scholarly journals WEE1 Inhibitor: Clinical Development

2021 ◽  
Vol 23 (9) ◽  
Author(s):  
Anthony Kong ◽  
Hisham Mehanna
Keyword(s):  
Clinical Trials ◽  
Tp53 Mutation ◽  
Predictive Biomarker ◽  
Concurrent Chemotherapy ◽  
Clinical Development ◽  
Novel Agents ◽  
The Novel ◽  
Grade 3 ◽  
Chemotherapy Agents

Abstract Purpose of Review WEE1 inhibitor has been shown to potential chemotherapy or radiotherapy sensitivity in preclinical models, particularly in p53-mutated or deficient cancer cells although not exclusively. Here, we review the clinical development of WEE1 inhibitor in combination with chemotherapy or radiotherapy with concurrent chemotherapy as well as its combination with different novel agents. Recent Findings Although several clinical trials have shown that WEE1 inhibitor can be safely combined with different chemotherapy agents as well as radiotherapy with concurrent chemotherapy, its clinical development has been hampered by the higher rate of grade 3 toxicities when added to standard treatments. A few clinical trials had also been conducted to test WEE1 inhibitor using TP53 mutation as a predictive biomarker. However, TP53 mutation has not been shown to be the most reliable predictive biomarker and the benefit of adding WEE1 inhibitor to chemotherapy has been modest, even in TP53 biomarker-driven studies. Summary There are ongoing clinical trials testing WEE1 inhibitor with novel agents such as ATR and PAPR inhibitors as well as anti-PDL1 immunotherapy, which may better define the role of WEE1 inhibitor in the future if any of the novel treatment combination will show superior anti-tumor efficacy with a good safety profile compared to monotherapy and/or standard treatment.

scholarly journals The role of PD-L1 expression as a predictive biomarker in advanced renal cell carcinoma: A meta-analysis of randomized clinical trials

2019 ◽  
Vol 30 ◽  
pp. v40
Author(s):  
A. Carretero-Gonzalez ◽  
I. Martín Sobrino ◽  
I. Sáez Sanz ◽  
D. Castellano Gauna ◽  
G.A. De Velasco Oria de Rueda
Keyword(s):  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Predictive Biomarker ◽  
Advanced Renal Cell Carcinoma

scholarly journals Repurposing the estrogen receptor modulator raloxifene to treat SARS-CoV-2 infection

2021 ◽  
Author(s):  
Marcello Allegretti ◽  
Maria Candida Cesta ◽  
Mara Zippoli ◽  
Andrea Beccari ◽  
Carmine Talarico ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Estrogen Receptor ◽  
Early Stage ◽  
Clinical Development ◽  
Immune Memory ◽  
Therapeutic Drug ◽  
The Novel ◽  
Drug Candidates ◽  
Receptor Modulator ◽  
Attractive Candidate

AbstractThe ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitates strategies to identify prophylactic and therapeutic drug candidates to enter rapid clinical development. This is particularly true, given the uncertainty about the endurance of the immune memory induced by both previous infections or vaccines, and given the fact that the eradication of SARS-CoV-2 might be challenging to reach, given the attack rate of the virus, which would require unusually high protection by a vaccine. Here, we show how raloxifene, a selective estrogen receptor modulator with anti-inflammatory and antiviral properties, emerges as an attractive candidate entering clinical trials to test its efficacy in early-stage treatment COVID-19 patients.

scholarly journals The future of anti-CD20 monoclonal antibodies: are we making progress?

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 2993-3001 ◽  
Author(s):  
Waleed Alduaij ◽  
Tim M. Illidge
Keyword(s):  
Monoclonal Antibody ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Personalized Medicine ◽  
Clinical Development ◽  
The Novel ◽  
Next Generation ◽  
B Cell Malignancies ◽  
Clinical Community ◽  
Anti Cd20

AbstractThe anti-CD20 monoclonal antibody (mAb) rituximab has revolutionized the treatment of B-cell malignancies. This unprecedented success has not only substantially changed the mindset of the clinical community about the ability of mAb to improve outcomes but has catalyzed the interest in the pharmaceutical industry to develop the next generation of anti-CD20 mAbs. Since the introduction of rituximab 15 years ago, we have learned much about the potential mechanisms underlying the therapeutic efficacy of anti-CD20 mAbs. In parallel, many novel anti-CD20 mAbs have entered the clinic, each designed with modifications to structure aimed at further improving efficacy. On review of the newer generation of anti-CD20 mAbs entering clinical trials, it appears that the link between the novel mechanistic insights and the development of these next-generation anti-CD20 mAbs is unclear. As we move into an era of personalized medicine, it will become increasingly important for us to develop closer links between the emerging mechanistic insights and the clinical development, to further enhance the potency of anti-CD20 mAbs beyond that achieved with rituximab.

