A5038721807- Hepatocellular Carcinoma Treatment and Prognosis
- Cancer Immunotherapy and Biomarkers
- Liver Disease Diagnosis and Treatment
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Monoclonal and Polyclonal Antibodies Research
- Esophageal Cancer Research and Treatment
- Cancer Mechanisms and Therapy
- Pharmaceutical Practices and Patient Outcomes
- Gastrointestinal Tumor Research and Treatment
- Lung Cancer Treatments and Mutations
- Gastric Cancer Management and Outcomes
- HER2/EGFR in Cancer Research
- Liver physiology and pathology
- Pharmacogenetics and Drug Metabolism
- Pharmaceutical studies and practices
- Hepatitis C virus research
- Health Systems, Economic Evaluations, Quality of Life
- Hepatitis B Virus Studies
- Ferroptosis and cancer prognosis
- Economic and Financial Impacts of Cancer
- Patient Safety and Medication Errors
- Ethics in Clinical Research
- Cardiac Ischemia and Reperfusion
AstraZeneca (United States)
2018-2025
AstraZeneca (Japan)
2021-2024
AstraZeneca (Brazil)
2023
National Heart Lung and Blood Institute
2011-2014
Instituto Oncológico Henry Moore
2004-2009
Salk Institute for Biological Studies
2004-2006
Vollum Institute
2004
Oregon Health & Science University
2004
University of California, San Francisco
2004
University of Iowa
2004
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...
This phase I/II study evaluated tremelimumab (anticytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody) and durvalumab (antiprogrammed death ligand-1 as monotherapies in combination for patients with unresectable hepatocellular carcinoma (HCC), including a novel regimen featuring single, priming dose of (ClinicalTrials.gov identifier: NCT02519348).Patients HCC who had progressed on, were intolerant to, or refused sorafenib randomly assigned to receive T300 + D (tremelimumab 300 mg...
379 Background: A single priming dose of T (anti-CTLA-4) added to D (anti-PD-L1) in the STRIDE (Single Regular Interval D) regimen, formerly T300+D, showed encouraging clinical activity and limited toxicity a phase 2 uHCC study (Study 22, NCT02519348), suggesting exposure is sufficient improve upon activity. HIMALAYA (NCT03298451) evaluated efficacy safety or vs sorafenib (S) uHCC. Methods: an open-label, multicenter, 3 study, which pts with no prior systemic therapy were initially...
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...
Standard-of-care for resectable gastric/gastroesophageal junction cancer includes surgery and neoadjuvant-adjuvant 5-fluorouracil-leucovorin-oxaliplatin-docetaxel (FLOT) chemotherapy. Early-phase clinical studies support further development of the immune checkpoint inhibitor (ICI); durvalumab, an anti-PD-L1 antibody, in patients with cancer. Accumulating evidence indicates that ICIs combined FLOT chemotherapy improve outcomes advanced or metastatic We describe rationale design MATTERHORN, a...
4508 Background: The combination of dual immune checkpoint inhibitors (ICI) T (anti–CTLA-4) and D (anti–PD-L1) showed tolerability with a promising objective response rate (ORR) in the initial cohort this study (NCT02519348). Subsequent evaluation pts solid tumors treated increasing doses suggested priming higher dose may induce stronger enhance anti-tumor activity. Thus, randomized expansion cohorts comprised 4 arms evaluating as monotherapies 2 T+D regimens, including novel regimen...
TPS4144 Background: Thus far, sorafenib remains the standard of care for first line systemic therapy in patients with advanced HCC but patient prognosis and quality life (QOL) continues to be poor. may responsive immunotherapy due higher expression immunosuppressive cells upregulation CTLA-4 PD-1 immune checkpoints (Gao et al 2009, Hato 2014, Pardee & Butterfield 2012). Hepatitis B virus (HBV) hepatitis C (HCV) infection are also associated regulatory T PD-L1/PD-1 (Miroux 2010, Blockade or...
In the phase III HIMALAYA study (ClinicalTrials.gov identifier: NCT03298451) in unresectable hepatocellular carcinoma (uHCC), Single Tremelimumab Regular Interval Durvalumab (STRIDE) regimen significantly improved overall survival versus sorafenib, and durvalumab monotherapy was noninferior to sorafenib. Patient-reported outcomes (PROs), a secondary outcome from HIMALAYA, are reported here.
