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https://www.readbyqxmd.com/read/28723489/immunotherapy-for-renal-cancer-sequencing-and-combinations
#1
REVIEW
Grant D Stewart, Maria De Santis, Bernard Escudier, Thomas Powles, Guru Sonpavde
CONTEXT: Current therapy for renal cell carcinoma (RCC) generally consists of the sequential administration of single agent therapy. Given the advent of T-cell checkpoint inhibitors, the role of combinations including these agents is being intensely interrogated. OBJECTIVE: To evaluate ongoing trials of combinations including immunotherapy and sequencing of agents to treat RCC. EVIDENCE ACQUISITION: Recent data and ongoing trials were analyzed to evaluate the direction of research in this arena...
December 15, 2016: European Urology Focus
https://www.readbyqxmd.com/read/28717238/molecular-mechanism-of-pd-1-pd-l1-blockade-via-anti-pd-l1-antibodies-atezolizumab-and-durvalumab
#2
Hyun Tae Lee, Ju Yeon Lee, Heejin Lim, Sang Hyung Lee, Yu Jeong Moon, Hyo Jeong Pyo, Seong Eon Ryu, Woori Shin, Yong-Seok Heo
In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, durvalumab, and avelumab, were approved by the FDA for the treatment of multiple advanced cancers. And many other anti-PD-L1 antibodies are under clinical trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and avelumab have been determined, revealing details of the antigen-antibody interactions. However, it is still unknown how atezolizumab and durvalumab specifically recognize PD-L1, although this is important for investigating novel binding sites on PD-L1 targeted by other therapeutic antibodies for the design and improvement of anti-PD-L1 agents...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705024/medi-4736-durvalumab-in-non-small-cell-lung-cancer
#3
Arnaud Jeanson, Fabrice Barlesi
Immune checkpoint inhibitors (ICI) are now a therapeutic option for advanced non-small cell lung cancer (NSCLC) patients. ICI, such as the PD-1 inhibitors nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab, have already been marketed for the treatment of pretreated patients with advanced NSCLC. Other notable PD-L1 inhibitors under development include avelumab and durvalumab. Areas covered: This article reviews literature on durvalumab development, from the preclinical data to the results of phase III clinical trials, whether published or presented at international scientific conferences...
July 13, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28699934/in-brief-avelumab-bavencio-for-metastatic-merkel-cell-carcinoma
#4
(no author information available yet)
No abstract text is available yet for this article.
July 17, 2017: Medical Letter on Drugs and Therapeutics
https://www.readbyqxmd.com/read/28679778/combination-therapy-with-nhs-muil12-and-avelumab-anti-pd-l1-enhances-antitumor-efficacy-in-preclinical-cancer-models
#5
Chunxiao Xu, Yanping Zhang, P Alexander Rolfe, Vivian M Hernández, Wilson Guzman, Giorgio Kradjian, Bo Marelli, Guozhong Qin, Jin Qi, Hong Wang, Huakui Yu, Robert Tighe, Kin-Ming Lo, Jessie M English, Laszlo G Radvanyi, Yan Lan
To determine if combination therapy with NHS-muIL12 and the anti-PD-L1 antibody avelumab can enhance anti-tumor efficacy in preclinical models relative to monotherapies.<br /><br />Experimental Design: BALB/c mice bearing orthotopic EMT-6 mammary tumors and μMt(-) mice bearing subcutaneous MC38 tumors were treated with NHS-muIL12, avelumab, or combination therapy; tumor growth and survival were assessed. Tumor recurrence following remission and rechallenge was evaluated in EMT-6 tumor-bearing mice...
July 5, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28585617/-immunotherapy-for-lung-cancer
#6
Gyula Ostoros
Similarly to other malignancies, immune checkpoint inhibitor therapy is a revolutionary, effective new treatment possibility for lung cancer. In lung cancer carcinogenesis is related mainly to tobacco smoking with high somatic mutation rate and immunogenicity. The PD-1 inhibitor nivolumab and pembrolizumab and the PD-L1 inhibitor atezolizumab is a labelled indication in second line setting in advanced nonsmall cell lung cancer (NSCLC). Avelumab and durvalumab have promising activity as well. Based on the data of KEYNOTE 024 trial, pembrolizumab is approved in first line setting for cases with ≥50% PD-L1 expression...
June 6, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28585615/-the-role-of-immunotherapy-in-the-modern-treatment-of-urothelial-carcinoma
#7
Anikó Maráz, Lajos Géczi
By the emergence of modern immunotherapies with active agents like PD-1 (nivolumab, pembrolizumab) and PD-L1 immune checkpoint blockers (atezolizumab, avelumab, durvalumab), new therapeutic options have become available for the treatment of patients with locally advanced and metastatic urothelial carcinoma. According to the recent publications, they have been effective in case of progression after platinum therapy, in or after second-line and in firstline therapies for cisplatin ineligible patients, respectively...
