Adnan Nagrial
A5070415176- Pancreatic and Hepatic Oncology Research
- Cancer Immunotherapy and Biomarkers
- Cancer Genomics and Diagnostics
- Neuroendocrine Tumor Research Advances
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Cancer Research and Treatments
- Colorectal Cancer Treatments and Studies
- Cancer, Hypoxia, and Metabolism
- Melanoma and MAPK Pathways
- Peptidase Inhibition and Analysis
- Radiomics and Machine Learning in Medical Imaging
- Cancer Cells and Metastasis
- Lung Cancer Diagnosis and Treatment
- Radiopharmaceutical Chemistry and Applications
- CAR-T cell therapy research
- Genetic factors in colorectal cancer
- Renal cell carcinoma treatment
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Hepatocellular Carcinoma Treatment and Prognosis
- Neuroblastoma Research and Treatments
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Pancreatitis Pathology and Treatment
- Occupational and environmental lung diseases
Blacktown & Mount Druitt Hospital
2017-2025
Westmead Hospital
2016-2025
The University of Sydney
2015-2025
Westmead Institute
2017-2024
Sydney Local Health District
2022-2024
UNSW Sydney
2013-2023
Garvan Institute of Medical Research
2013-2023
Cancer Australia
2016-2023
Pfizer (United States)
2023
Roche (United States)
2023
To assess the frequency and type of oncogenic BRAF mutations in metastatic melanoma correlate status with clinicopathologic features outcome.Consecutive BRAF-tested Australian patients (n = 197) were observed prospectively. A comprehensive range variables correlated mutation status, a survival analysis was conducted.Forty-eight percent had mutation; 70 (74%) V600E, 19 (20%) V600K, six (6%) other genotypes. Other than age at diagnosis distant metastasis (median age, 56 v 63 years for...
We present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE-158 (NCT02628067; phase 2) and KEYNOTE-028 (NCT02054806; 1b) studies. Eligible aged ≥18 years both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, no prior immunotherapy....
BackgroundCurrent staging methods for pancreatic cancer (PC) are inadequate, and biomarkers to aid clinical decision making lacking. Despite the availability of serum marker carbohydrate antigen 19.9 (CA19.9) over two decades, its precise role in management PC is yet be defined, as a consequence, it not widely used.MethodsWe assessed relationship between perioperative CA19.9 levels, survival adjuvant chemotherapeutic responsiveness cohort 260 patients who underwent operative resection...
Fine-tuned manipulation of tumor tension and vasculature enhances response to chemotherapy impairs metastatic spread in pancreatic cancer.
Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices International Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets patients with aberrations their tumor that could be targeted currently available therapies.
<h3>Importance</h3> Biliary tract cancers represent a rare group of malignant conditions with very limited treatment options. Patients advanced disease have poor outcome current therapies. <h3>Objective</h3> To evaluate the efficacy and safety combination immunotherapy nivolumab ipilimumab in patients biliary cancers. <h3>Design, Setting, Participants</h3> The CA209-538 prospective multicenter phase 2 nonrandomized clinical trial included including This subgroup analysis evaluated 39 from...
•First-in-human phase 1 study in patients with advanced solid tumors who received vibostolimab alone or pembrolizumab.•Vibostolimab plus pembrolizumab was well tolerated tumors.•Vibostolimab demonstrated antitumor activity tumors. BackgroundIn this first-in-human (NCT02964013; MK-7684-001), we investigated the safety and efficacy of anti-TIGIT (T cell immunoglobulin ITIM domain) antibody as monotherapy combination pembrolizumab.Patients methodsPart A enrolled tumors, part B non-small-cell...
Abstract Purpose: Combination immunotherapy with anti–CTLA-4 and anti–PD-1 blockade has demonstrated significant clinical activity across several tumor types. Neuroendocrine tumors (NET) are a heterogeneous group of rare limited treatment options. CA209-538 is trial combination ipilimumab nivolumab in cancers, including advanced NETs. Patients Methods: prospective multicenter patients cancers. received at dose 3 mg/kg 1 every three weeks for four doses, followed by two continued up to 96...
Abstract The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance this crosslinking and stabilizing fibrillar collagens its known role tumor desmoplasia. Using small-molecule drug-design approaches, we generated validated PXS-5505, first-in-class highly selective potent pan-lysyl inhibitor. We demonstrate vitro vivo that inhibition decreases chemotherapy-induced pancreatic desmoplasia stiffness, reduces cancer cell invasion metastasis,...
