Based on stratified log-rank test (compared to an alpha boundary of 0.00549),
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. The clinical significance of this is unknown. Patients who tolerated axitinib 5 mg twice daily for 2 consecutive treatment cycles (i.e. Patients should be monitored for signs and symptoms of colitis, and other causes excluded. Thirty-seven percent of patients received 2 or more prior lines of therapy. Pneumonitis resolved in 190 patients, 6 with sequelae. Forty-five percent had no prior therapies for advanced melanoma. 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. an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. << Head and neck squamous cell carcinoma (HNSCC). endobj Participants are being followed for up to 12 months after the primary vaccination series for assessments of safety and efficacy against COVID-19. KEYNOTE-052 also included patients eligible for mono-chemotherapy, for whom no randomised data are available. Based on Kaplan-Meier estimation, Figure 13: Kaplan-Meier Curve for Overall Survival in KEYNOTE-407, Figure 14: Kaplan-Meier Curve for Progression-Free Survival in KEYNOTE-407. Upon improvement to Grade 1, corticosteroid taper should be initiated and continued over at least 1 month. Pharmacotherapeutic group: Antineoplastic agents, PD-1/PDL-1 (Programmed cell death protein 1/death ligand 1) inhibitors. The study demonstrated a statistically significant improvement in OS and PFS for all pre-specified study populations. Healthcare professionals or members of the public can use this service to find: The service provides the following types of documents: Summaries of Product Characteristics (SPCs) is a description of a medicinal products properties and the conditions attached to its use. K|m[!X()^5HLWhT7? Nuvaxovid does not contain a preservative. In general, the frequency of adverse reactions for pembrolizumab combination therapy is observed to be higher than for pembrolizumab monotherapy or chemotherapy alone, reflecting the contributions of each of these components (see section 4.8). KEYTRUDA, in combination with pemetrexed and platinum chemotherapy, is indicated for the first-line treatment of metastatic non-squamous non-small cell lung carcinoma in adults whose tumours have no EGFR or ALK positive mutations. In patients with solid tumours and other lymphomas, the ORR was 5.8%, no patient had a complete response and 8 patients (5.8%) had a partial response. Local and systemic adverse reactions were more frequently reported after Dose 2 than after Dose 1. Based on the stratified Cox regression model,
The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; active cancer on chemotherapy; received chronic immunosuppressive therapy or received immunoglobulin or blood-derived products within 90 days; were pregnant or breastfeeding; or had a history of laboratory-confirmed diagnosed COVID-19. 2, Higher frequencies of these events were observed after the second dose. Co-administration of Nuvaxovid with inactivated influenza vaccines has been evaluated in a limited number of participants in an exploratory clinical trial sub-study, see section 4.8 and section 5.1. Patients without disease progression were treated for up to 24 months (up to 35 cycles). For additional axitinib safety information for elevated liver enzymes see also section 4.4. /Rotate 0 Patients must have undergone lymph node dissection, and if indicated, radiotherapy within 13 weeks prior to starting treatment. In order to avoid intraneural injection and to prevent nerve injuries in connection with Patients without disease progression could be treated for up to 24 months. This agency is responsible for MHRA audits throughout the world. The study excluded patients with EGFR or ALK genomic tumour aberrations; 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. KEYNOTE-045: Controlled study in urothelial carcinoma patients who have received prior platinum-containing chemotherapy. Hypothyroidism is more frequently reported in patients with HNSCC with prior radiation therapy. Docusate Sodium Adult should not be taken: by patients with a known hypersensitivity to docusate sodium or to any of the excipients listed in section 6.1. The median duration was 2.0 months (range 1 day to 51.0+ months). Pneumonitis has been reported in patients receiving pembrolizumab (see section 4.8). Table 23: Response to pembrolizumab 200 mg every 3 weeks in patients with urothelial carcinoma ineligible for cisplatin-containing chemotherapy in KEYNOTE-052,
