Five study subjects were ineligible to ASCT due to reasons other than failure to salvage chemotherapy. Hepatitis resolved in 60 patients. 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. There was no statistically significant difference between pembrolizumab and chemotherapy in the final OS analysis that was not adjusted for the potentially confounding effects of crossover. In patients with NSCLC, pneumonitis occurred in 160 (5.7%), including Grade 2, 3, 4 or 5 cases in 62 (2.2%), 47 (1.7%), 14 (0.5%) and 10 (0.4%), respectively. It is recommended to administer the second dose 3 weeks after the first dose (see section 5.1). Patients treated with pembrolizumab without disease progression could be treated for up to 24 months. The median time to onset of colitis was 4.3 months (range 2 days to 24.3 months). Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryo/fetal development, parturition, or post-natal development (see section 5.3). 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. No dose adjustment is needed for patients with mild or moderate renal impairment. Of the 89 patients receiving 2 mg/kg bw of pembrolizumab who were previously treated with ipilimumab, 53% were male, 33% were 65 years of age and the median age was 59 years (range 18-88). Table 26: Efficacy results for pembrolizumab plus chemotherapy in KEYNOTE-048 with PD-L1 expression (CPS 1), Pembrolizumab + Platinum Chemotherapy + 5-FU, Use within 6 hours after first puncture. A total of 307 patients were enrolled and randomised to pembrolizumab (n=153) or chemotherapy (n=154). The results of a post-hoc exploratory subgroup analysis indicated a trend towards reduced survival benefit of pembrolizumab compared to chemotherapy, during both the first 4 months and throughout the entire duration of treatment, in patients who were never-smokers. specialist and MHRA yellow card scheme. Patients with BRAF V600E mutant melanoma were not required to have received prior BRAF inhibitor therapy. Hypothyroidism led to discontinuation of pembrolizumab in 6 (0.1%) patients. Email Address: Registration No: Nuvaxovid was assessed in individuals 18 years of age and older. 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. Preparation and administration of the infusion. Nuvaxovid has no or negligible influence on the ability to drive and use machines. 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. Based on Kaplan-Meier estimates; includes 84 patients with response of 6 months or longer. Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. Administer the infusion solution intravenously over 30 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 to 5 m in-line or add-on filter. 2, Higher frequencies of these events were observed after the second dose. The potential risk of gastrointestinal perforation should be taken into consideration. Some information may have been excluded from public view. Patients were randomised (2:1) to receive either pembrolizumab or placebo via intravenous infusion: o Four cycles of neoadjuvant pembrolizumab 200 mg every 3 weeks or placebo on Day 1 of cycles 1-4 of treatment regimen in combination with: AUC 5 mg/mL/min every 3 weeks on Day 1 of cycles 1-4 of treatment regimen or AUC 1.5 mg/mL/min every week on Day 1, 8, and 15 of cycles 1-4 of treatment regimen and, Paclitaxel 80 mg/m2 every week on Day 1, 8, and 15 of cycles 1-4 of treatment regimen. Consistent with a limited extravascular distribution, the volume of distribution of pembrolizumab at steady-state is small (~6.0 L; CV: 20%). A total of 254 participants (Full Analysis Set) received two doses of Nuvaxovid (0.5mL, 5 micrograms 3weeks apart) as the primary vaccination series. A subgroup analysis was performed as part of the final analysis of KEYNOTE-002 in patients who were BRAF wild type (n=414; 77%) or BRAF mutant with prior BRAF treatment (n=126; 23%) as summarised in Table 6. In patients with EC, Grades 3-5 adverse reactions were 89% for pembrolizumab in combination with lenvatinib and 73% for chemotherapy alone. Physicians should consider the delayed onset of pembrolizumab effect before initiating treatment in patients with poorer prognostic features and/or aggressive disease. Enrolment of adolescents completed in June 2021. FOLFIRI (irinotecan, leucovorin, and FU) or FOLFIRI in combination with either bevacizumab or cetuximab: Irinotecan 180 mg/m2, leucovorin 400 mg/m2 (or levoleucovorin 200 mg/m2), and FU 400 mg/m2 bolus on Day 1, then FU 2,400 mg/m2 over 46-48 hours. At the earlier pre-specified final analysis of ORR (median follow-up time of 17.3 months), statistically significant superiority was achieved for ORR comparing pembrolizumab plus lenvatinib with sunitinib, (odds ratio: 3.84 [95% CI: 2.81, 5.26], p-Value< 0.0001). Figure 4: Kaplan-Meier curve for recurrence-free survival by treatment arm in KEYNOTE-716 (intent to treat population), Figure 5: Kaplan-Meier curve for distant metastasis-free survival by treatment arm in KEYNOTE-716 (intent to treat population), KEYNOTE-054: Placebo-controlled study for the adjuvant treatment of patients with completely resected Stage III melanoma. The primary efficacy outcome measure was ORR as assessed by BICR using RECIST 1.1. Seventy-four percent of patients had received ASCT, 26% were transplant ineligible, and 45% of patients had prior radiation therapy. From a microbiological point of view, the product, once diluted, should be used immediately. Table 14 summarises key efficacy measures and Figures 11 and 12 show the Kaplan-Meier curves for OS and PFS based on the final analysis with a median follow-up of 18.8 months. Exposure to pembrolizumab as expressed by peak concentration (Cmax) or area under the plasma concentration time curve (AUC) increased dose proportionally within the dose range for efficacy. Supply of this product will be subject to the same requirements in Great Britain and Northern Ireland. All patients had M1 disease. In KEYNOTE-051, 161 paediatric patients (62 children aged 9 months to less than 12 years and 99 adolescents aged 12 years to 17 years) with advanced melanoma or PD-L1 positive advanced, relapsed, or refractory solid tumours or lymphoma were administered pembrolizumab 2 mg/kg bw every 3 weeks. If SJS or TEN is confirmed, pembrolizumab should be permanently discontinued (see section 4.2). 