A5048077180- Cancer Immunotherapy and Biomarkers
- Renal cell carcinoma treatment
- Hepatocellular Carcinoma Treatment and Prognosis
- Histone Deacetylase Inhibitors Research
- Protein Degradation and Inhibitors
- Signaling Pathways in Disease
- Pancreatic and Hepatic Oncology Research
- Colorectal Cancer Treatments and Studies
- CAR-T cell therapy research
- Mathematical Biology Tumor Growth
- NF-κB Signaling Pathways
- Liver Disease Diagnosis and Treatment
- Gastric Cancer Management and Outcomes
- Ubiquitin and proteasome pathways
- Bladder and Urothelial Cancer Treatments
- Cell death mechanisms and regulation
- Esophageal Cancer Research and Treatment
- Cancer Genomics and Diagnostics
- Natural product bioactivities and synthesis
- Cancer Mechanisms and Therapy
- Ferroptosis and cancer prognosis
- Lung Cancer Treatments and Mutations
- Peptidase Inhibition and Analysis
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Immune Cell Function and Interaction
AstraZeneca (United States)
2021-2025
AstraZeneca (Japan)
2022-2024
AstraZeneca (United Kingdom)
2024
AstraZeneca (Brazil)
2022
Bristol-Myers Squibb (United States)
2011-2016
Bristol-Myers Squibb (Germany)
2014-2016
Sarah Cannon Research Institute
2016
Angeles Clinic and Research Institute
2016
Huntsman Cancer Institute
2016
Institut Gustave Roussy
2016
BackgroundA single, high priming dose of tremelimumab (anti-cytotoxic T lymphocyte–associated antigen 4) plus durvalumab (anti–programmed cell death ligand-1), an infusion regimen termed STRIDE (Single Tremelimumab Regular Interval Durvalumab), showed encouraging clinical activity and safety in a phase 2 trial unresectable hepatocellular carcinoma.MethodsIn this global, open-label, 3 trial, the majority patients we enrolled with carcinoma no previous systemic treatment were randomly assigned...
To investigate the safety and efficacy of durvalumab, a human monoclonal antibody that binds programmed cell death ligand-1 (PD-L1), role PD-L1 expression on clinical response in patients with advanced urothelial bladder cancer (UBC).
BACKGROUND: Patients with advanced biliary tract cancer have a poor prognosis, and first-line standard of care (gemcitabine plus cisplatin) has remained unchanged for more than 10 years. The TOPAZ-1 trial evaluated durvalumab chemotherapy patients cancer. METHODS: In this double-blind, placebo-controlled, phase 3 study, we randomly assigned previously untreated unresectable or metastatic recurrent disease 1:1 to receive placebo in combination gemcitabine cisplatin up eight cycles, followed...
Abstract Purpose: Histone deacetylase (HDAC) inhibitors have emerged recently as promising anticancer agents. They arrest cells in the cell cycle and induce differentiation death. The antitumor activity of HDAC has been linked to their ability gene expression through acetylation histone nonhistone proteins. However, it suggested that may also enhance other cancer therapeutics, including radiotherapy. purpose this study was evaluate radiosensitize human melanoma vitro. Experimental Design: A...
Abstract Purpose: Nivolumab, an anti-PD-1 immune checkpoint inhibitor, improved overall survival versus everolimus in a phase 3 trial of previously treated patients with metastatic renal cell carcinoma (mRCC). We investigated immunomodulatory activity nivolumab hypothesis-generating prospective mRCC trial. Experimental Design: Nivolumab was administered intravenously every weeks at 0.3, 2, or 10 mg/kg to and treatment-naïve mRCC. Baseline on-treatment biopsies blood were obtained. Clinical...
5010 Background: Antiangiogenic agents sunitinib (S) and pazopanib (P) are SOC for mRCC, but new therapies needed as pts advance through therapy with limited survival benefit. We report preliminary results of a phase I trial nivolumab, fully human IgG4 PD-1 immune checkpoint inhibitor antibody, in combination S or P mRCC. Methods: mRCC patients (≥1 prior systemic therapy) received nivolumab (50 mg, 4 wks on, 2 off; arm S) (800 mg daily; P), until progression/unacceptable toxicity. Starting...
BackgroundIn the phase III HIMALAYA study (NCT03298451) in unresectable hepatocellular carcinoma (uHCC), STRIDE (Single Tremelimumab Regular Interval Durvalumab) significantly improved overall survival (OS) versus sorafenib; durvalumab monotherapy was noninferior to sorafenib for OS. Results reported herein are from a four-year updated OS analysis of HIMALAYA.Patients and methodsParticipants with uHCC no previous systemic treatment were randomized (n=393), (n=389), or (n=389). The data...
Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) have a poor prognosis. The phase III KESTREL study evaluated the efficacy of durvalumab [programmed death-ligand 1 (PD-L1) antibody] without tremelimumab [cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody], versus EXTREME regimen in patients R/M HNSCC.
