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1.
Pediatric Critical Care Medicine ; 02:02, 2022.
Article in English | MEDLINE | ID: covidwho-2018352

ABSTRACT

OBJECTIVES: The COVID-19 pandemic resulted in adaptations to pediatric resuscitation systems of care. The objective of this study was to determine the temporal association between the pandemic and pediatric in-hospital cardiac arrest (IHCA) process of care metrics, cardiopulmonary resuscitation (cardiopulmonary resuscitation) quality, and patient outcomes. DESIGN: Multicenter retrospective analysis of a dataset comprising observations of IHCA outcomes pre pandemic (March 1, 2019 to February 29, 2020) versus pandemic (March 1, 2020 to February 28, 2021). SETTING: Data source was the ICU-RESUScitation Project ("ICU-RESUS;" NCT028374497), a prospective, multicenter, cluster randomized interventional trial. PATIENTS: Children (<= 18 yr) who received cardiopulmonary resuscitation while admitted to the ICU and were enrolled in ICU-RESUS. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 429 IHCAs meeting inclusion criteria, occurrence during the pandemic period was associated with higher frequency of hypotension as the immediate cause of arrest. Cardiac arrest physiology, cardiopulmonary resuscitation quality metrics, and postarrest physiologic and quality of care metrics were similar between the two periods. Survival with favorable neurologic outcome (Pediatric Cerebral Performance Category score 1-3 or unchanged from baseline) occurred in 102 of 195 subjects (52%) during the pandemic compared with 140 of 234 (60%) pre pandemic (p = 0.12). Among survivors, occurrence of IHCA during the pandemic period was associated with a greater increase in Functional Status Scale (FSS) (i.e., worsening) from baseline (1 [0-3] vs 0 [0-2];p = 0.01). After adjustment for confounders, IHCA survival during the pandemic period was associated with a greater increase in FSS from baseline (+1.19 [95% CI, 0.35-2.04] FSS points;p = 0.006) and higher odds of a new FSS-defined morbidity (adjusted odds ratio, 1.88 [95% CI, 1.03-3.46];p = 0.04). CONCLUSIONS: Using the ICU-RESUS dataset, we found that relative to the year prior, pediatric IHCA during the first year of the COVID-19 pandemic was associated with greater worsening of functional status and higher odds of new functional morbidity among survivors.

2.
Computers ; 11(7):23, 2022.
Article in English | Web of Science | ID: covidwho-1979146

ABSTRACT

The inclusion of information and communication technologies in education has become a priority for all educational models, particularly for higher education institutes that have observed the need to integrate these technologies in the classroom. However, to guarantee educational quality and learning, establishing a process that allows the identification of the response of the students towards its use is necessary. For this purpose, there are several works that address the issue and have determined the functionality of these technologies, but each environment is different, and this is recognized by the higher education institutes of Ecuador that have limited economic, technological, and academic resources. This work seeks to create a method that allows the needs and doubts of students about the use of educational technologies in the classroom to be established without affecting their academic performance. To perform this, a process has been designed that identifies learning needs through the validation of data obtained from surveys and a comparison of two groups of students, in which one group makes use of technologies in the classroom and the other group uses a model of traditional education. By obtaining the results of the analysis, the method determines the impact of technology on learning.