Highlights•The HIMALAYA study showed improved outcomes with STRIDE vs. sorafenib in unresectable hepatocellular carcinoma (uHCC).•In an Asian subgroup of HIMALAYA, overall survival and objective response rates sorafenib.•Outcomes were the participants enrolled Hong Kong Taiwan.•Treatment-related adverse events generally manageable low grade subgroup.•STRIDE is beneficial for people uHCC Asia-Pacific region, consistent global population.AbstractBackground & AimsIn global, phase III (uHCC),...
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).
TPS4151 Background: Gastric and gastroesophageal junction cancers (GC, GEJC) are the fifth most common cancer types third leading cause of cancer-related deaths globally (Globocan 2020). Standard care for resectable GC/GEJC includes neoadjuvant-adjuvant FLOT chemotherapy (5-fluorouracil + leucovorin oxaliplatin docetaxel) combined with surgery lymph node dissection some regions world. While treatment advances have improved survival, 5-year recurrence rate remains high overall survival (OS)...
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...
4004 Background: Immune checkpoint inhibitor (ICI) studies have shown an association between the occurrence of imAEs and outcomes. In Phase 3 HIMALAYA study (NCT03298451) in uHCC, STRIDE (Single T Regular Interval D) significantly improved overall survival (OS) vs sorafenib (S), D monotherapy was noninferior to S. had manageable safety (Abou-Alfa et al. NEJM Evid 2022). is approved for uHCC United States Japan recommended approval by European Medicines Agency; Japan. This exploratory...
erbB2/Her2, a ligandless receptor kinase, has pleiotropic effects on mammalian development and human disease. The absence of erbB2 signaling in cardiac myocytes results dilated cardiomyopathy mice, resembling the cardiotoxic observed subset breast cancer patients treated with anti-Her2 antibody herceptin. Emerging evidence suggests that is pivotal for integrating networks involving multiple classes extracellular signals. However, its role G protein-coupled (GPCR) remains undefined. Because...
TPS373 Background: Esophageal cancer is the eighth most common type and sixth leading cause of cancer-related death worldwide, esophageal squamous cell carcinoma (ESCC) cancer. For patients with locally advanced, unresectable ESCC (AJCC 8th Stage II–IVA), definitive chemoradiotherapy (dCRT) current standard care; however, up to half will experience disease progression within two years dCRT, overall survival rates remain suboptimal. The combination immune checkpoint inhibitors CRT has...
This study aimed to elucidate the patient experience of hepatocellular carcinoma (HCC) guide patient-centered outcome measurement in drug development.Patients with HCC participated qualitative interviews elicit disease-related signs/symptoms and impacts, using discussion guides developed from literature searches discussions oncologists. Interview participants rated disturbance their experiences (0-10 scale). A conceptual model was mapped against patient-reported (PRO) instruments identified...
4073 Background: In the Phase 3 HIMALAYA study (NCT03298451) in uHCC, STRIDE (Single T Regular Interval D) significantly improved overall survival versus sorafenib (S) and had manageable safety (Abou-Alfa et al. NEJM Evid 2022). is approved for uHCC United States Japan recommended approval by European Medicines Agency. this exploratory post hoc analysis, we assessed temporal patterns of imAEs regimen HIMALAYA. Methods: Safety was participants (pts) who received ≥1 dose (T 300 mg [one dose]...
The STRIDE (Single Tremelimumab Regular Interval Durvalumab) regimen of single-dose tremelimumab 300 mg, plus durvalumab 1,500 mg every 4 weeks demonstrated potential for long-term survival in studies unresectable hepatocellular carcinoma (uHCC; Study 22 and HIMALAYA). aim this analysis was to investigate changes proliferating CD4+ Ki67+ CD8+ T cells their relationship with exposure patients uHCC. Median cell count, change from baseline, percent baseline peaked around 14 days after STRIDE. A...
4022 Background: Study 22 (NCT02519348), a Phase 2 trial of immune checkpoint inhibitor (ICI) monotherapy and combination regimens in uHCC, showed higher rates objective response (ORR) with STRIDE (Single Tremelimumab [T] Regular Interval Durvalumab [D]) or D plus bevacizumab (B) than (1,2). Pharmacodynamic analyses that improved efficacy versus was associated increased expansion T cell clones at the end cycle 1 (C1) (3). We performed further clone to include D+B compared gene expression...