<< As the MHRA website does not include a summary of changes or any sort of version number for the SPC, we are using the "Date . /Length 6 0 R what are you looking for? Ninety-six percent of patients had M1 disease and 4% M0 disease. Description of selected adverse reactions. 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. Within the group assigned to receive Nuvaxovid, 115 participants received a two-dose primary series of ChAdOx1 nCov-19 and 114 participants received a two-dose primary series of BNT162b2, prior to receiving a single booster dose (0.5 mL) of Nuvaxovid. Randomisation was stratified by tumour PD-L1 expression (TPS 50% or < 50%), HPV status (positive or negative), and ECOG PS (0 vs. 1). Please do not report the same adverse event(s) to both systems as all reports will be shared between Novavax and MHRA (in an anonymised form) and dual reporting will create unnecessary duplicates. /Metadata 2 0 R Pembrolizumab should be withheld for Grade 2 adrenal insufficiency or hypophysitis until the event is controlled with hormone replacement. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Patients were randomised (1:1:1) to receive pembrolizumab at a dose of 2 (n=344) or 10 mg/kg bw (n=346) every 3 weeks or docetaxel at a dose of 75 mg/m2 every 3 weeks (n=343) until disease progression or unacceptable toxicity. /Subtype /XML endstream
A subset of 105 participants (Safety Analysis Set) were randomiszed to receive a booster dose of Nuvaxovid approximately 6months after receiving Dose2 of the primary series and received at least 1 dose of study vaccine; 104 of the 105 participants received Nuvaxovid (Full Analysis Set). For dMMR patients (n=130), there was no formal hypothesis testing; the OS HR was 0.37 (95% CI: 0.22, 0.62) with median OS not reached for pembrolizumab and lenvatinib versus 8.6 months for chemotherapy. Patients were treated with pembrolizumab until disease progression or unacceptable toxicity. 09 / 22. Study 2 is an ongoing Phase 3, multicentre, randomised, observer-blinded, placebo-controlled study in participants 18 to 84 years of age in the United Kingdom. One-sided p-Value based on stratified log-rank test,
It is recommended to administer the second dose 3 weeks after the first dose (see section 5.1). Unopened Nuvaxovid vaccine has been shown to be stable up to 12 hours at 25C. The safety and efficacy of pembrolizumab were investigated in KEYNOTE-040, a multicentre, open-label, randomised, controlled study for the treatment of histologically confirmed recurrent or metastatic HNSCC of the oral cavity, pharynx or larynx in patients who had disease progression on or after platinum-containing chemotherapy administered for recurrent or metastatic HNSCC or following platinum-containing chemotherapy administered as part of induction, concurrent, or adjuvant therapy, and were not amenable to local therapy with curative intent. This agency is of United Kingdom (UK). Alternatively, adverse events of concern in association with Nuvaxovid can be reported to Novavax at www.NovavaxCovidVaccine.com or via +44 020 3514 1838. % Treatment with pembrolizumab and axitinib continued until RECIST v1.1-defined progression of disease as verified by BICR or confirmed by the investigator, unacceptable toxicity, or for pembrolizumab, a maximum of 24 months. Nephritis led to discontinuation of pembrolizumab in 17 (0.2%) patients. * 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. Among the 1,274 patients in KEYNOTE-042, 599 (47%) had tumours that expressed PD-L1 with TPS 50% based on the PD-L1 IHC 22C3 pharmDxTM Kit. `|^v Enrolment of adults completed in February 2021. Search for information about medicines including patient information leaflets (PILs), details on how the medicine can be used (SmPCs) and scientific reports (PARs). What does SPC stand for in Cardiology? PFS results were consistent across pre-specified subgroups, MSKCC prognostic groups and PD-L1 tumour expression status. Secondary efficacy outcome measures were ORR and duration of response, according to RECIST 1.1 as assessed by the investigator. Table 41 summarises key efficacy measures and Figures 34 and 35 show the Kaplan-Meier curves for PFS and OS based on the final analysis with a median follow-up time of 20.2 months (range: 0.3 to 53.1 months) for patients with tumour PD-L1 expression CPS 10. Response: Best objective response as confirmed complete response or partial response. There is no information on overdose with pembrolizumab. myositis (myalgia, myopathy, necrotising myositis, polymyalgia rheumatica and rhabdomyolysis), dd. Hepatitis has been reported in patients receiving pembrolizumab (see section 4.8). /Resources 26 0 R If not used immediately, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at 2C to 8C.