Maintenance Therapies for Multiple Myeloma (MM): A Direct Meta-Analysis

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4271-4271
Author(s):  
Helen Mahony ◽  
Ambuj Kumar ◽  
Rahul Mhaskar ◽  
Branko Miladinovic ◽  
Keith Wheatley ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Meta Analysis ◽  
Phase Iii ◽  
Novel Agents ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
The Novel ◽  
Significant Difference ◽  
American Society

Abstract Abstract 4271 Background: The role of various maintenance therapies in the management of MM is unclear and evidence on the efficacy of these regimens is conflicting. In order to provide the totality of available randomized evidence on the role of maintenance therapy in MM, we conduct a comprehensive systematic review and meta-analysis of all RCTs studying maintenance therapy. Here, we report the pooled results of trials which directly examined the novel agents of bortezomib, lenalidomide, or thalidomide and reported the outcomes of overall survival (OS) and/or progression-free survival (PFS). Methods: A comprehensive literature search of MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), and meetings abstracts from American Society of Hematology, American Society of Clinical Oncology, European Society for Medical Oncology and European Hematology Association was undertaken to identify all phase III randomized controlled trials (RCTs) of maintenance therapy published until July 2012. We extracted data on OS and PFS. Time to event data were pooled under the random effects model as hazard ratios (HR) and its corresponding 95% confidence interval (CI). Heterogeneity was assessed using the chi square test and I2statistic. All analyses were done in Review Manager 5.1. Results: Twenty-two RCTs met the inclusion criteria. (Figure 1) However, only data from the following RCTs were able to be pooled for the direct head-to-head comparison: 2 RCTs of bortezomib maintenance therapy enrolling 792 patients, 5 RCTs of lenalidomide maintenance therapy enrolling 1776 patients, 11 RCTs of thalidomide maintenance therapy enrolling 3952 patients. The pooled HR and 95% CI, number of RCTs, and number of patients for each comparison are presented in Figure 2. Only two trials compared the novel agents of bortezomib and thalidomide head-to-head. There was no significant different in terms of PFS. For the novel agent of lenalidomide, there was no significant difference is OS compared to placebo. The pooled PFS was in favor of lenalidomide maintenance compared to placebo. For thalidomide, OS was significantly in favor of the intervention when compared to placebo or prednisone/dexamethasone. There was no significant difference in OS between thalidomide maintenance when compared to interferon control. For the outcome of PFS, the pooled results favored thalidomide when compared to prednisone/dexamethasone or interferon control. There was no significant difference between thalidomide and placebo. Conclusion: To date, the largest number of trials has been among thalidomide as maintenance therapy. In our meta-analysis, thalidomide is the only agent which improves survival compared to no treatment. Other novel agents have been evaluated in a smaller number of trials and current data does not allow for firm conclusions that any agent is superior to the other. An indirect, network meta-analysis is called for to provide additional insights regarding comparative efficacy of the novel agents as the maintenance treatment for MM. Disclosures: No relevant conflicts of interest to declare.

Autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma (MM) in the era of novel agents: A meta-analysis of phase III randomized controlled trials.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8022-8022
Author(s):  
Binod Dhakal ◽  
Saurabh Chhabra ◽  
Mehdi Hamadani ◽  
Anita D'souza ◽  
Saad Zafar Usmani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Meta Analysis ◽  
Phase Iii ◽  
Novel Agents ◽  
High Dose ◽  
Significant Heterogeneity ◽  
Cell Transplant ◽  
The Novel ◽  
Novel Agent