3.
Journal of Thoracic Oncology ; 16(10):S892, 2021.
Article in English | EMBASE | ID: covidwho-1482771

ABSTRACT

Introduction: Stage IIIB-IV non-small cell lung cancer patients with mutations in the EGF receptor gene (EGFR) usually derive clinical benefit from to tyrosine kinase inhibitors (EGFR TKIs) but ultimately relapse. In preclinical studies, we have showed that anti-EGF antibodies generated by vaccination significantly increased the antitumor activity of TKIs in EGFR-mut cell lines, blocking EGFR, Erk1/2, Akt and STAT3 activation and delaying emergence of resistance. Based on these findings, the EPICAL trial was initiated (ClinicalTrials.gov number, NCT03623750). Methods: The EPICAL was a single arm, phase 1b, single arm study to evaluate the safety and efficacy of first line anti-EGF vaccination combined with afatinib. The trial enrolled advanced NSCLC patients with sensitizing EGFR mutations confirmed in a central laboratory. Patients received 40 mg/day of afatinib and five intramuscular anti-EGF vaccinations every 14 days and then every three months until progression. Four medical centers in Spain participated, with a target enrollment of 30 patients. However, the COVID-19 outbreak forced an early termination of the study in March 2020 with only 23 patients included. Serial blood samples were collected and used to evaluate the levels of selected growth factors by ELISA and biological activity by addition of sera to in vitro cultures of EGFR-mut cells followed by Western blotting. Results: Of the 23 patients enrolled in the trial, nine (39%) had exon 19 in-frame deletions, twelve (52%) exon 21 substitutions and two (9%) exon 18 missense mutations. Combination treatment was well tolerated and no SAES related to anti-EGF vaccination were reported. Objective response and disease control rates were 78.3% (95%CI=53.6-92.5) and 95.7% (95%CI=78.1-99.9), respectively. At data cut-off, with a median follow-up of 11.4 months (95%CI=8.1-15.2), the median progression-free survival was 17.4 months (95% CI=13.22-NA) and median survival not reached (95% CI=15.21-NA). Median PFS for patients with exon 19 deletions and exon 21 point mutations were 13.9 months (95%CI=8.7-NR) and 17.4 months (95%CI=13.2-NR), respectively. Three months after initiation of treatment, high titers of anti-EGF antibodies were detected in all patients and serum EGF and TGFα levels were found to be significantly lower compared to baseline levels. Finally, treatment with post-vaccination patient’s sera inhibited EGFR, AKT and ERK1/2 phosphorylation in EGFR-mut cells growing in vitro. Conclusion: The combination of an anti–EGF vaccine with afatinib is well tolerated and induces a sustained immunogenic effect. Vaccination against EGF might enhance the clinical efficacy of EGFR TKIs. Keywords: anti-EGF vaccination, EGFR-mutant non-small cell lung cancer, EGFR inhibitors

4.
Journal of Thoracic Oncology ; 16(10):S883-S884, 2021.
Article in English | EMBASE | ID: covidwho-1474794

ABSTRACT

Introduction: There are currently no predictive biomarkers for long-term survival after neoadjuvant chemoimmunotherapy. However, the identification of non-small lung cancer (NSCLC) patients who obtain long-term benefit from chemoimmunotherapy is essential to optimize therapies. Methods: Using samples from NADIM clinical trial (NCT03081689), in which resectable stage IIIA NSCLC patients were treated with neoadjuvant chemo-immunotherapy with nivolumab, we have evaluated the capacity of ctDNA levels before treatment initiation to predict overall survival (OS) and progression-free survival (PFS) by calculating Harrell’s C-statistic and we compare its predictive value with classical survival surrogates as the pathological response and clinical response assessed according to RECIST criteria v.1.1. The ctDNA was analyzed by NGS, using the Oncomine Pan-Cancer Cell-Free Assay™ (Thermo Fisher Scientific®). To explore the prognostic value of the amount of ctDNA at baseline, for each positive plasma sample, we calculated the sum of the mutant allele frequency (MAF) for all detected mutations. Patients who died from COVID19 were excluded from this analysis. Results: In our study, clinical responses based on RECIST criteria were not predictive for OS or PFS. On the contrary, in the multivariate analysis, patients with low ctDNA levels (<1% MAF), in the baseline sample, had significantly improved PFS and OS than patients in whom the opposite situation occurred (adjusted HR: 0.22;95%CI: 0.06-0.75;P=0.016 and adjusted HR: 0.04;95%CI: 0.00-0.45;P=0.008 for PFS and OS, respectively). The adjusted C-statistic (c) to predict PFS for ctDNA was 0.68 (95%CI: 0.51-0.84), which was superior to that of RECIST criteria (c=0.61;95%CI: 0.45-0.78) and similar to that of pathological response (c=0.68;95%CI: 0.52-0.84). Similarly, baseline ctDNA levels predicted OS (c=0.85;95%CI: 0.72-0.99) better than RECIST criteria (c=0.68;95%CI: 0.44-0.93). Conclusion: Pre-treatment ctDNA levels predicted more accurately long-term survival than radiological assessments in NADIM study and might be useful for the design of new clinical trials.

