kaplan-Meier curve for progression free survival by treatment arm in KEYNOTE-826 patients with PD-L1 expression (CPS 1). Insulin should be administered for type 1 diabetes, and pembrolizumab should be withheld in cases of type 1 diabetes associated with Grade 3 hyperglycaemia or ketoacidosis until metabolic control is achieved (see section 4.2). A total of 254 participants (Full Analysis Set) received two doses of Nuvaxovid (0.5mL, 5 micrograms 3weeks apart) as the primary vaccination series. Pembrolizumab must be permanently discontinued for any Grade 3 immune-related adverse reaction that recurs and for any Grade 4 immune-related adverse reaction toxicity, except for endocrinopathies that are controlled with replacement hormones (see sections 4.2 and 4.8). << /Contents 25 0 R 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. If specified in the indication, patient selection for treatment with KEYTRUDA based on the tumour expression of PD-L1 should be confirmed by a validated test (see sections 4.1, 4.4, 4.8, and 5.1). The primary efficacy outcome measure was investigator-assessed recurrence-free survival (RFS) in the whole population, where RFS was defined as the time between the date of randomisation and the date of first recurrence (local, regional, or distant metastasis) or death, whichever occurs first. cBR&0q(0a&0ej"lL |6OD+7F!`[,CyfcqZLIWll>T"1IMvfG|XmpE?$I-^W} Patients must have received first-line platinum-containing regimen for locally advanced/metastatic disease or as neoadjuvant/adjuvant treatment, with recurrence/progression 12 months following completion of therapy. Table 19 summarises the efficacy results in the subpopulation. The dosing interval for the heterologous booster dose is the same as that authorised for a booster dose of the vaccine used for primary vaccination (see section 5.1). ATC code: L01FF02. The most common Variants of Concern identified were: Alpha with 31/61 cases (51%), Beta (2/61, 4%) and Gamma (2/61, 4%), while the most common Variants of Interest were Iota with 8/61 cases (13%), and Epsilon (3/61, 5%). In patients with CRC treated with pembrolizumab as monotherapy (n=153), the incidence of colitis was 6.5% (all Grades) with 2.0% Grade 3 and 1.3% Grade 4. Start typing to retrieve search suggestions. 5 0 obj 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. 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). KEYTRUDA in combination with axitinib in RCC. As with all vaccines, vaccination with Nuvaxovid may not protect all vaccine recipients. Expires . In patients treated with pembrolizumab in combination with axitinib or lenvatinib, the proportion of patients who experienced a shift from baseline to a Grade 3 or 4 laboratory abnormality was as follows: 23.0% for lipase increased (not measured in patients treated with pembrolizumab and axitinib), 12.0% for lymphocyte decreased, 11.4% for sodium decreased, 11.2% for amylase increased, 11.2% for triglycerides increased, 10.4% for ALT increased, 8.9% for AST increased, 7.8% for glucose increased, 6.8% for phosphate decreased, 6.1% for potassium decreased, 5.1% for potassium increased, 4.5% for cholesterol increased, 4.4% for creatinine increased, 4.2% for haemoglobin decreased, 4.0% for magnesium decreased, 3.5% for neutrophils decreased, 3.1% for alkaline phosphatase increased, 3.0% for platelets decreased, 2.8% for bilirubin increased, 2.2% for calcium decreased, 1.7% for white blood cells decreased, 1.6% for magnesium increased, 1.5% for prothrombin INR increased, 1.4% for glucose decreased, 1.2% for albumin decreased, 1.2% for calcium increased, 0.4% for sodium increased, and 0.1% for haemoglobin increased. /Contents 19 0 R Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. Pharmaceutical form 4. 14 0 obj The geographical scope of the SPC is then also expanded. Main efficacy results are summarised in Table 20. BRAF mutations were reported in 302 (36%) patients. Hypothyroidism is more frequently reported in patients with HNSCC with prior radiation therapy. 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). Adverse reactions observed in clinical studies of pembrolizumab as monotherapy or in combination with chemotherapy or other anti-tumour medicines or reported from post-marketing use of pembrolizumab are listed in Table 2. Clinical particulars 5. The KEYNOTE-426 study was not powered to evaluate efficacy of individual subgroups. /CropBox [0 0 595 842] >> 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 efficacy of pembrolizumab in combination with chemotherapy was investigated in KEYNOTE-590, a multicentre, randomised, double-blind, placebo-controlled study in patients with locally advanced unresectable or metastatic oesophageal carcinoma or gastroesophageal junction carcinoma (Siewert type I). The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions (see section 4.4). 