8022 Background: Given the unprecedented deep response rates with the novel agent induction, the role of high dose therapy (HDT) followed by ASCT in MM pts. has been questioned, and was re-evaluated in a number of randomized clinical trials (RCTs). Although, the results of most studies suggest the continued benefit of HDT/ASCT, some RCTs suggest no overall survival (OS) benefit. We undertook a systematic review and meta-analysis of phase III randomized RCTs evaluating the role of HDT compared to standard therapy (SDT) in the context of novel agent induction Methods: We searched the PubMed, Scopus and Cochrane Collection of Controlled Trial databases using the term myeloma combined with autologous or transplant or myeloablative or stem cell from 2000-2016. A total of 2480 articles identified, of which 4 large phase III RCTs compared upfront HDT with SDT with novel agents use. Two individuals independently extracted the data. Reported hazard ratio (HR) and survival data were pooled using random effects models (STATA v14, College Station, Tx). Heterogeneity was assessed using I2. Results: Four studies comprising 2421 patients were included (Table 1). One study did not report the HR for death and hence OS analysis was limited to 3 studies. The combined hazard for progression with HDT was 0.55 (95% CI 0.40-0.71) (p < 0.005). The combined hazard for death with HDT was 0.65 (95% CI 0.29-1.0) (p = 0.007). Sensitivity and sub-group analysis showed no difference in PFS (p = 0.06) and OS (p = 0.22) with HDT. Significant heterogeneity was demonstrated by I2 of 71.4% for PFS (p = 0.01) and 68.4% for OS (p = 0.04). Conclusions: Based on our analysis, even in the novel agent era, HDT appears to be beneficial and should be considered standard of care for all transplant eligible MM pts. [Table: see text]

ASCT for Multiple Myeloma: The Role of the Novel Agents

2014 ◽  
Vol 14 (55) ◽  
pp. 31-33
Author(s):  
E. Hitt Nichols ◽  
J. Mikhael ◽  
P. G. Richardson ◽  
P. Moreau
Keyword(s):  
Multiple Myeloma ◽  
Novel Agents ◽  
The Novel

scholarly journals An Update on the Leading COVID-19 Vaccines

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Ahmed Eladely ◽  
Keyword(s):  
Clinical Trials ◽  
Vaccine Efficacy ◽  
Vaccine Development ◽  
Vaccine Safety ◽  
Clinical Development ◽  
Phase Iii ◽  
Phase Iii Clinical Trials

We reviewed the COVID-19 vaccines that reached phase III of clinical development. For each of the 10 vaccines identified, we described the technology used for vaccine development, the available data from phase III clinical trials, data on vaccine safety, and the role of new SARS-CoV-2 variants on vaccine efficacy.

New therapeutic strategies regarding endovascular treatment of glioblastoma, the role of the blood–brain barrier and new ways to bypass it

2015 ◽  
Vol 8 (10) ◽  
pp. 1078-1082 ◽  
Author(s):  
S Peschillo ◽  
A Caporlingua ◽  
F Diana ◽  
F Caporlingua ◽  
R Delfini
Keyword(s):  
Clinical Trials ◽  
Endovascular Treatment ◽  
Blood Brain Barrier ◽  
New Technologies ◽  
Brain Barrier ◽  
Treatment Protocols ◽  
Innovative Methods ◽  
Blood Brain ◽  
Chemotherapy Agents

The treatment protocols for glioblastoma multiforme (GBM) involve a combination of surgery, radiotherapy and adjuvant chemotherapy. Despite this multimodal approach, the prognosis of patients with GBM remains poor and there is an urgent need to develop novel strategies to improve quality of life and survival in this population. In an effort to improve outcomes, intra-arterial drug delivery has been used in many recent clinical trials; however, their results have been conflicting. The blood–brain barrier (BBB) is the major obstacle preventing adequate concentrations of chemotherapy agents being reached in tumor tissue, regardless of the method of delivering the drugs. Therapeutic failures have often been attributed to an inability of drugs to cross the BBB. However, during the last decade, a better understanding of BBB physiology along with the development of new technologies has led to innovative methods to circumvent this barrier. This paper focuses on strategies and techniques used to bypass the BBB already tested in clinical trials in humans and also those in their preclinical stage. We also discuss future therapeutic scenarios, including endovascular treatment combined with BBB disruption techniques, for patients with GBM.

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