5.
Journal of Thoracic Oncology ; 16(10):S883, 2021.
Article in English | EMBASE | ID: covidwho-1474793

ABSTRACT

Introduction: Neoadjuvant chemoimmunotherapy been shown to be highly effective in resectable stage IIIA NSCLC. Now we provide long term survival data Methods: This was an open-label, multicentre, single-arm phase 2 trial in which patients with histologically or cytologically documented stage IIIA NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 and who were deemed locally to be surgically resectable by a multidisciplinary clinical team were treated with neoadjuvant intravenous paclitaxel (200 mg/m2) and carboplatin (area under curve 6;6 mg/mL per min) plus nivolumab (360 mg) on day 1 of each 21-day cycle, for three cycles before surgical resection, followed by adjuvant intravenous nivolumab monotherapy for 1 year (240 mg every 2 weeks for 4 months, followed by 480 mg every 4 weeks for 8 months). Here we report progression-free survival (PFS) and Overall survival (OS) at 36 and 42 months, assessed in the modified intention-to-treat population (ITT), which included all patients who received neoadjuvant treatment, and in the per-protocol population (PP), which included all patients who had tumour resection and received at least one cycle of adjuvant treatment. Results: Median follow-up time was 37.9 months (95%CI: 36.7-40.7), with a 94% maturity at 36 months. Among the ITT population (N=46), 37 patients, constituting the PP population, received subsequent adjuvant therapy. Of them, 27 (58.7%) patients completed the adjuvant treatment (16 cycles), 10 (21.7%) patients received between 3 and 15 cycles of adjuvant therapy, and 9 (19.6%) patients did not receive adjuvant therapy. At the time of data cutoff (March 2021), progression disease was diagnosed in 14 patients and 9 deaths were recorded in the ITT population. Of these, three deaths corresponded to patients who did not undergo surgery and had disease progression, four deaths corresponded to patients who underwent surgery and had disease progression, and the two remaining deaths corresponded to patients who were diagnosed as being disease free but died from COVID19 infection. Notably, among patients who could not undergo surgery (N=5), one of them is still alive and with no evidence of disease. PFS at 36 and 42 months in the ITT population were 69.6% (95%CI: 54.1-80.7), in both cases. Similarly, PFS at 36 and 42 in the PP population were 81.1% (95%CI: 64.4-90.5) in both cases. The percentage of patients who were alive at 36 and 42 months in the modified ITT population were 81.86% (95% CI: 66.8-90.6) and 78.94% (95%CI: 63.1-88.6), respectively. Likewise, OS at 36 and 42 months in the PP population was 91.0% (95%CI: 74.2-97.0) and 87.3% (95%CI: 69.3-95.1), respectively. Conclusion: The efficacy of nivolumab in combination with platinum-based chemotherapy in patients with resectable stage IIIA NSCLC is clearly supported by long term survival data. Keywords: NADIM trial, neoadjuvant chemo-therapy, long term survival