June 6, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28579722/pharmaceutical-approval-update
#8
Mary Choy
Ribociclib (Kisqali) for HR+/HER2- advanced or metastatic breast cancer in postmenopausal women; safinamide (Xadago) as adjunctive treatment for patients with Parkinson's disease; and avelumab (Bavencio) for metastatic Merkel cell carcinoma.
June 2017: P & T: a Peer-reviewed Journal for Formulary Management
https://www.readbyqxmd.com/read/28546286/three-drugs-approved-for-urothelial-carcinoma-by-fda
#9
(no author information available yet)
The FDA has approved one PD-1 checkpoint inhibitor, pembrolizumab, and two PD-L1 checkpoint inhibitors, avelumab and durvalumab, to treat metastatic urothelial carcinoma in patients whose disease continues to progress despite platinum-based chemotherapy. This brings the total number of checkpoint inhibitors for the disease to five, prompting questions about how best to use them.
May 25, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28499515/incidence-of-pneumonitis-with-use-of-programmed%C3%A2-death-1-and-programmed-death-ligand-1-inhibitors%C3%A2-in%C3%A2-non-small-cell%C3%A2-lung%C3%A2-cancer-a-systematic-review-and-meta-analysis-of-trials
#10
Monica Khunger, Sagar Rakshit, Vinay Pasupuleti, Adrian V Hernandez, Peter Mazzone, James Stevenson, Nathan A Pennell, Vamsidhar Velcheti
BACKGROUND: Programmed death 1 (PD-1) programmed death-ligand 1 (PD-L1) inhibitors show significant clinical activity in non-small cell lung carcinoma (NSCLC). However, they are often associated with potentially fatal immune-mediated pneumonitis. Preliminary reports of trials suggest a difference in the rate of pneumonitis with PD-1 and PD-L1 inhibitors. We sought to determine the overall incidence of pneumonitis and differences according to type of inhibitors and prior chemotherapy use...
August 2017: Chest
https://www.readbyqxmd.com/read/28493171/immunotherapy-in-urothelial-cancer-recent-results-and-future-perspectives
#11
REVIEW
Matthew S Farina, Kevin T Lundgren, Joaquim Bellmunt
Cytotoxic chemotherapy has been the only systemic treatment of locally advanced and metastatic urothelial carcinoma for decades. Long-term survival remains stagnant around 12-14 months for patients with advanced disease who have progressed on or recurred after receiving first-line platinum-based chemotherapy. Improving clinical outcomes for patients with urothelial carcinoma in all disease settings requires the development of novel treatments, especially for patients who failed on first-line chemotherapy. Since the discovery of intravesical Bacillus-Calmette Guerin (BCG) in the 1970s for non-muscle invasive disease, there have not been any major breakthrough drugs that exploit the immune-sensitivity of bladder cancer until recently...
July 2017: Drugs
https://www.readbyqxmd.com/read/28477372/adcc-employing-an-nk-cell-line-hank-expressing-the-high-affinity-cd16-allele-with-avelumab-an-anti-pd-l1-antibody
#12
Caroline Jochems, James W Hodge, Massimo Fantini, Kwong Y Tsang, Amanda J Vandeveer, James L Gulley, Jeffrey Schlom
NK-92 cells, and their derivative, designated aNK, were obtained from a patient with non-Hodgkin lymphoma. Prior clinical studies employing adoptively transferred irradiated aNK cells have provided evidence of clinical benefit and an acceptable safety profile. aNK cells have now been engineered to express IL-2 and the high affinity (ha) CD16 allele (designated haNK). Avelumab is a human IgG1 anti-PD-L1 monoclonal antibody, which has shown evidence of clinical activity in a range of human tumors. Prior in vitro studies have shown that avelumab has the ability to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) of human tumor cells when combined with NK cells...
May 6, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28456944/avelumab-first-global-approval
#13
Esther S Kim
Avelumab (Bavencio(®)) is an intravenously administered programmed cell death ligand-1-blocking human antibody initially developed by EMD Serono Inc. (the biopharmaceutical division of Merck KGaA, Darmstadt, Germany) [now jointly developed and commercialized by EMD Serono Inc. and Pfizer] for the treatment of various tumours. It has received accelerated approval in the USA for the treatment of metastatic Merkel cell carcinoma (mMCC) in adults and paediatric patients aged ≥12 years. The marketing authorization application for avelumab in the treatment of mMCC is undergoing regulatory review in the EU, the biologics license application for avelumab in the treatment of urothelial carcinoma is undergoing priority review by the FDA, and avelumab is in various stages of development internationally for a variety of cancers...