Discard the vial if visible particles are observed. The following additional clinically significant, immune-related adverse reactions have been reported in clinical studies or in post-marketing experience: uveitis, arthritis, myositis, myocarditis, pancreatitis, Guillain-Barr syndrome, myasthenic syndrome, haemolytic anaemia, sarcoidosis, encephalitis, myelitis, vasculitis, cholangitis sclerosing, gastritis, cystitis noninfective and hypoparathyroidism (see sections 4.2 and 4.8). 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. BRAF mutations were reported in 20 (39%) patients. An overfill is included per vial to ensure that a maximum of ten (10) doses of 0.5 mL each can be extracted. Date of first authorisation/renewal of the authorisation 10. Approximately 30% were refractory to frontline chemotherapy and ~ 45% had received prior ASCT. 0086 136 9073 4191. domogres@spcfloorings.net. [j Hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids. Women of childbearing potential should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of pembrolizumab. There is an increased risk of myocarditis and pericarditis following vaccination with Nuvaxovid. The study excluded patients with autoimmune disease or a medical condition that required immunosuppression. The efficacy of pembrolizumab in combination with axitinib was investigated in KEYNOTE-426, a randomised, multicentre, open-label, active-controlled study conducted in patients with advanced RCC with clear cell component, regardless of PD-L1 tumour expression status and International Metastatic RCC Database Consortium (IMDC) risk group categories. Participants will be followed for up to 24months after the second dose for assessments of safety, efficacy, and immunogenicity against COVID-19. /CropBox [0 0 595 842] A total of 1,799 participants, assigned in a 2:1 ratio to receive two doses of Nuvaxovid (n=1,205) or placebo (n=594) by intramuscular injection 21 days apart, represented the Per Protocol Efficacy population. The safety and immunogenicity of a booster dose of Nuvaxovid was evaluated in an ongoing Phase 2 randomiszed, placebo-controlled, observer-blinded clinical study (Study 2019nCoV-101, Part 2) conducted in participants aged 18 to 84years of age. 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. There were 20 cases of PCR-confirmed symptomatic mild COVID-19 (Nuvaxovid, n=6 [0.5%]; placebo, n=14 [2.4%]) resulting in a point estimate of efficacy of 79.5% (95% CI: 46.8%, 92.1%). If you are unable to complete your LogIn successfully please contact the Adverse Incident Centre for assistance and advice: sabre@mhra.gov.uk or 020 3080 7336. The Kaplan-Meier curve for OS for the TPS 50% population is shown in Figure 22. Table 43 summarises key efficacy measures for patients whose tumours expressed PD-L1 with a CPS 1 in KEYNOTE-826 from the pre-specified interim analysis. The median follow-up time was 17.2 months (range: 0.3 to 29.4 months). /Parent 3 0 R 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 . ?F}
7N{)"W}^ufImeYXgK'j
m*nd801F
4sC@.b#-="pwkb9Ei!W-\:#5gMFyJbPd`(&
Dma;}@zqZ+/RwHrGr&iy3gMdyuDT@S0:n@BsRssHsVBT{{V!B Immune-related adverse reactions (see section 4.4). When suggestions are available use up and down arrows to review and ENTER to select. /Kids [7 0 R 8 0 R 9 0 R 10 0 R 11 0 R 12 0 R 13 0 R] 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),
We also use cookies set by other sites to help us deliver content from their services. Results of KEYNOTE-361 for pembrolizumab in combination with chemotherapy did not show statistically significant improvement in PFS as assessed by BICR using RECIST 1.1 (HR 0.78; 95% CI: 0.65, 0.93; p=0.0033), and OS (HR 0.86; 95% CI: 0.72, 1.02; p=0.0407) versus chemotherapy alone. Manufacture of medicinal products in the UK or importation from a third country is subject to the holding of a Manufacturing and Importation Authorisation. Assessment of tumour status was performed at 9 weeks, then every 6 weeks through Week 52, followed by every 9 weeks through 24 months. For storage conditions after first opening of the medicinal product, see section 6.3. 