6.
Annals of Oncology ; 32:S1325, 2021.
Article in English | EMBASE | ID: covidwho-1446385

ABSTRACT

Background: OSE2101 (Tedopi®) is an anticancer vaccine (modified epitopes restricted to HLA-A2+ from 5 tumor-associated antigens). Atalante-1 is a randomized phase 3 trial of OSE2101 vs Standard of Care (SoC docetaxel or pemetrexed) in pretreated HLA-A2+ patients with advanced NSCLC, with IO as last treatment. Methods: EGFR and ALK negative NSCLC patients, ECOG PS 0-1 were randomized 2:1 to receive OSE2101 subcutaneously Q3W for 6 cycles, followed by maintenance Q8W for 1 year and Q12W until progression, versus SoC (docetaxel or pemetrexed Q3W). Primary endpoint was OS (initial hypothesis of HR 0.7 for 401 pts). Secondary endpoints were disease control rate (DCR), quality of life (QoL - EORTC QLQ-C30/LC13), and Progression free survival (PFS). Toxicities were reported using CTCAE 5.0. Positive pre-specified analyses (ESMO 2020 #1260MO) identified a Population of Interest (PoI) comprised by patients with IO secondary resistance defined as failure after a minimum of 12 weeks IO in sequential CT-IO patients. Due to the risk of COVID-19 pandemic on data integrity, the study was stopped prematurely following IDMC recommendations. PoI was chosen as primary population for the final analysis. Results: 219 pts were enrolled: median age 65 years, 29% female, 10% never-smoker, 70% non-squamous. 183 (84%) pts received sequential CT-IO from whom 118 pts (54%) complied with the definition of PoI, with otherwise similar characteristics that the overall population. In PoI, mOS was 11.1 mo for OSE2101 vs 7.5 for SoC [HR 0.59 (0.38-0.91) p= 0.02]. 6 mo-DCR 25% vs 24% (NS), mPFS 2.7 mo vs 3.4 (NS), ORR 8% vs 18% (p=0.07). Post progression survival was 7.7 mo vs 4.6 [HR 0.46 p= 0.004], time to worsening ECOG PS 8.6 mo vs 3.3 [HR 0.45 p= 0.0005]. In the total population, HR for OS was 0.86 (0.62-1.19) p=0.36. QoL Global Health Status was maintained for OSE2101 (p<0.05). Severe Adverse Events were 38% vs 68% (p<0.001). There was no TEAE of concern in the OSE2101 group. Conclusions: OSE2101 had a favorable benefit/risk of versus SoC in advanced HLA-A2+ NSCLC patients. HR for OS improved from 0.86 to 0.59 in patients with secondary resistance to IO with a meaningful gain of median OS of 3.6 months with OSE2101. Clinical trial identification: EudraCT 2015-003183-36;NCT02654587. Editorial acknowledgement: We thank Pierre Attali (Medical Expert, MD), François Montestruc (Statistics, eXYSTATt) and Berangere Vasseur (MD, OSE Immunotherapeutics) for their support in the writing of the abstract. Legal entity responsible for the study: OSE Immunotherapeutics. Funding: OSE Immunotherapeutics. Disclosure: B. Besse: Financial Interests, Institutional, Research Grant: AbbVie;Financial Interests, Institutional, Research Grant: Amgen;Financial Interests, Institutional, Research Grant: AstraZeneca;Financial Interests, Institutional, Research Grant: BEIGENE;Financial Interests, Institutional, Research Grant: Blue Print Medicines;Financial Interests, Institutional, Research Grant: BMS;Financial Interests, Institutional, Research Grant: Boehringer Ingelheim;Financial Interests, Institutional, Research Grant: Cellgene;Financial Interests, Institutional, Research Grant: Cristal Therapeutics;Financial Interests, Institutional, Research Grant: Daiichi Sankyo;Financial Interests, Institutional, Research Grant: Eli Lilly;Financial Interests, Institutional, Research Grant: GSK;Financial Interests, Institutional, Research Grant: Inivata;Financial Interests, Institutional, Research Grant: Janssen;Financial Interests, Institutional, Research Grant: Onxeo;Financial Interests, Institutional, Research Grant: OSE Immunotherapeutics;Financial Interests, Institutional, Research Grant: Pfizer;Financial Interests, Institutional, Research Grant: Roche-Genentech;Financial Interests, Institutional, Research Grant: Sanofi;Financial Interests, Institutional, Research Grant: Takeda;Financial Interests, Institutional, Research Grant: Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: 4D