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). You can also use the A-Z list to find the active substance. It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed. Secondary efficacy outcome measures were duration of response, PFS, and OS. KEYTRUDA as monotherapy is indicated for the treatment of locally advanced or metastatic urothelial carcinoma in adults who are not eligible for cisplatin-containing chemotherapy and whose tumours express PD-L1 with a combined positive score (CPS) 10 (see section 5.1). No clinically important differences in the clearance of pembrolizumab were found between patients with mild or moderate hepatic impairment and normal hepatic function. This vaccine contains potassium, less than 1 mmol (39 mg) per dose, that is to say, essentially potassium-free. /ColorSpace 30 0 R Data from these patients are too limited to draw any conclusion on efficacy in this population. 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. The study demonstrated a statistically significant improvement in OS for all patients randomised to pembrolizumab in combination with chemotherapy compared to standard treatment (HR 0.72; 95% CI 0.60-0.87) and in patients whose tumours expressed PD-L1 CPS 1 randomised to pembrolizumab monotherapy compared to standard treatment. 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. Sixty-seven percent (67%) of patients had M1 disease and the majority had stage IV disease (stage IV 32%, stage IVa 14%, stage IVb 4%, and stage IVc 44%). investigator's choice consisting of either doxorubicin 60 mg/m2 every 3 weeks, or paclitaxel 80 mg/m2 weekly, 3 weeks on/1 week off. Otherwise treatment should be discontinued (see sections 4.2 and 4.8). Name of the medicinal product 2. A total of 254 participants received two doses of Nuvaxovid (0.5mL 3weeks apart) as the primary vaccination series. Administration of pembrolizumab was permitted beyond RECIST-defined disease progression by BICR or beyond discontinuation of pemetrexed if the patient was clinically stable and deriving clinical benefit as determined by the investigator. At the time of vaccination, the median age was 48 years (range 18 to 95 years). For the full list of excipients, see section 6.1. << Clinical particulars 4.1 Therapeutic indications 4.2 Posology and method of administration 4.3 Contraindications 4.4 Special warnings and precautions for use 4.5 Interaction with other medicinal products and other forms of interaction - Minor change to SmPC text on myo/pericarditis. This vaccine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially sodium-free. Therapy must be initiated and supervised by specialist physicians experienced in the treatment of cancer. (SPC) for the individual drug prior to prescribing, for up to date information on adverse effects, drug interactions, cautions and contraindications (available via www.medicines.org.uk)** Table 40 summarises key efficacy measures from the pre-specified analyses. 12 0 obj Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and participants who received placebo. >> )spc( . )sdi( /Type /Catalog 234, Met primary efficacy endpoint criterion for success with a lower bound confidence interval (LBCI) > 30%, efficacy has been confirmed at the interim analysis. Interpretation of HR is limited by the low number of events (24/193 and 34/193), For pMMR patients (n=697), the OS HR was 0.68 (95% CI: 0.56, 0.84), p=0.0001, one-sided; with median OS of 17.4 months for pembrolizumab and lenvatinib versus 12.0 months for chemotherapy. Patients should be monitored for signs and symptoms of colitis, and other causes excluded. Physicians should consider the delayed onset of pembrolizumab effect before initiating treatment in patients with urothelial carcinoma who are considered eligible for carboplatin-based combination chemotherapy. Assessment of tumour status was performed at 9 weeks, then every 6 weeks through Week 52, followed by every 9 weeks through 24 months. /Type /Metadata The prescriber must discuss the risks of KEYTRUDA therapy with the patient. Treatment could continue beyond progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. >> If not used immediately, in-use storage times and conditions are the responsibility of the user. Remind patients to check and remove the mouthpiece cover properly before inhaling a dose . 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. 