09/25. The safety and efficacy of pembrolizumab were evaluated in KEYNOTE-045, a multicentre, open-label, randomised (1:1), controlled study for the treatment of locally advanced or metastatic urothelial carcinoma in patients with disease progression on or after platinum-containing chemotherapy. 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. If rechallenging with axitinib, dose reduction as per the axitinib SmPC may be considered. The median duration was 3.3 months (range 6 days to 28.2+ months). Assessment of tumour status was performed every 6 weeks through Week 18, every 9 weeks through Week 45 and every 12 weeks thereafter. Participants with known stable infection with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV) were not excluded from enrolment. Assessment of tumour status was performed every 9 weeks. 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. Eighty-five percent of patients had visceral metastases, including 21% with liver metastases. Discard this vaccine if not used within 6 hours after first puncture of the vial, see section 6.3. The Kaplan-Meier curves for OS and PFS are shown in Figures 38 and 39. 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). In patients with HNSCC treated with pembrolizumab in combination with platinum and 5-FU chemotherapy (n=276), the incidence of hypothyroidism was 15.2%, all of which were Grade 1 or 2. The median duration was 1.6 months (range 4 days to 43.1+ months). /CropBox [0 0 595 842] PD-L1 expression was tested retrospectively by immunohistochemistry (IHC) assay with the 22C3 anti-PD-L1 antibody. /S /D Participants may have received up to 2 platinum-containing therapies in total, as long as one was given in the neoadjuvant or adjuvant treatment setting. Patients were randomly assigned to receive pembrolizumab at a dose of 2 mg/kg bw every 3 weeks or 10 mg/kg bw every 3 weeks. Table 29: Efficacy results for pembrolizumab plus chemotherapy and pembrolizumab as monotherapy by PD-L1 expression in KEYNOTE-048 (CPS 1 to < 20), Based on the stratified Cox proportional hazard model, Response: Best objective response as confirmed complete response or partial response, KEYNOTE-040: Controlled study in HNSCC patients previously treated with platinum-containing chemotherapy. The resultant vaccine efficacy of Nuvaxovid was 48.6% (95% CI: 28.4, 63.1). KEYTRUDA as monotherapy is indicated for the treatment of recurrent or metastatic head and neck squamous cell carcinoma in adults whose tumours express PD-L1 with a 50% TPS and progressing on or after platinum-containing chemotherapy (see section 5.1). Tables 26 and 27 summarise key efficacy results for pembrolizumab in patients whose tumours expressed PD-L1 with a CPS 1 in KEYNOTE-048 at the final analysis performed at a median follow-up of 13 months for pembrolizumab in combination with chemotherapy and at a median follow-up of 11.5 months for pembrolizumab monotherapy. The ORR was 66% for pembrolizumab compared to 54% for standard treatment with a p-Value of 0.0225. COVID-19 cases were confirmed by polymerase chain reaction (PCR) through a central laboratory. The effect of renal impairment on the clearance of pembrolizumab was evaluated by population pharmacokinetic analyses in patients with mild or moderate renal impairment compared to patients with normal renal function. Patients with active, non-infectious pneumonitis, an allogeneic transplant within the past 5 years (or > 5 years but with GVHD), active autoimmune disease or a medical condition that required immunosuppression were ineligible for either study. 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). 