LBA246 Background: FLOT was established as a perioperative therapy for GC/GEJC following the Phase 2/3 FLOT4 study conducted in Germany, with pCR rate of 16% (Al-Batran et al, Lancet Oncol 2016). The global MATTERHORN (NCT04592913) showed statistically significant improvement D + vs placebo (P) at first interim analysis (Janjigian ESMO Congress 2023). Subgroup analyses by region and country were completed to assess rates benefit across population. Methods: Participants (pts) resectable...
4504 Background: There is a need for agents that result in durable responses and improved tolerability patients (pts) with mRCC. Nivolumab, fully human IgG4 programmed death-1 (PD-1) immune checkpoint inhibitor antibody, has shown activity Combining nivolumab + ipilimumab, monoclonal antibody to CTLA-4, showed encouraging clinical acceptable safety advanced melanoma. We report preliminary results of the combination Methods: Pts mRCC (favorable/intermediate MSKCC score; Karnofsky performance...
Myc is a transcription factor that features prominently in cancer. The oncogenicity of stems from its ability to regulate expression genes required for cell growth and proliferation. Although the mechanisms through which activates have been extensively studied, less known about how represses transcription. Recently, we reported conserved element within Myc-MbIII- important transcriptional repression. Here, investigate mechanism MbIII contributes We show target Id2 Gadd153 by process involves...
The bcl-2 proto-oncogene is frequently expressed in human cancer. Although was first cloned as the t(14;18) translocation breakpoint from follicular B-cell lymphoma, it has become apparent that many cell types express because of transcriptional regulation. As such, several transcription factors have been demonstrated to activate expression bcl-2, including NF-kappaB. We investigated role NF-kappaB1 (p50) homodimers Bcl-2 two murine lymphoma lines: LY-as, an apoptosis-proficient line with low...
5012 Background: Nivolumab, a fully human IgG4 programmed death-1 (PD-1) inhibitor antibody, has shown encouraging activity in mRCC. This trial assessed the immunomodulatory and clinical activity, safety of nivolumab patients (pts) with Methods: Ninety-one pts received IV Q3W: pretreated (1–3 prior therapies; ≥1 anti-angiogenic agent) 0.3 (n=22), 2 or 10 mg/kg (n=23); 24 treatment-naïve mg/kg. Fresh biopsies serum were obtained at baseline (BL) cycle day 8 (C2D8; biopsy) 4 1 (C4D1; serum)....
A novel single-dose regimen of 300 mg tremelimumab in combination with durvalumab [Single Tremelimumab Regular Interval Durvalumab (STRIDE)] has demonstrated a favorable benefit-risk profile the phase I/II Study 22 (NCT02519348) and III HIMALAYA study (NCT03298451). This evaluated pharmacokinetics, exposure-response, exposure-pharmacodynamics relationships patients unresectable hepatocellular carcinoma (uHCC).
9029 Background: The PD-1/PD-L1 axis is an important immune inhibitory pathway contributing to tumor cell escape from immunosurveillance. A Phase 1/2 dose escalation and expansion study ongoing evaluate the safety efficacy of durvalumab, a modified human IgG1 mAb that blocks PD-L1 binding PD-1 CD80, in patients with advanced non‒small-cell lung cancer (NSCLC) or other solid types. Methods: Durvalumab 10 mg/kg given q2w for up 12 months treatment-naïve histologically cytologically documented...
What is this summary about? This a of results from phase 3 clinical study called HIMALAYA. HIMALAYA looked at treatment with one dose medication tremelimumab combined multiple doses durvalumab (the STRIDE regimen) or alone. These treatments were compared sorafenib in participants unresectable hepatocellular carcinoma (HCC). HCC type liver cancer that difficult to treat because it often diagnosed when unresectable, meaning can no longer be removed surgery. Sorafenib has been the main for...
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in several human tumors both vitro and vivo, however, some remain resistant for poorly understood reasons. Using a quantitative DNA fragmentation assay apoptosis, we have shown that prostate cancer cells are to wide range of TRAIL doses up 500 ng/ml. However, translation inhibitors, such as anisomycin, cycloheximide, emetine, harringtonine, puromycin, unlike transcription significantly sensitized PC3-neomycin...
In a previously published report (Kurland, J. F., Kodym, R., Story, M. D., Spurgers, K. B., McDonnell, T. J., and Meyn, R. E. (2001) Biol. Chem. 276, 45380–45386), we described the NFκB status for two murine B-cell lymphoma cell lines, LY-as (apoptosis-sensitive) LY-ar (apoptosis-refractory) provided evidence that NFκB1 (p50) homodimers contribute to expression of Bcl-2 in line. present study, investigated upstream signals leading p50 homodimer activation expression. We found cells, ERK1...
Abstract Melanoma tumors and cultured cell lines are relatively resistant to the cytotoxic effects of ionizing radiation, thereby limiting use radiotherapy for clinical treatment melanoma. New strategies sensitizing melanoma cells therefore deserve examination. In an attempt identify target signaling pathways that contribute radioresistance, we investigated role nuclear factor-κB (NF-κB), a transcription factor known inhibit apoptosis induced by variety stimuli promote radioresistance. Two...