Pharma;Financial Interests, Institutional, Res arch Grant: Aptitude Health;Financial Interests, Institutional, Research Grant: Cergentis. M.R. Garcia Campelo: Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: Bristol-Myers;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: Boehringer Ingelheim;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Lilly;Financial Interests, Personal, Advisory Board: Takeda;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Advisory Role: MSD;Financial Interests, Personal, Advisory Role: Bristol-Myers;Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Boehringer Ingelheim;Financial Interests, Personal, Advisory Role: Pfizer;Financial Interests, Personal, Advisory Role: Novartis;Financial Interests, Personal, Advisory Role: AstraZeneca;Financial Interests, Personal, Advisory Role: Lilly;Financial Interests, Personal, Advisory Role: Takeda;Financial Interests, Personal, Advisory Role: Janssen;Financial Interests, Personal, Invited Speaker: MSD;Financial Interests, Personal, Invited Speaker: Bristol-Myers;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim;Financial Interests, Personal, Invited Speaker: Pfizer;Financial Interests, Personal, Invited Speaker: Novartis;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Lilly;Financial Interests, Personal, Invited Speaker: Takeda;Financial Interests, Personal, Invited Speaker: Janssen. E. Quoix: Financial Interests, Personal, Speaker’s Bureau: Shugaï;Financial Interests, Institutional, Principal Investigator: Roche;Financial Interests, Institutional, Principal Investigator: OSE Immunotherapeutics;Financial Interests, Institutional, Principal Investigator: Novartis;Financial Interests, Institutional, Principal Investigator: BMS;Financial Interests, Institutional, Principal Investigator: GSK. E. Felip: Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Advisory Board: BeiGene;Financial Interests, Personal, Advisory Board: Boehringer Ingelheim;Financial Interests, Personal, Advisory Board: Bristol Myers Squibb;Financial Interests, Personal, Advisory Board: Eli Lilly;Financial Interests, Personal, Advisory Board: F. Hoffmann-La Roche;Financial Interests, Personal, Advisory Board: GlaxoSmithKline;Financial Interests, Personal, Advisory Board: Janssen;Financial Interests, Personal, Advisory Board: Medical Trends;Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Board: Merck Serono;Financial Interests, Personal, Advisory Board: PEPTOMYC;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Puma;Financial Interests, Personal, Advisory Board: Regeneron;Financial Interests, Personal, Advisory Board: Sanofi;Financial Interests, Personal, Advisory Board: Syneos Health;Financial Interests, Personal, Advisory Board: Takeda;Financial Interests, Personal, Speaker’s Bureau: Amgen;Financial Interests, Personal, Speaker’s Bureau: AstraZeneca;Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb;Financial Interests, Personal, Speaker’s Bureau: Eli Lilly;Financial Interests, Personal, Speaker’s Bureau: F. Hoffmann-La Roche;Financial Interests, Personal, Speaker’s Bureau: Janssen;Financial Interests, Personal, Speaker’s Bureau: Medscape;Financial Interests, Personal, Speaker’s Bureau: Merck Sharp & Dohme;Financial Interests, Personal, Speaker’s Bureau: Merck Serono;Financial Interests, Personal, Speaker’s Bur au: PeerVoice;Financial Interests, Personal, Speaker’s Bureau: Pfizer;Financial Interests, Personal, Speaker’s Bureau: Springer;Financial Interests, Personal, Speaker’s Bureau: Touch Medical;Financial Interests, Personal, Other, Independent Member of the Board: Grifols;Non-Financial Interests, Institutional, Research Grant: Grant For Oncology Innovation (GOI);Non-Financial Interests, Institutional, Research Grant: Fundación Merck Salud. F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: AZ;Financial Interests, Personal, Invited Speaker: MSD;Financial Interests, Personal, Invited Speaker: BMS;Financial Interests, Personal, Invited Speaker: Pfizer;Financial Interests, Personal, Invited Speaker: Takeda;Financial Interests, Personal, Invited Speaker: