James Abbruzzese
Overview:
My research interests include the clinical study and treatment of pancreatic cancer.
Positions:
D. C. I. Distinguished Professor of Medical Oncology
Medicine, Medical Oncology
School of Medicine
Professor of Medicine
Medicine, Medical Oncology
School of Medicine
Member of the Duke Cancer Institute
Duke Cancer Institute
School of Medicine
Education:
M.D. 1978
The University of Chicago
Intern, Internal Medicine
Johns Hopkins University School of Medicine
Resident, Internal Medicine
Johns Hopkins University School of Medicine
Grants:
Topic Refinement, Task order 9 Topic Briefs
Administered By
Duke Clinical Research Institute
Awarded By
Patient Centered Outcomes Research Institute
Role
Co Investigator
Start Date
End Date
Pfizer - C4201002 - PF-07265807
Administered By
Duke Cancer Institute
Awarded By
Pfizer, Inc.
Role
Principal Investigator
Start Date
End Date
A PHASE 1 DOSE ESCALATION AND EXPANSION STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07257876 IN PATIENTS WITH ADVANCED OR METASTATIC TUMORS
Administered By
Duke Cancer Institute
Awarded By
Pfizer, Inc.
Role
Principal Investigator
Start Date
End Date
A phase 1/1b/2 study evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AMG 193 alone and in combination with docetaxel in subjects with advanced MTAP-null solid tumors
Administered By
Duke Cancer Institute
Awarded By
Amgen, Inc.
Role
Principal Investigator
Start Date
End Date
Cancer Therapy Evaluation Program Administrative Agreement
Administered By
Duke Cancer Institute
Awarded By
Leidos Biomedical Research, Inc.
Role
Principal Investigator
Start Date
End Date
Publications:
Design of a Phase 1 Study of AMG 193, an MTA-Cooperative PRMT5 Inhibitor, in Patients with Advanced MTAP-Null Solid Tumors
Authors
Calero, MV; Patnaik, A; Maki, R; O'Neil, B; Abbruzzese, J; Dagogo-Jack, I; Devarakonda, S; Wahlroos, S; Lin, CC; Fujiwara, Y; Terbuch, A; Postel-Vinay, S; Goebeler, ME; Addeo, A; Prenen, H; Arkenau, T; Sacher, A; Liu, C; Kormany, W; Ahnert, J
MLA Citation
Calero, M. Villalona, et al. “Design of a Phase 1 Study of AMG 193, an MTA-Cooperative PRMT5 Inhibitor, in Patients with Advanced MTAP-Null Solid Tumors.” Journal of Thoracic Oncology, vol. 17, no. 9, 2022, pp. S457–S457.
URI
https://scholars.duke.edu/individual/pub1556022
Source
wos-lite
Published In
Journal of Thoracic Oncology
Volume
17
Published Date
Start Page
S457
End Page
S457
Comprehensive genomic and transcriptomic characterization of small bowel adenocarcinoma.
Authors
Pandya, K; Xiu, J; Farrell, A; Overman, MJ; Seeber, A; Abraham, J; Shields, AF; Lou, E; Marshall, J; Abbruzzese, JL; Heinz-Josef,; Korn, LWM; Gulhati, P
MLA Citation
Pandya, Karan, et al. “Comprehensive genomic and transcriptomic characterization of small bowel adenocarcinoma.” Journal of Clinical Oncology, vol. 40, no. 16, 2022.
URI
https://scholars.duke.edu/individual/pub1556023
Source
wos-lite
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
40
Published Date
Design and rationale of a phase 1 dose-escalation study of AMG 193, a methylthioadenosine (MTA)-cooperative PRMT5 inhibitor, in patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors
Authors
Villalona-Calero, MA; Patnaik, A; Maki, RG; O'Neil, B; Abbruzzese, JL; Dagogo-Jack, I; Devarakonda, S; Wahlroos, S; Lin, C-C; Fujiwara, Y; Terbuch, A; Postel-Vinay, S; Goebeler, M-E; Addeo, A; Prenen, H; Arkenau, T; Sacher, AG; Liu, C; Kormany, W; Ahnert, JR
MLA Citation
Villalona-Calero, Miguel Angel, et al. “Design and rationale of a phase 1 dose-escalation study of AMG 193, a methylthioadenosine (MTA)-cooperative PRMT5 inhibitor, in patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors.” Journal of Clinical Oncology, vol. 40, no. 16, 2022.