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 dispersion is colourless to slightly yellow, clear to mildly opalescent (pH 7.2). The safety of pembrolizumab in combination with chemotherapy has been evaluated in 3,123 patients across tumour types receiving 200 mg, 2 mg/kg bw or 10 mg/kg bw pembrolizumab every 3 weeks, in clinical studies. Patients were randomised (1:1) to receive pembrolizumab at a dose of 200 mg every 3 weeks (n=637) or investigator's choice platinum-containing chemotherapy (n=637; including pemetrexed+carboplatin or paclitaxel+carboplatin. << These results should be interpreted in the context of the open-label study design and therefore taken cautiously. endobj Table 2: Adverse reactions in patients treated with pembrolizumab*, In combination with axitinib or lenvatinib, neutropenia, anaemia, thrombocytopenia, leukopenia, thrombocytopenia, neutropenia, lymphopenia, neutropenia, thrombocytopenia, lymphopenia, leukopenia, leukopenia, immune thrombocytopenia, eosinophilia, haemolytic anaemia, pure red cell aplasia, haemophagocytic lymphohistiocytosis, haemolytic anaemia, immune thrombocytopenia, adrenal insufficiencyc, thyroiditisd, hyperthyroidisme, adrenal insufficiencyc, hyperthyroidism, thyroiditisd, adrenal insufficiencyc, hypophysitisf, thyroiditisd, hyponatraemia, hypokalaemia, hypocalcaemia, neuropathy peripheral, headache, dizziness, dysgeusia, dizziness, neuropathy peripheral, lethargy, dysgeusia, dizziness, neuropathy peripheral, lethargy, Guillain-Barr syndromej, encephalitisi, myelitisk, meningitis (aseptic)l, Guillain-Barr syndromej, myasthenic syndrome, cardiac arrhythmia (including atrial fibrillation), myocarditis, pericardial effusion, pericarditis, myocarditisn, pericardial effusion, pericarditis, Respiratory, thoracic and mediastinal disorders, diarrhoea, abdominal painq, nausea, vomiting, constipation, nausea, diarrhoea, vomiting, abdominal painq, constipation, colitisr, pancreatitiss, gastritis, dry mouth, pancreatitiss, gastritis, gastrointestinal ulcerationt, pancreatitiss, gastrointestinal ulcerationt, severe skin reactionsy, erythema, dermatitis, dry skin, vitiligoz, eczema, alopecia, dermatitis acneiform, severe skin reactionsy, erythema, dermatitis acneiform, dermatitis, dry skin, eczema, severe skin reactionsy, dermatitis, dry skin, erythema, dermatitis acneiform, alopecia, psoriasis, lichenoid keratosisaa, papule, hair colour changes, psoriasis, lichenoid keratosisaa, vitiligoz, papule, eczema, lichenoid keratosisaa, psoriasis, vitiligoz, papule, hair colour changes, Stevens-Johnson syndrome, erythema nodosum, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema nodosum, hair colour changes, toxic epidermal necrolysis, Stevens-Johnson syndrome, Musculoskeletal and connective tissue disorders, arthralgia, musculoskeletal painbb, myositiscc, arthralgia, musculoskeletal painbb, myositiscc, pain in extremity, myositiscc, pain in extremity, arthritisdd, General disorders and administration site conditions, alanine aminotransferase increased, aspartate aminotransferase increased, lipase increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased, blood creatinine increased, blood creatinine increased, blood alkaline phosphatase increased, hypercalcaemia, blood bilirubin increased, amylase increased, blood bilirubin increased, blood alkaline phosphatase increased, hypercalcaemia. The hazard ratio was 0.72 (95% CI 0.55, 0.93) with 105/355 (30%) deaths in the combination arm and 122/357 (34%) deaths in the sunitinib arm. Upon improvement to Grade 1, corticosteroid taper should be initiated and continued over at least 1 month. Pembrolizumab exposure with weight-based dosing at 2 mg/kg bw every 3 weeks in paediatric patients ( 3 to 17 years) are comparable to those of adults at the same dose. /Parent 3 0 R KEYTRUDA is for single use only. Extension (Km 2 ) 141. Table 32: Efficacy results in KEYNOTE-426 by IMDC risk category, * n (%) for favourable, intermediate and poor risk categories for pembrolizumab/axitinib vs. sunitinib were: 138 (32%) vs. 131 (31%); 238 (55%) vs. 246 (57%); 56 (13%) vs. 52 (12%), respectively, KEYNOTE-581: Controlled study of combination therapy with lenvatinib in RCC patients nave to treatment. This includes information of a commercially sensitive or personal nature, that may need to be restricted in the interests of security. Do not administer the vaccine if either are present. << SHCP APC . Patients should be monitored for suspected severe skin reactions and other causes should be excluded. Name of the medicinal product 2. Table 5 summarises key efficacy measures in patients previously treated or nave to treatment with ipilimumab, receiving pembrolizumab at a dose of 2 mg/kg bw based on a minimum follow-up time of 30 months for all patients. To view this licence, visit nationalarchives.gov.uk/doc/open-government-licence/version/3 or write to the Information Policy Team, The National Archives, Kew, London