Andrew Nixon

Overview:

Andrew Nixon, PhD, MBA (Associate Professor of Medicine) is Director of the Phase I Biomarker Laboratory, which brings together clinical, translational and basic research to pursue the development of novel biomarkers defining mechanisms of sensitivity, resistance, and toxicity to given therapeutic drug classes, particularly anti-angiogenic agents. Additionally, the laboratory has been appointed as a Molecular Reference Laboratory for the Alliance oncology cooperative group, a national clinical trial research group sponsored by the National Cancer Institute. The laboratory has quality control procedures in place to address many of the issues involved in clinical trial research including determination of sample quantity, sample integrity, and sample heterogeneity. We have spent considerable time developing robust assays that utilize limited amounts of specimen while providing high quality data. Multiplex ELISA and gene expression arrays are used to analyze serially collected blood and paraffin samples archived from cancer patient clinical trials. This work has the potential to improve the efficacy and toxicity of current therapies and to guide the development of the next generation of anti-angiogenesis therapies for cancer and other diseases.

Positions:

Professor in Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1997

Wake Forest University

Grants:

Preclinical and Human Correlative Studies of a Novel Bruton Tyronsine Kinase Inhibitor in Pancreatic Cancer

Administered By
Medicine, Medical Oncology
Awarded By
Department of Defense
Role
Co Investigator
Start Date
End Date

Plasma Angiome and Serum Androgens as Predictors of Overall Survival in Metastatic Prostate Cancer

Administered By
Biostatistics & Bioinformatics
Awarded By
Department of Defense
Role
Partnering PI
Start Date
End Date

(PQA5) 'Dose and Mechanisms of Exercise in Breast Cancer Prevention'

Administered By
Radiation Oncology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Anti-VEGF in Tumors & Wounds: Efficacy vs Toxicity

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Regulation Of Cyclic Gmp Phosphodiesterase By Gz

Administered By
Pharmacology & Cancer Biology
Awarded By
National Institutes of Health
Role
PI-Fellow
Start Date
End Date

Publications:

A phase II study of savolitinib (volitinib, AZD6094, HMPL-504) in subjects with MET amplified metastatic colorectal cancer (mCRC) detected by cell-free (cf)DNA

Authors
Jia, J; Niedzwiecki, D; Arrowood, C; Garett-Mead, N; Nagy, R; Lanman, RB; Wright, J; Nixon, AB; Strickler, JH
URI
https://scholars.duke.edu/individual/pub1444228
Source
wos-lite
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
38
Published Date

Prognostic and Predictive Biomarkers in Metastatic Colorectal Cancer Patients Receiving Regorafenib.

Regorafenib is a tyrosine kinase inhibitor approved by the Food and Drug Administration (FDA) for the treatment of chemotherapy-refractory metastatic colorectal cancer (mCRC) patients. Regorafenib inhibits signaling through multiple receptors associated with angiogenesis, metastasis, and tumor immunity. Here we report biomarker results from LCCC1029, a randomized, placebo controlled, phase II trial of chemotherapy ± regorafenib in second-line mCRC patients. A panel of 20 soluble protein biomarkers (termed the Angiome) was assessed in the plasma of 149 patients from the LCCC1029 trial both at baseline and along the treatment continuum. Baseline protein levels were analyzed for prognostic and predictive value for progression-free survival (PFS) and overall survival (OS). Changes in protein levels during treatment were analyzed for potential pharmacodynamic effects. Six markers (HGF, IL-6, PlGF, VEGF-R1, OPN, and IL-6R) were found to be prognostic for PFS. Nine markers (IL-6, TIMP-1, PlGF, VCAM-1, ICAM-1, OPN, TSP-2, HGF, and VEGF-R1) were prognostic for OS. Higher baseline levels of OPN (Pintx=0.0167), VCAM-1 (Pintx=0.0216), and PDGF-AA (Pintx=0.0435) appeared to predict for PFS benefit from regorafenib compared to placebo. VCAM-1 was also potentially predictive of OS benefit from regorafenib compared to placebo (Pintx=0.0124). On-treatment changes of six markers reflected potential on-target effect of regorafenib. Consistent results were observed in an Italian cohort where 105 late-stage mCRC patients received regorafenib monotherapy. The key findings of this study suggest that VCAM-1 may be a predictive biomarker for regorafenib benefit while multiple protein markers may be prognostic of outcome in mCRC patients.
Authors
Liu, Y; Lyu, J; Bell Burdett, K; Sibley, AB; Hatch, AJ; Starr, MD; Brady, JC; Hammond, K; Marmorino, F; Rossini, D; Goldberg, RM; Falcone, A; Cremolini, C; Owzar, K; Ivanova, A; Moore, DT; Lee, MS; Sanoff, HK; Innocenti, F; Nixon, AB
MLA Citation
Liu, Yingmiao, et al. “Prognostic and Predictive Biomarkers in Metastatic Colorectal Cancer Patients Receiving Regorafenib.Mol Cancer Ther, Aug. 2020. Pubmed, doi:10.1158/1535-7163.MCT-20-0249.
URI
https://scholars.duke.edu/individual/pub1453716
PMID
32747417
Source
pubmed
Published In
Mol Cancer Ther
Published Date
DOI
10.1158/1535-7163.MCT-20-0249

Combination of PARP Inhibitor Olaparib, and PD-L1 Inhibitor Durvalumab, in Recurrent Ovarian Cancer: a Proof-of-Concept Phase II Study.