Lilly;Financial Interests, Personal, Invited Speaker: Bayer;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: AZ;Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: Pfizer;Financial Interests, Personal, Advisory Board: Takeda;Financial Interests, Personal, Advisory Board: Lilly;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Advisory Board: Amgen;Financial Interests, Personal, Advisory Board: Sanofi. F. Denis: Financial Interests, Personal, Invited Speaker: Merck;Financial Interests, Personal, Invited Speaker: Chugai;Financial Interests, Personal, Invited Speaker: AstraZeneca;Financial Interests, Personal, Invited Speaker: Roche. W. Hilgers: Financial Interests, Personal, Advisory Role: Janssen;Financial Interests, Personal, Advisory Role: AstraZeneca;Financial Interests, Personal, Invited Speaker: MSD. S. Viteri: FinancialInterests, Personal, Full or part-time Employment: Pangaea Oncology;Financial Interests, Personal, Advisory Board: AbbVie;Financial Interests, Personal, Advisory Board: Roche;Financial Interests, Personal, Advisory Board: BMS;Financial Interests, Personal, Advisory Board: MSD;Financial Interests, Institutional, Research Grant: Roche;Financial Interests, Institutional, Research Grant: AbbVie;Financial Interests, Institutional, Research Grant: OSE Immunotherapeutics;Financial Interests, Institutional, Research Grant: Merck;Financial Interests, Institutional, Research Grant: Janssen;Financial Interests, Institutional, Research Grant: Boehringer Ingelheim;Financial Interests, Institutional, Research Grant: Boston Pharmaceuticals;Financial Interests, Institutional, Research Grant: Exelexis;Financial Interests, Institutional, Research Grant: Novocure;Financial Interests, Institutional, Research Grant: Medimmune;Financial Interests, Personal, Other, Travel accomodation expenses: Roche;Financial Interests, Personal, Other, Travel accomodation expenses: Merck;Financial Interests, Personal, Other, Travel accomodation expenses: MSD;Financial Interests, Personal, Other, Travel accomodation expenses: BMS;Financial Interests, Personal, Other, Travel accomodation expenses: OSE Immunotherapeutics. W. Schuette: Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Lilly;Financial Interests, Personal, Advisory Role: Amgen;Financial Interests, Personal, Advisory Role: Merck. A. Zer: Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Invited Speaker: BMS;Financial Interests, Personal, Invited Speaker: MSD;Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker: Takeda;Financial Interests, Personal, Stocks/Shares: Nixio;Non-Financial Interests, Institutional, Research Grant: BMS. D. Costantini: Financial Interests, Personal, Full or part-time Employment: OSE Immunotherapeutics;Financial Interests, Personal, Stocks/Shares: OSE Immunotherapeutics. R. Dziadziuszko: Financial Interests, Personal, Advisory Role: F. Hoffman- La Roche Ltd;Financial Intere ts, Personal, Advisory Role: AstraZeneca;Financial Interests, Personal, Advisory Role: Pfizer;Financial Interests, Personal, Advisory Role: Novartis;Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme;Financial Interests, Personal, Advisory Role: Foundation Medicine Takeda;Financial Interests, Personal, Advisory Role: Seattle Genetics;Financial Interests, Personal, Advisory Role: Roche;Financial Interests, Personal, Advisory Role: Boehringer Ingelheim;Financial Interests, Personal, Advisory Board: Bayer;Financial Interests, Personal, Principal Investigator: F. Hoffmann-La Roche Ltd;Financial Interests, Personal, Principal Investigator: Merck Sharp & Dohme;Financial Interests, Personal, Principal Investigator: Amgen;Financial Interests, Personal, Principal Investigator: Janssen;Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb;Financial Interests, Personal, Principal Investigator: AstraZeneca;Non-Financial Interests, Institutional, Product Samples: F. Hoffmann-La Roche Ltd;Non-Financial Interests, Institutional, Product Samples: Novartis;Non-Financial Interests, Institutional, Product Samples: Pfizer. All other authors have declared no conflicts of interest.

