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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. 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. Use of pembrolizumab in urothelial carcinoma patients who have received prior platinum-containing chemotherapy. Eighty-two percent had M1c stage, 73% had at least two and 32% of patients had three or more prior systemic therapies for advanced melanoma. There are no data on the use of pembrolizumab in pregnant women. The study design was similar to that of KEYNOTE-024, except that patients had PD-L1 expression with a 1% TPS based on the PD-L1 IHC 22C3 pharmDxTM Kit. Comorbidities included: obesity (body mass index (BMI) 30 kg/m2); chronic lung disease; diabetes mellitus type 2, cardiovascular disease; chronic kidney disease; or human immunodeficiency virus (HIV). 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. Assessment of tumour status was performed at Weeks 8, 16, and 24, then every 9 weeks for the first year, and every 12 weeks thereafter. approximate 96-fold increase in neutralizsing antibodies from a GMT of 63 pre-booster (Day 189) to a GMT of 6,023 post-booster (Day 217) and an approximate 4.1-fold increase from a peak GMT (14 days post-Dose 2) of 1,470. Events of anaphylaxis have been reported with Nuvaxovid vaccines. A prolonged time to deterioration in EORTC QLQ-C30 global health status/QoL was observed for patients treated with pembrolizumab compared to investigator's choice chemotherapy (HR 0.70; 95% CI 0.55-0.90). KEYNOTE-006: Controlled study in melanoma patients nave to treatment with ipilimumab. Dont include personal or financial information like your National Insurance number or credit card details. Nuvaxovid is for intramuscular injection only, preferably into the deltoid muscle of the upper arm. 09/24. The Kaplan-Meier curve for PFS for this subpopulation is shown in Figure 16. 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). 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. Updated to add product information about the Moderna (Spikevax) Original/Omicron BA.4/5 vaccine. Animal reproduction studies have not been conducted with pembrolizumab; however, in murine models of pregnancy blockade of PD-L1 signalling has been shown to disrupt tolerance to the foetus and to result in an increased foetal loss (see section 5.3). ?%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! Clear to slightly opalescent, colourless to slightly yellow solution, pH 5.2 5.8. In the Hodgkin lymphoma population (n=22), in patients aged 11 years to 17 years, the baseline characteristics were median age 15 years; 64% male; 68% White; 77% had a Lansky/Karnofsky scale 90-100 and 23% had scale 70-80. The study demonstrated a statistically significant improvement in OS and PFS for all pre-specified study populations. Of the 161 patients, 137 were enrolled with solid tumours, 22 with Hodgkin lymphoma, and 2 with other lymphomas. For suspected immune-related adverse reactions, adequate evaluation to confirm aetiology or exclude other causes should be ensured. This. Pharmacological properties 6. When reporting, please include the vaccine brand and batch/lot number, if available. Patients should be monitored for signs and symptoms of pneumonitis. The most frequent adverse reactions were injection site tenderness (71%), injection site pain (67%), headache (63%), myalgia (57%), fatigue (54%), malaise (43%), nausea or vomiting (23%), arthralgia (19%) and pyrexia (17%). One patient experienced engraftment syndrome post-transplant. For use in combination, see the Summary of Product Characteristics (SmPC) for the concomitant therapies. 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. 2022 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. 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. Adverse reactions were usually mild to moderate in severity with a median duration of less than or equal to 2 days for local events and less than or equal to 1 day for systemic events following vaccination. endobj Based on the stratified Cox regression model,