PURPOSE: Preclinical studies suggest PARP inhibition (PARPi) induces immunostimulatory micromilieu in ovarian cancer thus complementing activity of immune checkpoint blockade. We conducted a phase II trial of PARPi olaparib and anti-PD-L1 durvalumab and collected paired fresh core biopsies and blood samples to test this hypothesis. PATIENTS AND METHODS: In a single-center, proof-of-concept phase II study, we enrolled women aged ≥18 with recurrent ovarian cancer. All patients were immune checkpoint inhibitor-naïve and had measurable disease per RECISTv1.1, ECOG performance status 0-2, and adequate organ and marrow function. Patients received olaparib 300 mg twice daily and durvalumab 1,500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Primary endpoint was overall response rate (ORR). Secondary objectives were safety and progression-free survival (PFS). Translational objectives included biomarker evaluation for relationships with clinical response and immunomodulatory effects by treatment. RESULTS: Thirty-five patients with ovarian cancer [median, four prior therapies (IQR, 2-5.5), predominantly platinum-resistant (86%), BRCA wild-type (77%)] received at least one full cycle of treatment. ORR was 14% [5/35; 95% confidence interval (CI), 4.8%-30.3%]. Disease control rate (PR+SD) was 71% (25/35; 95% CI, 53.7%-85.4%). Treatment enhanced IFNγ and CXCL9/CXCL10 expression, systemic IFNγ/TNFα production, and tumor-infiltrating lymphocytes, indicating an immunostimulatory environment. Increased IFNγ production was associated with improved PFS [HR, 0.37 (95% CI, 0.16-0.87), P = 0.023], while elevated VEGFR3 levels were associated with worse PFS (HR, 3.22 (95% CI, 1.23-8.40), P = 0.017]. CONCLUSIONS: The PARPi and anti-PD-L1 combination showed modest clinical activity in recurrent ovarian cancer. Our correlative study results suggest immunomodulatory effects by olaparib/durvalumab in patients and indicate that VEGF/VEGFR pathway blockade would be necessary for improved efficacy of the combination.
Authors
Lampert, EJ; Zimmer, A; Padget, M; Cimino-Mathews, A; Nair, JR; Liu, Y; Swisher, EM; Hodge, JW; Nixon, AB; Nichols, E; Bagheri, MH; Levy, E; Radke, MR; Lipkowitz, S; Annunziata, CM; Taube, JM; Steinberg, SM; Lee, J-M
MLA Citation
Lampert, Erika J., et al. “Combination of PARP Inhibitor Olaparib, and PD-L1 Inhibitor Durvalumab, in Recurrent Ovarian Cancer: a Proof-of-Concept Phase II Study.Clin Cancer Res, May 2020. Pubmed, doi:10.1158/1078-0432.CCR-20-0056.
URI
https://scholars.duke.edu/individual/pub1441168
PMID
32398324
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Published Date
DOI
10.1158/1078-0432.CCR-20-0056

Bayesian machine learning on CALGB/SWOG 80405 (Alliance) and PEAK data identify a heterogeneous landscape of clinical predictors of overall survival (OS) in different populations of metastatic colorectal cancer (mCRC).

Authors
Das, R; Ou, F; Washburn, C; Innocenti, F; Nixon, A; Lenz, H; Blanke, C; Niedzwiecki, D; Khalil, I; Harms, B; Venook, A
URI
https://scholars.duke.edu/individual/pub1402991
PMID
32084987
Source
pubmed
Published In
Ann Oncol
Volume
30 Suppl 4
Published Date
Start Page
iv116
DOI
10.1093/annonc/mdz156.019

Developing elite Neurospora crassa strains for cellulosic ethanol production using fungal breeding.

The demand for renewable and sustainable energy has generated considerable interest in the conversion of cellulosic biomass into liquid fuels such as ethanol using a filamentous fungus. While attempts have been made to study cellulose metabolism through the use of knock-out mutants, there have been no systematic effort to characterize natural variation for cellulose metabolism in ecotypes adapted to different habitats. Here, we characterized natural variation in saccharification of cellulose and fermentation in 73 ecotypes and 89 laboratory strains of the model fungus Neurospora crassa. We observed significant variation in both traits among natural and laboratory generated populations, with some elite strains performing better than the reference strain. In the F1 population N345, 15% of the population outperformed both parents with the top performing strain having 10% improvement in ethanol production. These results suggest that natural alleles can be exploited through fungal breeding for developing elite industrial strains for bioethanol production.
Authors
Waters, JC; Nixon, A; Dwyer, M; Biffinger, JC; Lee, K
MLA Citation
Waters, Joshua C., et al. “Developing elite Neurospora crassa strains for cellulosic ethanol production using fungal breeding.J Ind Microbiol Biotechnol, vol. 44, no. 8, Aug. 2017, pp. 1137–44. Pubmed, doi:10.1007/s10295-017-1941-0.
URI
https://scholars.duke.edu/individual/pub1438795
PMID
28429154
Source
pubmed
Published In
J Ind Microbiol Biotechnol
Volume
44
Published Date
Start Page
1137
End Page
1144
DOI
10.1007/s10295-017-1941-0