URI
https://scholars.duke.edu/individual/pub1556024
Source
wos-lite
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
40
Published Date
Trials in progress: A phase 1, open-label, dose-escalation, pharmacokinetic, safety and tolerability study of the selective TAM kinase inhibitor PF-07265807 in patients with advanced or metastatic solid tumors.
<jats:p> TPS2671 </jats:p><jats:p> Background: MERTK is a receptor tyrosine kinase from the tumor-associated macrophage kinase (TAMK) family that regulates key aspects of immune homeostasis and responses to infection. MERTK inhibition may lower the threshold for immune activation thereby promoting anti-tumor activity. Agents with some degree of MERTK inhibitory activity have been investigated in the clinic, but are limited by poor potency in patients (pts) and significant off-targets effects. PF-07265807 (ARRY-067) is a selective small-molecule inhibitor of the TAMKs MERTK and AXL. In preclinical models, PF-07265807 monotherapy shows antitumor activity that results in long-term cures and resistance to tumor re-challenge when combined with anti-programmed cell death protein 1/programmed death-ligand 1 (anti-PD-1/PD-L1) antibodies. This first-in-human study will evaluate the safety, tolerability, pharmacokinetics (PK) and preliminary anti-tumor activity of PF-07265807 in pts with selected advanced or metastatic solid tumors. This study will also explore the potential utility of PF-07265807 in combination with anti-PD-1/PD-L1 antibodies. Methods: This is a phase 1, open-label, multi-center, dose-escalation study (NCT04458259) to evaluate the safety, PK and tolerability of PF-07265807. Eligible participants will be adult pts with selected advanced or metastatic solid tumors who are intolerant or resistant to standard therapy. Other key eligibility criteria: measurable disease by RECIST 1.1 or non-measurable disease; Eastern Cooperative Oncology Group performance status 0–2; adequate bone marrow, renal and liver function; and resolved acute effects of any prior therapy. Successive cohorts of pts will receive escalating doses of PF-07265807 starting from 25 mg QD. Each cycle will be 21 days in duration (14 days on/7 days off). Study drug treatment will continue until disease progression or unacceptable toxicity, whichever occurs first. For dose escalation, a Bayesian logistic regression model will be used to model the relationship of dose-limiting toxicities (DLTs) to PF-07265807 dose. This model, along with escalation with overdose control, will guide the dose escalation of PF-07265807 after the completion of the DLT observation period (first two cycles of treatment, i.e. 42 days) of each cohort, until determination of the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D). After the MTD/RP2D is identified, the safety and efficacy of combined PF-07265807 and anti-PD1/PD-L1 treatment will be explored. Primary endpoints: incidence of DLTs, treatment-emergent adverse events and laboratory abnormalities. Secondary endpoints: PK parameters of PF-07265807, objective response rate and duration of response. The study began enrolling pts in September 2020 and is still recruiting. Clinical trial information: NCT04458259. </jats:p>
Authors
Subbiah, V; Awad, MM; Daud, A; Gutierrez, M; McDermott, JD; Ou, S-HI; Hirohashi, T; Ingram, K; Oliver, C; Smith, D; Wollenberg, L; Abbruzzese, JL
MLA Citation
Subbiah, Vivek, et al. “Trials in progress: A phase 1, open-label, dose-escalation, pharmacokinetic, safety and tolerability study of the selective TAM kinase inhibitor PF-07265807 in patients with advanced or metastatic solid tumors.” Journal of Clinical Oncology, vol. 39, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. TPS2671–TPS2671. Crossref, doi:10.1200/jco.2021.39.15_suppl.tps2671.