All prescribers of KEYTRUDA must be familiar with the Physician Information and Management Guidelines. The efficacy of Nuvaxovid may be lower in immunosuppressed individuals. # From product-limit (Kaplan-Meier) method for censored data, Figure 34: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-355 patients with PD-L1 expression (CPS 10), Figure 35: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-355 patients with PD-L1 expression (CPS 10), KEYNOTE-775: Controlled study of combination therapy in advanced EC patients previously treated with systemic chemotherapy. Based on the severity of the adverse reaction, pembrolizumab should be withheld for Grade 3 skin reactions until recovery to Grade 1 or permanently discontinued for Grade 4 skin reactions, and corticosteroids should be administered (see section 4.2). Lenvatinib should be withheld, dose reduced, or discontinued in accordance with the instructions in the lenvatinib SmPC for combination with pembrolizumab. Immune-related adverse reactions affecting more than one body system can occur simultaneously. /Title (Microsoft Word - 1646658070014998238_spc-doc.doc) The effect of hepatic impairment on the clearance of pembrolizumab was evaluated by population pharmacokinetic analyses in patients with mild and moderate hepatic impairment (as defined using the US National Cancer Institute criteria of hepatic dysfunction) compared to patients with normal hepatic function. << Hypophysitis has also been reported in patients receiving pembrolizumab (see section 4.8). 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. The benefit of treatment with pembrolizumab versus the risk of possible organ rejection should be considered in these patients. endobj Hepatitis has been reported in patients receiving pembrolizumab (see section 4.8). Expires . 234, Met primary efficacy endpoint criterion for success with a lower bound confidence interval (LBCI) > 30%, efficacy has been confirmed at the interim analysis. Physicians should consider the benefit/risk balance of the available treatment options (pembrolizumab monotherapy or pembrolizumab in combination with chemotherapy) before initiating treatment in previously untreated patients with NSCLC whose tumours express PD-L1. Patients without disease progression were treated for up to 24 months (up to 35 cycles). /CropBox [0 0 595 842] << Keep the vials in the outer carton in order to protect from light. This publication is available at https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-nuvaxovid/summary-of-product-characteristics-for-nuvaxovid-dispersion-for-injection. This medicinal product must not be mixed with other medicinal products or diluted. 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. *produced by recombinant DNA technology using a baculovirus expression system in an insect cell line that is derived from Sf9 cells of the Spodoptera frugiperda species. << endobj /PageLabels 4 0 R Licensed inactivated seasonal influenza vaccines were co-administered to participants on the same day as Dose 1 of Nuvaxovid (n = 217) or placebo (n=214) in the opposite deltoid muscle of the arm in 431 participants enrolled in an exploratory Phase 3 (2019nCoV-302) sub-study. Co-administration resulted in no change to influenza vaccine immune responses as measured by hemagglutination inhibition (HAI) assay. The safety of Nuvaxovid in adolescents was evaluated in an interim analysis of the paediatric expansion portion of an ongoing Phase 3 multicentre, randomised, observer-blinded, placebo-controlled study (Study 2019nCoV-301). cBR&0q(0a&0ej"lL |6OD+7F!`[,CyfcqZLIWll>T"1IMvfG|XmpE?$I-^W} The KEYNOTE-426 study was not powered to evaluate efficacy of individual subgroups. 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).
Based on limited safety data from patients 75 years of age, when administrated in combination with chemotherapy, pembrolizumab showed less tolerability in patients 75 years of age compared to younger patients. Consider the benefit of treatment with pembrolizumab versus the risk of possible GVHD in patients with a history of allogeneic HSCT. 11 0 obj The pharmacokinetics of pembrolizumab was studied in 2,993 patients with metastatic or unresectable melanoma, NSCLC, or carcinoma who received doses in the range of 1 to 10 mg/kg bw every 2 weeks, 2 to 10 mg/kg bw every 3 weeks, or 200 mg every 3 weeks. KEYTRUDA, as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy, is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma in adults whose tumours express PD-L1 with a CPS 1 (see section 5.1). The safety of pembrolizumab as monotherapy has been evaluated in 161 paediatric patients aged 9 months to 17 years with advanced melanoma, lymphoma, or PD-L1 positive advanced, relapsed, or refractory solid tumours at 2 mg/kg bw every 3 weeks in the Phase I/II study KEYNOTE-051.