7.
Annals of Oncology ; 31:S814-S815, 2020.
Article in English | EMBASE | ID: covidwho-801393

ABSTRACT

Background: Tedopi® is an anticancer vaccine with modified neoepitopes restricted to HLA-A2+ targeting five tumor-associated antigens frequently expressed in lung cancer: CEA, HER2, MAGE2, MAGE3 and P53. ATALANTE-1 was a randomized, open-label, 2-Step phase 3 study comparing the efficacy of Tedopi® with standard treatment (SoC) in HLA-A2+ NSCLC patients in 2nd or 3rd line treatment after progression on ICI. Methods: HLA-A2+ NSCLC patients, EGFR and ALK negative, having progressed to platinum-based chemotherapy (CT) and anti-PD(L)1, ECOG PS 0-1 were randomized 2:1 to receive Tedopi® subcutaneously Q3W for 6 cycles, followed by maintenance Q8W up to first year, then Q12W, or SoC (docetaxel 75 mg/m2 Q3W or pemetrexed 500 mg/m2 Q3W). The Step-1 hypotheses were based on the evaluation of 1y-OS rate (Fleming design: H0 futility boundary at 25%;H1 alternative efficacy: 40% of OS rate at 12 months). Step-2 was a superiority study with OS as primary endpoint. Results: At cutoff of February 2020, 99 patients (Tedopi® n=63;SoC n=36) were randomized and analyzable for Step-1. The 1y-OS was 29/63 (46%) [95%CI 33-59]) in Tedopi® group and 13/36 (36%) [95%CI 21-54] in SoC. The Step-1 endpoint has shown a lower limit of the 95% confidence interval above the futility boundary (25%) with an OS estimate of 10% above the estimate of SoC. Secondary endpoints and subgroup data will be further presented. Grade 3-4 related TEAEs were 11 % in Tedopi® group and 43 % in SoC. There was no related grade 5 TEAE. Related TEAE leading to withdrawal from the study were also less frequent in Tedopi® group (6%) versus SoC (14%). Due to the risk of COVID-19 pandemic on data integrity, following recommendation of the Independent Data Monitoring Committee and Steering Committee, the decision was taken to early terminate the study at Step-1 and definitely stop new accrual while continuing the OS follow-up in all patients. Conclusions: The Step-1 primary endpoint was positively achieved with a 1y-OS rate of 46% and a good safety profile. Step-1 results shown a favorable benefit/risk of Tedopi® over SoC as 2nd or 3rd line treatment in advanced HLA-A2+ NSCLC patients after failure to ICI. Clinical trial identification: EudraCT: 2015-003183-36;NCT02654587. Legal entity responsible for the study: OSE Immunotherapeutics. Funding: OSE Immunotherapeutics. Disclosure: G. Giaccone: Advisory/Consultancy: CStone;Advisory/Consultancy: Novartis;Advisory/Consultancy: Daiichi;Research grant/Funding (institution): Medimunne;Research grant/Funding (institution): Incyte. E. Felip: Advisory/Consultancy: AbbVie;Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;Advisory/Consultancy: Blueprint Medicine;Advisory/Consultancy, Speaker Bureau/Expert testimony: Boehringer Ingelheim;Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS;Advisory/Consultancy, Speaker Bureau/Expert testimony: Elli Lilly;Advisory/Consultancy: Guardant Health;Advisory/Consultancy: Janssen;Advisory/Consultancy: Merck KgaA;Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD;Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Advisory/Consultancy: Samsung;Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda;Advisory/Consultancy: GSK;Advisory/Consultancy: Bayer;Speaker Bureau/Expert testimony: Medscape;Speaker Bureau/Expert testimony: Prime Oncology;Speaker Bureau/Expert testimony: Touchime;Research grant/Funding (institution): Fundation Merck Salud;Advisory/Consultancy: Grifols. R. Garcia Campelo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;H noraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. F. DENIS: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Advisory/Consultancy: Shugai;Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: Bayer;Advisory/Consultancy: MSD;Advisory/Consultancy, Licensing/Royalties: Sivan. E. Quoix: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;Speaker Bureau/Expert testimony: Shugai;Travel/Accommodation/Expenses: Roche;Travel/Accommodation/Expenses: Takeda;Honoraria (self), interview at ASCO 2019: Medscape. A. Madroszyk: Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Travel/Accommodation/Expenses: Pfizer;Travel/Accommodation/Expenses: MSD. D. Debieuvre: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): MSD;Honoraria (self), Research grant/Funding (institution): AstraZeneca;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self): Shugai;Advisory/Consultancy, Research grant/Funding (institution): Pfizer;Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis;Research