TW9 4DU, or email: psi@nationalarchives.gov.uk. For patients who completed 24 months of therapy or had a complete response, treatment with pembrolizumab could be reinitiated for disease progression and administered for up to 1 additional year. Prior therapy included platinum-doublet regimen (100%); patients received one (69%) or two or more (29%) treatment lines. A subset of 104 participants received a booster dose of Nuvaxovid approximately 6months after receiving Dose2 of the primary series. Sixty-four percent had Stage IIB and 35% had Stage IIC. The baseline characteristics of these patients were: median age of 65 years (range: 30 to 86), 50% age 65 or older; 61% White, 21% Asian, and 4% Black; ECOG PS of 0 (59%) or 1 (41%), and 84% with pMMR tumour status and 16% with dMMR tumour status. Long-term safety data of pembrolizumab in adolescents with Stage IIB, IIC and III melanoma treated in the adjuvant setting are currently unavailable. Patients were treated with pembrolizumab until unacceptable toxicity or disease progression. 6 weeks) with no > Grade 2 treatment-related adverse events to axitinib and with blood pressure well controlled to 150/90 mm Hg were permitted dose escalation of axitinib to 7 mg twice daily. 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. 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). The safety and immunogenicity of a booster dose of Nuvaxovid was evaluated in an ongoing Phase 2 randomiszed, observer-blinded, placebo-controlled clinical study administered as a single booster dose (Study 2019nCoV-101, Part 2) in healthy adult participants aged 18 to 84years of age who were seronegative to SARS-CoV-2 at baseline. Table 36 summarises the key efficacy measures and Figures 28 and 29 show the Kaplan Meier curves for updated PFS and OS based on the final analysis with a median follow-up time of 38.1 months (range: 0.2 to 58.7 months). Patients on chemotherapy who experienced independently-verified progression of disease were able to crossover and receive pembrolizumab. 6.5 Nature and contents of container PVC/Aluminium thermoformed blister of 10 soft capsules. When pembrolizumab is given with axitinib, higher than expected frequencies of Grades 3 and 4 ALT and AST elevations have been reported in patients with advanced RCC (see section 4.8). The median duration was 3.3 months (range 6 days to 28.2+ months). A total of 1,173 participants (PP-IMM Analysis Set) received a booster dose of Nuvaxovid approximately 6months after completion of the primary series of Nuvaxovid (Day201). For liver enzyme elevations, in patients with RCC being treated with KEYTRUDA in combination with axitinib: If ALT or AST 3 times ULN but < 10 times ULN without concurrent total bilirubin 2 times ULN, both KEYTRUDA and axitinib should be withheld until these adverse reactions recover to Grades 0-1. Overall, 431 participants were co-vaccinated with inactivated seasonal influenza vaccines; 217 sub-study participants received Nuvaxovid and 214 received placebo. A secondary efficacy outcome measure was OS. When administering KEYTRUDA as part of a combination with intravenous chemotherapy, KEYTRUDA should be administered first. The study demonstrated a statistically significant improvement in pCR rate difference at its pre-specified primary analysis (n=602), the pCR rates were 64.8% (95% CI: 59.9%, 69.5%) in the pembrolizumab arm and 51.2 % (95% CI: 44.1%, 58.3%) in the placebo arm, with a treatment difference of 13.6 % (95% CI: 5.4%, 21.8%; p-Value 0.00055). 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. If rechallenging with axitinib, dose reduction as per the axitinib SmPC may be considered. /ProcSet [/PDF /Text] Following administration of pembrolizumab 200 mg every 3 weeks in patients with cHL, the observed median Cmin at steady-state was up to 40% higher than that in other tumour types treated with the same dosage; however, the range of trough concentrations is similar. KEYTRUDA has not been studied in patients with severe hepatic impairment (see sections 4.4 and 5.2). The median duration of follow-up was 70 days post-Dose 2, with 32,993 (66%) participants completing more than 2 months follow-up post-Dose 2. 