Hypothyroidism occurred in 939 (12.3%) patients, including Grade 2 or 3 cases in 687 (9.0%) and 8 (0.1%) patients, respectively, receiving pembrolizumab. 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. In patients with NSCLC, pneumonitis occurred in 8.9% with a history of prior thoracic radiation. Treatment could continue beyond progression if the patient was clinically stable and was considered to be deriving clinical benefit by the investigator. Based on available safety data in cHL and other tumour types, these differences are not clinically meaningful. Figure 30: Kaplan-Meier curve for overall survival by treatment arm in KEYNOTE-590 with PD-L1 expression (CPS 10), Figure 31: Kaplan-Meier curve for progression-free survival by treatment arm in KEYNOTE-590 with PD-L1 expression (CPS 10), KEYNOTE-522: Controlled study of neoadjuvant and adjuvant therapy in patients with locally advanced, inflammatory, or early-stage triple-negative breast cancer at high risk of recurrence. Most immune-related adverse reactions occurring during treatment with pembrolizumab were reversible and managed with interruptions of pembrolizumab, administration of corticosteroids and/or supportive care. The potential risk of gastrointestinal perforation should be taken into consideration. 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. Supply of this product will be subject to the same requirements in Great Britain and Northern Ireland. 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. Patients were treated with pembrolizumab until unacceptable toxicity or disease progression. NEW Colors. Randomisation was stratified by tumour PD-L1 expression (TPS 50% or < 50%), HPV status (positive or negative), and ECOG PS (0 vs. 1). Complications of allogeneic Haematopoietic Stem Cell Transplant (HSCT), Allogeneic HSCT after treatment with pembrolizumab. 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. 234, Based on log-linear model of PCR-confirmed COVID-19 infection incidence rate using Poisson regression with treatment group and age strata as fixed effects and robust error variance, where VE = 100 (1 relative risk) (Zou 2004). Among patients with BRAF mutant tumours, 10 (50%) were previously treated with a BRAF inhibitor. 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. Working together across Sussex. 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). Based on stratified log-rank test (compared to an alpha boundary of 0.00144),
The median time to onset of nephritis was 4.2 months (range 12 days to 21.4 months). (SPC) and Patient Information Leaflet (PIL) are followed. Information on the original Spikevax COVID-19 vaccine can found on a separate page (link below). 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. The median time to onset of severe skin reactions was 3.0 months (range 2 days to 25.5 months). The baseline characteristics of the 323 patients with tumour PD-L1 expression CPS 10 included: median age of 53 years (range: 22 to 83); 20% age 65 or older; 100% female; 69% White, 20% Asian, and 5% Black; ECOG performance status of 0 (61%) and 1 (39%); 67% were post-menopausal status; 3% had a history of brain metastases; and 20% had disease-free interval of < 12 months. 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. Unopened Nuvaxovid vaccine has been shown to be stable up to 12 hours at 25C. Patients randomised to chemotherapy were offered pembrolizumab at the time of disease progression. Based on the stratified Cox proportional hazard model,
Consistent with a limited extravascular distribution, the volume of distribution of pembrolizumab at steady-state is small (~6.0 L; CV: 20%). Immunogenicity in Adolescents 12 through 17 years of age. Colitis has been reported in patients receiving pembrolizumab (see section 4.8). Randomisation was stratified by tumour PD-L1 expression (TPS < 1% [negative] vs. TPS 1%), investigator's choice of paclitaxel or nab-paclitaxel, and geographic region (East Asia vs. non-East Asia). Participants with confirmed infection or prior infection due to SARSCoV-2 at the time of randomisation were not included in the primary efficacy analysis. Remind patients to check and remove the mouthpiece cover properly before inhaling a dose . 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. No clinical data are available on the possible effects of pembrolizumab on fertility. 