May 2017: Drugs
https://www.readbyqxmd.com/read/28438774/avelumab-impresses-in-merkel-cell-carcinoma
#14
(no author information available yet)
The PD-L1 inhibitor avelumab-approved by the FDA in March for the treatment of Merkel cell carcinoma-demonstrated a high number of durable responses in an international, open-label, prospective phase II study. The results of the study, which supported the FDA's decision, were presented in April at the American Association for Cancer Research (AACR) Annual Meeting 2017.
June 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28423552/enhanced-antitumor-effects-by-combining-an-il-12-anti-dna-fusion-protein-with-avelumab-an-anti-pd-l1-antibody
#15
Jonathan K Fallon, Amanda J Vandeveer, Jeffrey Schlom, John W Greiner
The combined therapeutic potential of an immunocytokine designed to deliver IL-12 to the necrotic regions of solid tumors with an anti-PD-L1 antibody that disrupts the immunosuppressive PD-1/PD-L1 axis yielded a combinatorial benefit in multiple murine tumor models. The murine version of the immunocytokine, NHS-muIL12, consists of an antibody (NHS76) recognizing DNA/DNA-histone complexes, fused with two molecules of murine IL-12 (NHS-muIL12). By its recognition of exposed DNA, NHS-muIL12 targets IL-12 to the necrotic portions of tumors; it has a longer plasma half-life and better antitumor efficacy against murine tumors than recombinant murine IL-12...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28407031/avelumab-clinical-trial-innovation-and-collaboration-to-advance-anti-pd-l1-immunotherapy
#16
K Chin, V K Chand, D S A Nuyten
No abstract text is available yet for this article.
April 12, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28403786/immune-checkpoint-inhibitors-and-cardiac-toxicity-an-emerging-issue
#17
Gilda Varricchi, Giancarlo Marone, Valentina Mercurio, Maria Rosaria Galdiero, Domenico Bonaduce, Carlo G Tocchetti
Although survival of patients with different types of cancer has improved, cardiotoxicity induced by anti-neoplastic drugs remains a critical issue. Cardiac dysfunction after treatment with anthracyclines has historically been a major problem. However, also targeted therapies and biological molecules can induce reversible and irreversible cardiac dysfunction. Cancer immunotherapies over the last years have revolutionized the clinical management of a wide spectrum of solid and hematopoietic malignancies previously endowed with poor prognosis...
April 7, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28375787/avelumab-an-anti-programmed-death-ligand-1-antibody-in-patients-with-refractory-metastatic-urothelial-carcinoma-results-from-a-multicenter-phase-ib-study
#18
Andrea B Apolo, Jeffrey R Infante, Ani Balmanoukian, Manish R Patel, Ding Wang, Karen Kelly, Anthony E Mega, Carolyn D Britten, Alain Ravaud, Alain C Mita, Howard Safran, Thomas E Stinchcombe, Marko Srdanov, Arnold B Gelb, Michael Schlichting, Kevin Chin, James L Gulley
Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1...
July 1, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28373007/avelumab-for-metastatic-or-locally-advanced-previously-treated-solid-tumours-javelin-solid-tumor-a-phase-1a-multicohort-dose-escalation-trial
#19
Christopher R Heery, Geraldine O'Sullivan-Coyne, Ravi A Madan, Lisa Cordes, Arun Rajan, Myrna Rauckhorst, Elizabeth Lamping, Israel Oyelakin, Jennifer L Marté, Lauren M Lepone, Renee N Donahue, Italia Grenga, Jean-Marie Cuillerot, Berend Neuteboom, Anja von Heydebreck, Kevin Chin, Jeffrey Schlom, James L Gulley
BACKGROUND: Avelumab (MSB0010718C) is a human IgG1 monoclonal antibody that binds to PD-L1, inhibiting its binding to PD-1, which inactivates T cells. We aimed to establish the safety and pharmacokinetics of avelumab in patients with solid tumours while assessing biological correlatives for future development. METHODS: This open-label, single-centre, phase 1a, dose-escalation trial (part of the JAVELIN Solid Tumor trial) assessed four doses of avelumab (1 mg/kg, 3 mg/kg, 10 mg/kg, and 20 mg/kg), with dose-level cohort expansions to provide additional safety, pharmacokinetics, and target occupancy data...
May 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28373006/avelumab-an-anti-pd-l1-monoclonal-antibody-shows-activity-in-various-tumour-types
#20
Athanasios Kotsakis, Vassilis Georgoulias
No abstract text is available yet for this article.
May 2017: Lancet Oncology
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