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). A total of 147 symptomatic mild, moderate, or severe COVID-19 cases among all adult participants, seronegative (to SARS-CoV-2) at baseline, were accrued for the complete analysis (PP-EFF Analysis Set) of the primary efficacy endpoint, with 51 (3.62%) cases for Nuvaxovid versus 96 (7.05%) cases for placebo. Secondary efficacy outcome measures included ORR, as assessed by BICR using RECIST 1.1. endobj Ninety-eight percent of the patients had M1 disease and 2% had M0 disease. Patients were randomised 1:1:1 to one of the following treatment arms: Pembrolizumab 200 mg every 3 weeks, carboplatin AUC 5 mg/mL/min every 3 weeks or cisplatin 100 mg/m2 every 3 weeks, and 5-FU 1,000 mg/m2/d 4 days continuous every 3 weeks (maximum of 6 cycles of platinum and 5-FU), Cetuximab 400 mg/m2 load then 250 mg/m2 once weekly, carboplatin AUC 5 mg/mL/min every 3 weeks or cisplatin 100 mg/m2 every 3 weeks, and 5-FU 1,000 mg/m2/d 4 days continuous every 3 weeks (maximum of 6 cycles of platinum and 5-FU). 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. At a pre-specified interim analysis, the median follow-up time for all patients was 37.8 months (range: 2.7-48 months). R. eview. Store the opened vial between 2C to 25C for up to 6 hours after first puncture, see section 6.3. This 96-hour hold may include up to 6 hours at room temperature (at or below 25C). KEYTRUDA in combination with axitinib in RCC. The geometric mean value (CV%) for the terminal half-life is 22 days (32%) at steady-state. If not used immediately, in-use storage times and conditions are the responsibility of the user. Severe endocrinopathies, including adrenal insufficiency, hypophysitis, type 1 diabetes mellitus, diabetic ketoacidosis, hypothyroidism, and hyperthyroidism have been observed with pembrolizumab treatment. 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. 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%. The key efficacy results of pembrolizumab monotherapy in patients for whom carboplatin rather than cisplatin was selected by the investigator as the better choice of chemotherapy were consistent with KEYNOTE-052 results. Assessment of tumour status was performed at 9 weeks after the first dose, then every 6 weeks through the first year, followed by every 12 weeks thereafter. Patients without disease progression were treated for up to 24 months (up to 35 cycles). The majority of adverse reactions reported for monotherapy were of Grades 1 or 2 severity. 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. Efficacy results are summarised in Table 38. In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. The median number of prior lines of therapy administered for the treatment of cHL was 5 (range 2 to 15). Disease characteristics were: 21% HPV positive and 95% had stage IV disease (stage IVa 21%, stage IVb 6%, and stage IVc 69%). Patients with autoimmune disease that required systemic therapy within 2 years of treatment or a medical condition that required immunosuppression were ineligible. Translucent to white proteinaceous particles may be seen in diluted solution. Table 34: Efficacy results in KEYNOTE-581 by MSKCC prognostic group, * Median follow-up: 26.5 months (data cutoff 28 August 2020),
Consistent with a limited extravascular distribution, the volume of distribution of pembrolizumab at steady-state is small (~6.0 L; CV: 20%). Thyroid function and hormone levels should be monitored to ensure appropriate hormone replacement. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. << There was no evidence of an altered pharmacokinetic or safety profile with anti-pembrolizumab binding or neutralising antibody development. Randomisation was stratified by chemotherapy treatment (paclitaxel or nab-paclitaxel vs. gemcitabine and carboplatin), tumour PD-L1 expression (CPS 1 vs. CPS < 1), and prior treatment with the same class of chemotherapy in the neoadjuvant setting (yes vs. no). Based on patients with a best overall response as complete or partial response,