URI
https://scholars.duke.edu/individual/pub1502426
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
TPS2671
End Page
TPS2671
DOI
10.1200/jco.2021.39.15_suppl.tps2671
Carcinoma of Unknown Primary
Carcinoma of unknown primary (CUP) is a diverse group of heterogeneous cancers presenting without a primary site and accounts for about 2% to 4% of all cancers. The past two decades have seen significant change in our approach to CUP patients. Therapy strategies have moved away from the empiric combination cytotoxic therapies and the “one treatment fits all” approach. The primary focus has been on improved methods to identify the putative primary tumor and to direct therapy at that tumor type. Albeit not uniform, there is consensus that the evaluation needs to be focused, with imaging and invasive tests based on symptomatology and pathologic evaluation. Although it has limitations including variable tissue antigenicity and interpretation, immunohistochemistry remains a powerful tool in the judicious pathologic assessment of metastatic tumor tissue. Over the last several years, cancer classifying tissue of origin profiling libraries has generated enormous data, analyses of which have led to additional insights. Using next generation sequencing, there is a push toward personalizing cancer care through the use of genomic tools to identify driver and actionable mutations in individual tumors. For this approach to be successful in CUP, it will require continued understanding of unique molecular insights for select CUP subsets, as well as leveraging novel drugs that are effective against specific mutations in known cancers.
Authors
Varadhachary, G; Abbruzzese, JL
MLA Citation
Varadhachary, G., and J. L. Abbruzzese. “Carcinoma of Unknown Primary.” Abeloff’s Clinical Oncology, 2019, pp. 1694–702. Scopus, doi:10.1016/B978-0-323-47674-4.00091-8.
URI
https://scholars.duke.edu/individual/pub1509546
Source
scopus
Published Date
Start Page
1694
End Page
1702
DOI
10.1016/B978-0-323-47674-4.00091-8
Research Areas:
Adolescent
Adult
Age Distribution
Albumins
Animals
Blood Transfusion
Cell Differentiation
Cell Growth Processes
Cell Lineage
Cell Movement
Cell Transformation, Neoplastic
Chemotherapy, Adjuvant
Chi-Square Distribution
Child
Cisplatin
Clinical Competence
Combined Modality Therapy
Cytokines
DNA Repair
Diabetes Complications
Diabetes Mellitus, Type 2
Diagnosis, Differential
Disease Models, Animal
Disease-Free Survival
Drug Delivery Systems
Drug Therapy, Combination
Dyspnea
Epithelial Cells
False Positive Reactions
Fibrosis
Genetic Variation
Genotype
HEK293 Cells
HT29 Cells
Health Status
Homozygote
Hypothyroidism
Immunohistochemistry
Inflammation
Intercellular Signaling Peptides and Proteins
Islets of Langerhans
Isotope Labeling
Liver
Liver Neoplasms
Liver Neoplasms, Experimental
Lymph Nodes
Membrane Proteins
Mesoderm
Models, Biological
Mutation
Neoadjuvant Therapy
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Proteins
Neoplasm Recurrence, Local
Neoplasm Staging
Neoplasms
Nervous System
Odds Ratio
Organoplatinum Compounds
Oxidative Stress
Pain
Pancreas
Pancreatectomy
Pancreatic Ducts
Pancreatic Neoplasms
Pancreaticoduodenectomy
Patient Care Team
Phenotype
Physicians
Polymorphism, Genetic
Probability
Prognosis
Proteolysis
Pyrimidines
Quinazolines
Radiation Tolerance
Radiotherapy, Adjuvant
Reactive Oxygen Species
Reference Values
Reproducibility of Results
Risk
Sensitivity and Specificity
Sepsis
Sex Distribution
Signal Transduction
Thiazoles
Time Factors
Treatment Outcome
Tumor Cells, Cultured
Tumor Markers, Biological
Water
Xenograft Model Antitumor Assays

D. C. I. Distinguished Professor of Medical Oncology
Contact:
440 Mudd Building, Box 3406, Durham, NC 27710
440 Mudd Building, Box 3406, Durham, NC 27710