PURPOSE Phase III studies of intravenous amivantamab demonstrated efficacy across epidermal growth factor receptor ( EGFR )–mutated advanced non–small cell lung cancer (NSCLC). A subcutaneous formulation could improve tolerability and reduce administration time while maintaining efficacy. PATIENTS AND METHODS Patients with -mutated NSCLC who progressed after osimertinib platinum-based chemotherapy were randomly assigned 1:1 to receive or amivantamab, both combined lazertinib. Coprimary...
Purpose Individuals with adenocarcinoma of the ampulla Vater demonstrate a broad range outcomes, presumably because these cancers may arise from any one three epithelia that converge at location. This variability poses challenges for clinical decision making and development novel therapeutic strategies. Patients Methods We assessed potential utility histomolecular phenotypes defined using combination histopathology protein expression (CDX2 MUC1) in 208 patients independent cohorts who...
4079 Background: Antitumor activity with pembro, an anti–PD-1 antibody, has been observed in patients (pts) advanced/metastatic biliary tract cancers (BTC), who have limited treatment options. We present follow-up data from pts advanced BTC treated pembro the KN158 (NCT02628067; phase 2) and KN028 (NCT02054806; 1) studies. Methods: Eligible ≥18 y KN158/KN028 cohorts had histologically/cytologically confirmed incurable that progressed after/failed any number of prior standard regimens,...
Pancreatic cancer is one of the most lethal and molecularly diverse malignancies. Repurposing therapeutics that target specific molecular mechanisms in different disease types offers potential for rapid improvements outcome. Although HER2 amplification occurs pancreatic cancer, it inadequately characterized to exploit anti-HER2 therapies.HER2 was detected further analyzed using multiple genomic sequencing approaches. Standardized reference laboratory assays defined a large cohort patients (n...
Objective Extensive molecular heterogeneity of pancreatic ductal adenocarcinoma (PDA), few effective therapies and high mortality make this disease a prime model for advancing development tailored therapies. The p16-cyclin D-cyclin-dependent kinase 4/6-retinoblastoma (RB) protein (CDK4) pathway, regulator cell proliferation, is deregulated in PDA. Our aim was to develop novel personalised treatment strategy PDA based on targeting CDK4. Design Sensitivity potent CDK4/6 inhibitor PD-0332991...
Pancreatic ductal adenocarcinoma (PDAC) can be divided into transcriptomic subtypes with two broad lineages referred to as classical (pancreatic) and squamous. We find that these are driven by distinct metabolic phenotypes. Loss of genes drive endodermal lineage specification, HNF4A GATA6, switch profiles from predominantly squamous, glycogen synthase kinase 3 beta (GSK3β) a key regulator glycolysis. Pharmacological inhibition GSK3β results in selective sensitivity the squamous subtype;...
PURPOSE Lifirafenib is an investigational, reversible inhibitor of B-RAF V600E , wild-type A-RAF, B-RAF, C-RAF, and EGFR. This first-in-human, phase I, dose-escalation/dose-expansion study evaluated the safety, tolerability, efficacy lifirafenib in patients with B-RAF– or K-RAS/N-RAS–mutated solid tumors. METHODS During dose escalation, adult histologically/cytologically confirmed advanced tumors received escalating doses lifirafenib. Primary end points were safety/tolerability during...
Quavonlimab (MK-1308), a novel anti-CTLA-4 antibody, in combination with pembrolizumab was investigated phase I study.Dose-escalation (DE) phase: patients advanced/metastatic solid tumors received an initial flat dose of quavonlimab as monotherapy [25 mg (cohort 1), 75 2), or 200 3)] followed by four treatments the same plus every 3 weeks (Q3W). Dose-confirmation (DC): stage IIIB/IV non-small-cell lung cancer (NSCLC) first-line Q3W (arm A), 25 Q6W B), C), E)] pembrolizumab. Primary...
•Primary endpoint of OS with nivolumab plus chemotherapy versus in nonsquamous metastatic NSCLC was not met.•Descriptive analyses showed improved all-randomized and squamous populations.•PFS DOR favored populations.•No firm associations were found between select somatic mutations, TMB, or LIPI score chemotherapy.•Safety consistent previous reports, no new safety signals identified. BackgroundIn CheckMate 227 Part 1, first-line ipilimumab prolonged overall survival (OS) patients...