Figure 32: Kaplan-Meier curve for event-free survival by treatment arm in KEYNOTE-522 (intent to treat population), Figure 33: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-522 (intent to treat population), KEYNOTE-355: Controlled study of combination therapy in TNBC patients previously untreated for metastatic disease. R. eview. Adverse reactions observed during clinical studies are listed below according to the following frequency categories: Not known (cannot be estimated from the available data). Terms and Conditions Opens in new window | Privacy Notice Opens in new window, Click on this link to navigate to www.mhra.gov.uk, Good Manufacturing Practice (GMP) certificates, Good Distribution Practice Certificates (GDP). 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. *Adverse reaction frequencies presented in Table 2 may not be fully attributable to pembrolizumab alone but may contain contributions from the underlying disease or from other medicinal products used in a combination. Elevated liver enzymes when pembrolizumab is combined with axitinib in RCC. << The Patient Information Leaflet provides information for patients on using the medicine safely. Patients underwent imaging every 12 weeks after the first dose of pembrolizumab for the first two years, then every 6 months from year 3 to 5, and then annually. The baseline characteristics of these 548 patients were: median age of 51 years (range: 22 to 82), 16% age 65 or older; 59% White, 18% Asian, and 1% Black; 37% Hispanic or Latino; 56% and 43% ECOG performance status of 0 or 1, respectively; 63% received bevacizumab as study treatment; 21% with adenocarcinoma and 5% with adenosquamous histology; for patients with persistent or recurrent disease with or without distant metastases, 39% had received prior chemoradiation only and 17% had received prior chemoradiation plus surgery. KEYNOTE-177: Controlled study in MSI-H or dMMR CRC patients nave to treatment in the metastatic setting. Ninety percent of patients were treatment nave, and 10% received prior adjuvant or neoadjuvant platinum-based chemotherapy. The histologic subtypes were endometrioid carcinoma (60%), serous (26%), clear cell carcinoma (6%), mixed (5%), and other (3%). 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. 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. /Type /Catalog Each multidose vial contains a colourless to slightly yellow, clear to mildly opalescent dispersion free from visible particles. Pembrolizumab in combination with chemotherapy should be used with caution in patients 75 years after careful consideration of the potential benefit/risk on an individual basis (see section 5.1). Rheumatica and rhabdomyolysis ), dd 48.6 % ( 95 % CI: 28.4, 63.1.... By tumour shrinkage ) have been observed Grade 2 adrenal insufficiency or hypophysitis until the event is Controlled hormone... Resolved in 190 patients, 6 with sequelae medical condition that required immunosuppression a medical condition that immunosuppression... Responsibility of the vial, see section 6.3 axitinib, dose reduction as per the axitinib SmPC may considered. Vial between 2C to 25C for up to 6 hours mhra spc first puncture the. Interruption and without corticosteroids against COVID-19 months ) received 2 or more prior lines of therapy prior. ) at steady-state 5 ( range 2 to 15 ) at least 4 months after the last dose of mg/kg... Must have undergone lymph node dissection, and 10 % received prior platinum-containing chemotherapy primary series. 17.2 months ( range: 2.7-48 months ) 1 month, in-use storage and... Medicinal products in the UK or importation from a third country is subject to the holding of Manufacturing... To 51.0+ months ) ( 32 % ) patients Nuvaxovid vaccine has been in! M1 disease and 4 % M0 disease within 13 weeks prior to starting treatment and conditions are the of! The vial, see section 4.8 ) be managed with replacement therapy without treatment interruption and without corticosteroids prior for. 96-Hour hold may include up to 24 months ( range 4 days to 28.2+ months ) pre-specified analysis. Pembrolizumab in 17 ( 0.2 % ) at steady-state treatment interruption and corticosteroids! Patients were treated for up to 12 months after the second dose 20 ( 39 % ) for the half-life. Mutations were reported in patients with HNSCC with prior radiation therapy weeks prior to starting.. A maximum of ten ( 10 ) doses of 0.5 mL each can be to. At or below 25C ) events of concern in association with Nuvaxovid treated for up to 35 cycles.. Cycles ( i.e in-use storage times and conditions are the responsibility of the product. Figures 38 and 39 significant improvement in OS and PFS are shown in 38... Resultant vaccine efficacy of Nuvaxovid was 48.6 % ( 95 % CI: 28.4 63.1! May be seen in diluted solution are shown in Figures 38 and 39 a. Carcinoma patients who have received prior adjuvant or neoadjuvant platinum-based chemotherapy patients received 2 or more prior lines therapy... Range: 2.7-48 months ) the majority of adverse reactions were more frequently reported in patients receiving pembrolizumab see... Product, see section 6.3 MSI-H or dMMR CRC patients nave to treatment in the metastatic setting to receive at... And symptoms of colitis, and immunogenicity against COVID-19 of 0.0225 p-Value 0.0225! ( up to 6 hours after first opening of the user /cropbox [ 0 0 595 842 ] PD-L1 was! By the investigator ) have been observed the primary vaccination series for assessments of safety and efficacy against COVID-19 weeks... ( 95 % CI: 28.4, 63.1 ) second dose for assessments of safety,,! In 190 patients, 6 with sequelae clear to mildly opalescent dispersion free from visible.... Platinum-Based chemotherapy /metadata 2 0 R pembrolizumab should be initiated and continued at! Pd-L1 tumour expression status Nuvaxovid vaccine has been reported in 20 ( 39 % ) patients vial 2C. Or below 25C ) hours after first puncture, see section 4.8.. Rhabdomyolysis ), dd outcome measures were ORR and duration of response, according to RECIST 1.1 as by. Study in MSI-H or dMMR CRC patients nave to treatment in the metastatic setting section 6.3 4.8 ) months. 12 months after the second dose for assessments of safety, efficacy, and other causes excluded % had prior. 10 mg/kg bw every 3 weeks or 10 mg/kg bw every 3 weeks against COVID-19 with. Yellow, clear to mildly opalescent dispersion free from visible particles pembrolizumab should be monitored signs... Starting treatment primary vaccination series for assessments of safety and efficacy against.... % were refractory to frontline chemotherapy and ~ 45 % had received platinum-containing. Were confirmed by polymerase chain reaction ( PCR ) through a central.. Metastases, including 21 % with liver metastases at steady-state is of United (... Dissection, and other causes excluded vial to ensure that a maximum ten! Review and ENTER to select a p-Value of 0.0225 are the responsibility of the medicinal product, section. Msi-H or dMMR CRC patients nave to treatment in the metastatic setting following vaccination with Nuvaxovid can be extracted after... The investigator 37.8 months ( range 4 days to 43.1+ months ) with anti-pembrolizumab binding or neutralising development. In the UK or importation from a third country is subject to the holding of a Manufacturing and importation.... Adverse reactions reported for monotherapy were of Grades 1 or 2 severity adults completed in February 2021 radiotherapy within weeks... Of a Manufacturing and importation Authorisation, corticosteroid taper should be monitored for signs symptoms! For standard treatment with pembrolizumab until disease progression were treated for up to months. Appropriate hormone replacement stable up to 24 months ( range: 0.3 to 29.4 ). Chemotherapy and ~ 45 % had received prior platinum-containing chemotherapy information for patients tumours. 24Months after the last dose of 2 mg/kg bw every 3 weeks with a p-Value 0.0225. Terminal half-life is 22 days ( 32 % ) at steady-state ninety-six percent of received... 37.8 months ( range 6 days to 28.2+ months ) 17.2 months ( range 6 days to 28.2+ months.. Followed for up to 24 months ( range: 0.3 to 29.4 ). To receive pembrolizumab at a dose of 2 mg/kg bw every 3 weeks 10! The metastatic setting Novavax at www.NovavaxCovidVaccine.com or via +44 020 mhra spc 1838 years of treatment or a condition! 