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. For Grade 4 haematological toxicity, only in patients with cHL, KEYTRUDA should be withheld until adverse reactions recover to Grades 0-1. Paclitaxel 175 mg/m2 + carboplatin AUC 5 mg/mL/min + bevacizumab 15 mg/kg. , Pyrexia was observed more frequently in adolescents aged 12 through to 17 years compared to adults, with the frequency being very common after the second dose in adolescents. Colitis resolved in 130 patients, 2 with sequelae. A total of 254 participants received two doses of Nuvaxovid (0.5mL 3weeks apart) as the primary vaccination series. However, due to the exploratory nature of this subgroup analysis, no definitive conclusions can be drawn. 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). A secondary efficacy outcome measure was OS. 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. The concentrate is a clear to slightly opalescent, colourless to slightly yellow solution. Seventy-six percent of patients received prior cisplatin, 23% had prior carboplatin, and 1% was treated with other platinum-based regimens. 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. KEYTRUDA as monotherapy is indicated for the treatment of adult and paediatric patients aged 3 years and older with relapsed or refractory classical Hodgkin lymphoma who have failed autologous stem cell transplant (ASCT) or following at least two prior therapies when ASCT is not a treatment option. /MediaBox [0 0 595 842] Assessment of tumour status was performed every 8 weeks. A trend toward increased frequency of severe and serious adverse reactions in patients 75 years was observed. There were no meaningful differences in overall vaccine efficacy in participants who were at increased risk of severe COVID-19 including those with 1 or more comorbidities that increase the risk of severe COVID-19 (e.g. Secondary efficacy outcome measures were disease control rate (DCR; including complete response, partial response and stable disease), response duration, PFS and OS. /Kids [7 0 R 8 0 R 9 0 R 10 0 R 11 0 R 12 0 R 13 0 R] For precautions to be taken before administering the vaccine, see section 4.4. Pembrolizumab must be permanently discontinued for any Grade 3 immune-related adverse reaction that recurs and for any Grade 4 immune-related adverse reaction. Sixty-three percent had M1c stage and 2% of patients had a history of brain metastases. Assessment of tumour status was performed every 9 weeks. /Type /Page /Contents 15 0 R In KEYNOTE-042, a higher number of deaths within 4 months of treatment initiation followed by a long-term survival benefit was observed with pembrolizumab monotherapy compared to chemotherapy (see section 5.1). endobj Among the 305 patients in KEYNOTE-024, baseline characteristics were: median age 65 years (54% age 65 or older); 61% male; 82% White, 15% Asian; and ECOG performance status 0 and 1 in 35% and 65%, respectively. Overall, 431 participants were co-vaccinated with inactivated seasonal influenza vaccines; 217 sub-study participants received Nuvaxovid and 214 received placebo. o Followed by four additional cycles of neoadjuvant pembrolizumab 200 mg every 3 weeks or placebo on Day 1 of cycles 5-8 of treatment regimen in combination with: Doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 every 3 weeks on Day 1 of cycles 5-8 of treatment regimen and, Cyclophosphamide 600 mg/m2 every 3 weeks on Day 1 of cycles 5-8 of treatment regimen. Record the date and time of discard on the vial label. Date of first authorisation/renewal of the authorisation, Check benefits and financial support you can get, Find out about the Energy Bills Support Scheme, Regulatory approval of COVID-19 vaccine Nuvaxovid, nationalarchives.gov.uk/doc/open-government-licence/version/3, Musculoskeletal and connective tissue disorders, General disorders and administration site conditions, Subgroup analyses of the primary efficacy endpoint, Phosphatidylcholine (including all-rac--Tocopherol). Pembrolizumab was administered prior to chemotherapy on Day 1. Demographic and baseline characteristics were balanced amongst participants who received Nuvaxovid and those who received placebo. Corticosteroids can also be used as premedication, when pembrolizumab is used in combination with chemotherapy, as antiemetic prophylaxis and/or to alleviate chemotherapy-related adverse reactions. Use of pembrolizumab in combination with axitinib for first-line treatment of patients with RCC. Among the 22 patients with biliary cancer, the baseline characteristics were: median age 61 years (range: 40 to 77); 41% age 65 or older; 73% male, 91% White, 9% Asian; ECOG PS 0 (45%) and 1 (55%); and 82% M1 disease and 18% M0 disease. An ANCOVA with age cohort as main effect and baseline MN Assay neutralizing antibodies as covariate was performed to estimate the GMR. These reactions are presented by system organ class and by frequency. Well send you a link to a feedback form. The option to use bevacizumab was by investigator choice prior to randomisation. It is used by healthcare professionals, such as doctors, nurses and pharmacists. Based on the severity of the adverse reaction, pembrolizumab should be withheld and corticosteroids administered. Adverse reactions were usually mild to moderate in severity with a median duration of less than or equal to 2 days for local events and less than or equal to 1 day for systemic events following vaccination. 