grant/Funding (institution): Lilly;Research grant/Funding (institution): Sandoz;Travel/Accommodation/Expenses: Boehringer Ingelheim. W. Hilgers: Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;Honoraria (self): MSD;Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen;Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas;Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Advisory/Consultancy: AstraZeneca;Advisory/Consultancy: Roche. T. Moran: Advisory/Consultancy: Roche;Advisory/Consultancy: Boehringer Ingelheim. D. Galetta: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Boehringer Ingelheim;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: MSD;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: BMS;Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: AstraZeneca. F. Cappuzzo: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: BMS;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Takeda;Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: MSD. G. Robinet: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: MSD;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZenaca;Advisory/Consultancy: BMS. S. Viteri: Full/Part-time employment: Pangaea Oncology;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): AbbVie;Honoraria (self), Travel/Accommodation/Expenses: MSD;Research grant/Funding (institution), Travel/Accommodation/Expenses: Ose Immunotherapeutics;Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck KgaA;Research grant/Funding (institution): Janssen;Research grant/Funding (institution): Boehringer Ingelheim;Research grant/Funding (institution): Boston Pharmaceuticals Research grant/Funding (institution): Exelexis;Research grant/Funding (institution): Novocure;Research grant/Funding (institution): MedImmune. N. Peled: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca;Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): Bayer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Boehringer Ingelheim;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: BMS;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Lilly;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Foundation Medicine;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Guardian 360;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Genesort;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Merck KgaA;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Novartis;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): NovellusDx;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Takeda. D. Costantini: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Officer/Board of Directors: OSEImmunotherapeutics. R. Dziadziuszko: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: AstraZeneca;Honoraria (self): Pfizer;Honoraria (self): Novartis;Honoraria (self): MSD;Honoraria (self): Foundation Medicine;Honoraria (self), Advisory/Consultancy: Takeda;Advisory/Consultancy: Seattle Genetics. B. Besse: Research grant/Funding (institution): AbbVie;Research grant/Funding (institution): Amgen;Research grant/Funding (institution): AstraZeneca;Research grant/Funding (institution): Beigene;Research grant/Funding (institution): Blueprint Medicine;Research grant/Funding (institution): BMS;Research grant/Funding (institution): Boehringer Ingelheim;Research grant/Funding (institution): Cellgene;Research grant/Funding (institution): Cristal Therapeutics;Research grant/Funding (institution): Daichi-Sankyo;Research grant/Funding (institution): Elli-Lilly;Research grant/Funding (institution): GSK;Research grant/Funding (institution): Ignyta;Research grant/Funding (institution): Ipsen;Research grant/Funding (institution): Inivata;Research grant/Funding (institution): Janssen;Research grant/Funding (institution): Merck KgaA;Research grant/Funding (institution): MSD;Research grant/Funding (institution): Nektar;Research grant/Funding (institution): Onxeo;Research grant/Funding (institution): Ose Immunotherapeutics;Research grant/Funding (institution): Pfizer;Research grant/Funding (institution): PharmaMar;Research grant/Funding (institution): Roche-Genentech;Research grant/Funding (institution): Sanofi;Research grant/Funding (institution): Servier;Research grant/Funding (institution): Spectrum Pharmaceuticals;Research grant/Funding (institution): Takeda;Research grant/Funding (institution): Tiziana Pharma;Research grant/Funding (institution): Tolero Pharmaceuticals. All other authors have declared no conflicts of interest.

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