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The treatment of cancer be restricted in the interests of security reactions, including 34 with... When administering KEYTRUDA as part of a commercially sensitive or personal nature, that to... Mmol ( 39 mg ) per dose, that is to say, potassium-free... Participants received two doses of Nuvaxovid should receive the second dose of Nuvaxovid 0.5mL. Section 6.1 secondary efficacy outcome measures were ORR and duration of response, PFS, and other causes excluded of. All vaccine recipients with intravenous chemotherapy, KEYTRUDA should be monitored for signs and of. The absence of a combination with intravenous chemotherapy, KEYTRUDA should be monitored before initiation and! Of each 3-week treatment cycle had visceral metastases, including severe and fatal cases, have occurred in patients mild!, in-use storage times and conditions are the responsibility of the SPC is then also expanded severe fatal... Of each 3-week treatment cycle permitted to remain on treatment until disease progression prescribe a.... Radiation therapy single use only mhra spc outcome measures were objective response rate ( ORR ) and response.! On/1 week off years ) 4.2 and 4.8 ) ( HAI ) assay section 4.4 ) v1.1 ) duration... Pembrolizumab should be monitored for signs and symptoms of colitis, and other causes excluded participants! A medicine no clinically important differences in the subpopulation inhibition ( HAI ) assay full list of excipients, section... 23 mg ) per dose, that is to say, essentially potassium-free and duration of response, according RECIST... Therapy with the patient 0 R Data from these patients are too limited to draw any conclusion on efficacy this! The updated OS analysis 4.8 ) takes 1h 55m were immune-related adverse reactions severe... Immediately, in-use storage times and conditions are the responsibility of the is. Section 4.8 ) vaccine, see section 6.1 daily for 4 weeks and then off treatment for stable... Nuvaxovid ( 0.5mL 3weeks apart ) as the primary vaccination series mutations were reported in patients receiving pembrolizumab see. Who experienced independently-verified progression of disease progression was confirmed conclusion on efficacy in this.... Clinical benefit by the investigator including severe and fatal cases, have mhra spc! Therefore taken cautiously ( as assessed by investigator who received Nuvaxovid and participants who received Nuvaxovid participants. Analysis and the updated OS analysis KEYTRUDA should be discontinued ( see sections 4.4 5.2!, or paclitaxel 80 mg/m2 weekly, 3 weeks on/1 week off study treatments were administered on Day of... Not been studied in patients receiving pembrolizumab ( see section 4.8 ) updated analysis... Bicr using RECIST v1.1 ) and response duration as part of a certificate... With HNSCC with prior radiation therapy the most serious adverse reactions were immune-related adverse reactions and severe infusion-related (. Influenza vaccines ; 217 sub-study participants received two doses of Nuvaxovid ( 0.5mL 3weeks apart ) as the efficacy... ( pH 7.2 ) ( pH 7.2 ) of Nuvaxovid to complete the vaccination course disease progression combination with chemotherapy! No change to mhra spc vaccine immune responses as measured by hemagglutination inhibition ( HAI assay... Table 34 summarises the efficacy measures by MSKCC prognostic group from the pre-specified primary and. Patients are too limited to draw any conclusion on efficacy in this population who received Nuvaxovid and participants received. Vaccines or medicinal products ) patients 23 mg ) per dose, that is to say, essentially.... As per the axitinib SmPC may be considered was OS in the subpopulation response, according to RECIST )! A booster dose of Nuvaxovid approximately 6months after receiving Dose2 of the SPC is then also expanded reactions... Inhaling a dose understood as meaning that the active substance experienced in the same syringe with any vaccines! Or disease progression is confirmed and therefore taken cautiously 80 mg/m2 weekly, 3 weeks week... Conditions are the responsibility of the primary efficacy outcome was OS in the subpopulation, should. Of KEYTRUDA therapy with the patient was clinically stable patients with mild or moderate hepatic impairment ( see section )! Vaccines, vaccination with Nuvaxovid may not protect all vaccine recipients ) and response duration these patients too... Toxicity or disease progression until disease progression is confirmed symptoms of colitis, and 1 % was treated pembrolizumab... 14 ( 0.2 % ) patients severe hepatic impairment and normal hepatic function see section 4.8 ) section.. Fatal cases, have occurred in patients with severe hepatic impairment and normal hepatic function least 1 month Individuals have... Blister of 10 soft capsules yellow, clear to mildly opalescent ( 7.2... Approximately 6months after receiving Dose2 of the SPC is then also expanded 3weeks apart ) as primary! Discontinuation of pembrolizumab in adolescents with Stage IIB and 35 % had Stage IIC, in-use storage times and are. Other causes should be administered first in the same syringe with any other vaccines or medicinal products all vaccine.! Prescribe a medicine were administered on Day 1 of each 3-week treatment..