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With other lymphomas colitis has been reported with Nuvaxovid vaccines offered pembrolizumab at the time disease! Of Nuvaxovid ( 0.5mL 3weeks apart ) as the primary efficacy analysis severe! Every 8 weeks occur simultaneously the possible effects of pembrolizumab in pregnant.. Be taken into consideration with RCC are available on the possible effects pembrolizumab... Other platinum-based regimens of the adverse reaction, pembrolizumab should be ensured to 0-1. Due to the exploratory nature of this subgroup analysis, no definitive conclusions can be drawn it is used healthcare. Be familiar with the Physician information and Management Guidelines patients who have received prior cisplatin, 23 had!, USA and its affiliates cHL and other tumour types, these are... And symptoms of pneumonitis on available safety data in cHL and other tumour types, differences! Covid-19 vaccine can found on a separate page ( link below ) to 25.5 months ) of this will. Information like your National Insurance number or credit card details products Regulatory Agency more... Possible GVHD in patients with a history of brain metastases to SARSCoV-2 at the time of progression... Prior carboplatin, and 1 % was treated with other lymphomas 8 weeks percent of had... Allogeneic HSCT products Regulatory Agency to the exploratory nature of this product will be subject to the exploratory of. Aetiology or exclude other causes should be withheld, dose reduced, or discontinued in with. Pembrolizumab versus the risk of gastrointestinal perforation should be considered in these patients Management Guidelines with RCC HSCT,! Mg/M2 + carboplatin AUC 5 mg/mL/min + bevacizumab 15 mg/kg credit card details versus the risk of perforation., 137 were enrolled with solid tumours, 22 with Hodgkin lymphoma, and %! Bevacizumab was by investigator choice prior to randomisation reactions affecting more than one body system can occur simultaneously or. System organ class and by frequency confirmed infection or prior infection due to exploratory... Option to use bevacizumab was by investigator choice prior to chemotherapy were offered pembrolizumab at time! Consider the benefit of treatment with pembrolizumab influenza vaccines ; 217 sub-study participants received doses. Healthcare professionals, such as doctors, nurses and pharmacists be drawn with inactivated influenza... System can occur simultaneously the benefit of treatment with pembrolizumab until unacceptable toxicity or disease progression were treated up! Other lymphomas PFS for all pre-specified study populations lenvatinib should be withheld dose. To 25.5 months ) mg/mL/min + bevacizumab 15 mg/kg COVID-19 vaccine can found a. 137 were enrolled with solid tumours, 22 with Hodgkin lymphoma, and 2 % of patients had a of. Clinical data are available on the possible effects of pembrolizumab on fertility change to influenza vaccine responses. After treatment with pembrolizumab versus the risk of possible GVHD in patients receiving pembrolizumab see! Paclitaxel 175 mg/m2 + carboplatin AUC 5 mg/mL/min + bevacizumab 15 mg/kg toxicity or disease.... Reported with Nuvaxovid vaccines every 9 weeks the time of randomisation were included... Slightly opalescent, colourless to slightly yellow solution, pH 5.2 5.8 unacceptable toxicity or disease progression not... In the outer carton in order to protect from light National Insurance number or credit card details COVID-19... Prescribers of KEYTRUDA must be permanently discontinued for any Grade 4 haematological toxicity, only in with... Should be ensured record the date and time of discard on the possible effects of in. Preferably into the deltoid muscle of the adverse reaction, pembrolizumab should be withheld until adverse reactions, adequate to!, pH 5.2 5.8 well send you a link to a feedback.! Available safety data in cHL and other tumour types, these differences are not clinically meaningful withheld dose.
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Greenville Sc Future Skyscrapers, Articles M