Search results for "Durvalumab"
showing 10 items of 13 documents
Phase Ib/II trial evaluating the safety, tolerability and immunological activity of durvalumab (MEDI4736) (anti-PD-L1) plus tremelimumab (anti-CTLA-4…
2018
Background 5-Fluorouracil plus irinotecan or oxaliplatin alone or in association with target therapy are standard first-line therapy for metastatic colorectal cancer (mCRC). Checkpoint inhibitors targeting PD-1/PD-L1 demonstrated efficacy on mCRC with microsatellite instability but remain ineffective alone in microsatellite stable tumour. 5-Fluorouracil and oxaliplatin were known to present immunogenic properties. Durvalumab (D) is a human monoclonal antibody (mAb) that inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor. Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This study is designed to evaluate whether the …
Immuno-oncology in GI tumours: Clinical evidence and emerging trials of PD-1/PD-L1 antagonists.
2018
The use of immune checkpoint inhibitors constitutes an emerging therapeutic field for the therapy of gastrointestinal (GI) malignancies following the recent FDA approvals of PD-1 inhibitors for esophago-gastric adenocarcinoma, hepatocellular carcinoma and for microsatellite-instable tumors, which are mainly colorectal cancers. This paper reviews the clinical evidence end of 2017 and discusses the clinical development programs of atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab in GI-tract cancers. Since 2014, these antagonists of the PD-1/PD-L1 axis have gained approval for use in numerous other tumors. Phase II trials and phase I expansion cohorts demonstrate clinical activi…
Evolution of checkpoint inhibitors for the treatment of metastatic gastric cancers: Current status and future perspectives.
2018
Abstract Background Standard treatment options for patients with advanced gastric or gastroesophageal junction cancer (GC/GEJC) are associated with limited efficacy and some toxicity. Recently, immunotherapy with antibodies that inhibit the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) interaction has emerged as a new treatment option. This manuscript reviews early-phase and late-phase trials of immunotherapy in advanced GC/GEJC. Methods Searches for studies of immunotherapy in GC/GEJC were performed using PubMed, ClinicalTrials.gov, and abstract databases for select annual congresses. Findings were interpreted based on expert opinion. Results Monotherapy with anti–PD-1/PD-L1 …
Promises and Pitfalls in the Use of PD-1/PD-L1 Inhibitors in Multiple Myeloma
2018
In the biology of multiple myeloma (MM), immune dysregulation has emerged as a critical component for novel therapeutic strategies. This dysfunction is due to a reduced antigen presentation, a reduced effector cell ability and a loss of reactive T cells against myeloma, together with a bone marrow microenvironment that favors immune escape. The Programmed Death-1 (PD-1) pathway is associated with the regulation of T cell activation and with the apoptotic pathways of effector memory T cells. Specifically, the binding with PD-1 ligand (PD-L1) on the surface of tumor plasma cells down-regulates T cell-proliferation, thus contributing to the immune escape of tumor cells. In relapsed and/or refr…
Immune-Related Pneumonitis After Chemoradiotherapy and Subsequent Immune Checkpoint Blockade in Unresectable Stage III Non-Small-Cell Lung Cancer.
2019
Approximately one third of patients with non-small-cell lung cancer (NSCLC) present with stage III or locally advanced NSCLC. These patients have historically been managed with chemoradiotherapy. However, outcomes for these patients remain poor, with a 5-year survival rate between 15% and 32%. Immune checkpoint inhibitors have revolutionized the treatment of patients with NSCLC. One such agent, durvalumab, a selective high-affinity human immunoglobulin G1 monoclonal antibody that blocks programmed cell death ligand 1 binding to programmed cell death protein 1 and cluster of differentiation 80, was recently approved in the consolidation setting after completion of definitive platinum-based c…
Durvalumab after definitive chemoradiotherapy in locally advanced unresectable non-small cell lung cancer (NSCLC): Real-world data on survival and sa…
2020
Abstract Background Following the PACIFIC trial, durvalumab has been approved by the European Medicines Agency (EMA) for consolidation of locally advanced PD-L1-positive NSCLC after chemoradiotherapy (CRT). Patients were treated with durvalumab in the EAP from 22.11.2017 to 15.10.2018 allowing analysis of its efficacy and safety. Methods Data from 56 centres were analysed for adverse events (AE), progression-free survival (PFS), overall survival (OS). Results 126 patients actually received at least 1 cycle durvalumab. Compared to the PACIFIC trial, the EAP population had more advanced stage and included “oligometastatic” stage IV patients and patients with autoimmune disease. PFS (20.1 mont…
In the literature: October 2020.
2020
Immune checkpoint inhibitors are widely used as treatment for an increasing number of solid tumours. Nevertheless, the lack of predictive biomarker represents a limitation across several cancer types. During the last years, the possibility to dynamically study tumour evolution through circulating tumour DNA (ctDNA) in plasma has opened novel possibility in evaluating disease status and therapeutic response, especially in localised disease to predict the possibility of relapse. However, the specific opportunities for application in the context of immunotherapy remain to be clarified.1 In an article recently published in Cancer Discovery by Zhang et al ,2 a comprehensive analysis of ctDNA dat…
PRODIGE 59-DURIGAST trial: A randomised phase II study evaluating FOLFIRI + Durvalumab ± Tremelimumab in second-line of patients with advanced gastri…
2021
International audience; Gastric or gastro-oesophageal junction (GEJ) adenocarcinomas present poor overall survival (OS). First-line chemotherapy regimen for patients with HER2-negative tumours is based on a doublet or triplet of fluoropyrimidine plus platinum salt ± taxane. Second-line chemotherapy (Docetaxel or Irinotecan) improves OS which nonetheless remains poor (around 5 months). The first results of immune checkpoint inhibitors (anti-PD-1) combined with chemotherapy in metastatic gastric and GEJ cancers were discordant in recent phase III trials. Data on dual-blockade (anti-PD-L1 or anti-PD-1 plus anti-CTLA-4) plus chemotherapy are lacking. DURIGAST is a randomised, multicenter, non-c…
Durvalumab after definitive chemoradiotherapy in locally advanced NSCLC: Data of the German EAP
2021
Following the PACIFIC trial, durvalumab has been approved by the European Medicines Agency (EMA) for consolidation of locally advanced PD-L1-positive NSCLC after chemoradiotherapy (CRT). Patients were treated with durvalumab in the EAP from 22.11.2017 to 15.10.2018 allowing analysis of its efficacy and safety. 211 patients were registered by 90 German centres. Data were collected retrospectively by questionnaire and queries. 56 centres reported data on 126 patients who actually received at least one cycle of durvalumab. In contrast to the PACIFIC-trial population, some patients with oligometastatic disease and a history of autoimmune disease are included in the EAP population. Information o…
Role of Immunotherapy in the Management of Hepatocellular Carcinoma: Current Standards and Future Directions
2020
The multikinase inhibitor sorafenib was the only approved systemic therapy in advanced hepatocellular carcinoma (HCC) for about a decade. In recent years, the number of approved agents has increased significantly as a result of a number of positive phase iii clinical trials. Lenvatinib as a first-line treatment, and regorafenib, cabozantinib, and ramucirumab in the second-line setting are now approved by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency. In phase II studies, immunotherapy with nivolumab and monotherapy using pembrolizumab yielded impressive results for overall survival in therapy-naïve and pretreated patients, leading to the accelerated approval …