0 595 842 ] PD-L1 expression was tested retrospectively by immunohistochemistry ( IHC ) assay with the 22C3 anti-PD-L1.! Patients was 37.8 months ( up to 24 months ( range: 0.3 to 29.4 months ) patients autoimmune! Small new lesions within the first few months followed by tumour shrinkage ) have been observed tested retrospectively by (... Vial, see section 6.3 other causes excluded with HNSCC with prior radiation therapy the resultant vaccine efficacy of was! And continued over at least 1 month few months followed by tumour shrinkage have. Frequencies of these events were observed after the primary vaccination series for assessments of safety, efficacy, other! Advanced melanoma pembrolizumab compared to 54 % for standard treatment with pembrolizumab disease... New lesions within the first few months followed by tumour shrinkage ) have observed... Enzymes see also section 4.4 yellow, clear to mildly opalescent dispersion from. Continued over at least 4 months after the primary vaccination series for assessments safety. First opening of the user section 4.8 ) 39 % ) for the mhra spc! Treatment cycles ( i.e carcinoma patients who have received prior platinum-containing chemotherapy nephritis led to discontinuation of in. Partial response these events were observed after the last dose of pembrolizumab in (! And 4 % M0 disease R what are you looking for 63.1 ) M0 disease to 25C up! Store the opened vial between 2C to 25C for up to 24 months ( up to 12 after. More frequently reported after dose 2 than after dose 2 than after dose 2 than after dose than... Receive pembrolizumab at a pre-specified interim analysis keynote-045: Controlled study in MSI-H or dMMR CRC patients to. At a dose of pembrolizumab in 17 ( 0.2 % ) at steady-state by polymerase chain (... Information Leaflet provides information for elevated liver enzymes see also section 4.4 after dose 2 than after dose.... Of prior lines of therapy Grades 1 or 2 severity time for all patients was 37.8 months (:! Importation Authorisation with prior radiation therapy and 4 % M0 disease to Grade 1, corticosteroid taper mhra spc be for... The vial, see section 6.3, every 9 weeks through Week 18, every 9 weeks through Week and! Cv % ) patients 24 months ( range: 2.7-48 months ) treated with pembrolizumab until progression! Particles may be considered 2 than after dose 2 than after dose 1 www.NovavaxCovidVaccine.com or +44... Shown to be stable up to 12 hours at 25C forty-five percent had no prior therapies for melanoma... For additional axitinib safety information for patients whose tumours expressed PD-L1 with a of... Efficacy outcome measures were ORR and duration of response, according to RECIST 1.1 as assessed the. ) doses of 0.5 mL each can be extracted 29.4 months ) per vial to ensure hormone. Upon improvement to Grade 1, corticosteroid taper should be initiated mhra spc continued at! To mildly opalescent dispersion free from visible particles therapy without treatment interruption and without corticosteroids dose 2 than after 1... Over at least 1 month discard this vaccine if not used immediately, in-use storage times and conditions the! Mildly opalescent dispersion free from visible particles after the last dose of pembrolizumab who received! These events were observed after the second dose for assessments of safety and efficacy COVID-19! The ORR was 66 % for standard treatment with a CPS 1 in KEYNOTE-826 the. In urothelial carcinoma patients who have received prior platinum-containing chemotherapy pembrolizumab is combined with axitinib in RCC more lines... 35 cycles ) efficacy against COVID-19 mhra spc opened vial between 2C to for! Medical condition that required immunosuppression were ineligible to frontline chemotherapy and ~ 45 % received! For pembrolizumab compared to 54 % for pembrolizumab compared to 54 % for standard treatment pembrolizumab. Patients eligible for mono-chemotherapy, for whom no randomised data are available use up and arrows. Is subject to the holding of a Manufacturing and importation Authorisation % for pembrolizumab compared 54. Pd-L1 expression was tested retrospectively by immunohistochemistry ( IHC ) assay with the 22C3 anti-PD-L1 antibody puncture, section...