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 . 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). Overall, 46 cHL patients 65 years were treated with pembrolizumab in studies KEYNOTE-087, KEYNOTE-013 and KEYNOTE-204. 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. Great Britain. 701927. 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. The high risk category included: pT4, any Grade N0 and M0; any pT, any Grade with nodal involvement and M0. Thyroid disorders, including hypothyroidism, hyperthyroidism and thyroiditis, have been reported in patients receiving pembrolizumab and can occur at any time during treatment. Thirty-one percent had an ECOG Performance Status of 1, 69% had ECOG Performance Status of 0 and 32% had elevated LDH. Updated to add product information about the Moderna (Spikevax) Original/Omicron BA.4/5 vaccine. Figure 26: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-581. Pembrolizumab should be withheld or discontinued for Grades 3 or 4 adrenal insufficiency or symptomatic hypophysitis. The baseline characteristics of these 129 patients included: median age 62 years (40% age 65 or older); 81% male; 78% White, 11% Asian, and 2% Black; 23% and 77% with an ECOG performance status 0 or 1, respectively; and 19% with HPV positive tumours. Patients randomised to chemotherapy were offered pembrolizumab at the time of disease progression. Adverse reactions known to occur with pembrolizumab or combination therapy components given alone may occur during treatment with these medicinal products in combination, even if these reactions were not reported in clinical studies with combination therapy. 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. Chemical and physical in-use stability has been demonstrated for 6 hours at 2C to 25C from the time of first needle puncture to administration. 11 0 obj No case of overdose has been reported. Hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids. This includes information of a commercially sensitive or personal nature, that may need to be restricted in the interests of security. Of the patients randomised to the chemotherapy arm, 55% crossed over and subsequently received treatment with pembrolizumab. Nuvaxovid may also be given as a booster dose in individuals 18 years of age and older following a primary series comprised of an mRNA vaccine or adenoviral vector vaccine (heterologous booster dose). The safety of re-initiating pembrolizumab therapy in patients previously experiencing immune-related myocarditis is not known. 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). This page includes guidance for pharmaceutical companies and regulators on how to prepare and review summaries of product characteristics (SmPCs) for human medicines. The median duration was 1.9 months (range 1 day to 47.1+ months). This does not replace the SPC, which should be read in conjunction with it Date Prepared: October 2011 Reviewed: August 2019 Review Date: July 2022 (Extended to January 2023) References 1. Sevilla. The safety and efficacy of Nuvaxovid in children aged less than 12 years have not yet been established. Unopened vaccine should be stored at 2C to 8C and kept within the outer carton to protect from light. Of these patients, 55% had no recurrence of ALT > 3 times ULN, and of those patients with recurrence of ALT > 3 times ULN, all recovered. Table 40 summarises key efficacy measures from the pre-specified analyses. 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. In patients with HNSCC treated with pembrolizumab as monotherapy (n=909), the incidence of hypothyroidism was 16.1% (all Grades) with 0.3% Grade 3. Bevacizumab 5 mg/kg bw on Day 1 or cetuximab 400 mg/m2 on first infusion, then 250 mg/m2 weekly. Patients were treated with pembrolizumab until unacceptable toxicity or disease progression. KEYTRUDA is for single use only. Cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving pembrolizumab (see section 4.8). KEYTRUDA, as monotherapy or as combination therapy, should be permanently discontinued for Grade 4 or recurrent Grade 3 immune-related adverse reactions, unless otherwise specified in Table 1. As expected for an antibody, pembrolizumab does not bind to plasma proteins in a specific manner. HWK[%'HNR*3'9!0\BZ_~ @HR`_w?|Qw2jw3&R^E Patients were randomised (1:1) to one of the following treatment arms: Pembrolizumab 200 mg on Day 1 of each three-week cycle in combination with cisplatin 80 mg/m2 IV on Day 1 of each three-week cycle for up to six cycles and 5-FU 800 mg/m2 IV per day on Day 1 to Day 5 of each three-week cycle, or per local standard for 5-FU administration. This updated OS analysis was not adjusted to account for subsequent therapies. 09 / 22. 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