Tian Zhang

Positions:

Assistant Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2009

Harvard Medical School

M.H.S. 2019

Duke University School of Medicine

Internal Medicine Residency, Medicine

Duke University School of Medicine

Fellowship in Hematology-Oncology, Medicine

Duke University School of Medicine

Grants:

Duke-UNC-Wash U Partnership for Early Phase Clinical Trials in Cancer

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Significant Contributor
Start Date
End Date

CTC-Immune Checkpoints

Administered By
Duke Cancer Institute
Role
Co-Principal Investigator
Start Date
End Date

Conditional lethality of copper and disulfiram as a therapeutic modality for prostate cancer

Administered By
Medicine, Medical Oncology
Awarded By
V Foundation for Cancer Research
Role
Principal Investigator
Start Date
End Date

A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Pembrolizumab (MK-3475) as Monotherapy in the Adjuvant Treatment of Renal Cell Carcinoma Post Nephrectomy (KEYNOTE-564)

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

A Salvage Trial of AR Inhibition with ADT and Apalutamide with Docetaxel followed by Radiation Therapy in Men with PSA Recurrent Prostate Cancer after Radical Prostatectomy (¿STARTAR¿)

Administered By
Duke Cancer Institute
Role
Principal Investigator
Start Date
End Date

Publications:

Characterization of tumor mutation burden, PD-L1 and DNA repair genes to assess relationship to immune checkpoint inhibitors response in metastatic renal cell carcinoma.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have expanded treatment options for metastatic renal cell carcinoma (mRCC); however, there are limited predictive biomarkers for response to ICIs in this indication, with programmed death-ligand 1 (PD-L1) status demonstrating little predictive utility in mRCC. While predictive of ICI response in other tumor types, the utility of tumor mutation burden (TMB) in mRCC is unclear. Here, we assess TMB, loss of antigen presentation genes and PD-L1 status correlated with outcomes to ICI treatment in mRCC. METHODS: Tumor samples from 34 patients with mRCC treated with ICI therapy at Duke Cancer Institute were retrospectively evaluated using Personal Genome Diagnostics elio tissue complete (RUO version), a tumor genomic profiling assay for somatic variants, TMB, microsatellite status and genomic status of antigen presentation genes. Tumor samples were also analyzed with the Dako 28-8 PD-L1 immunohistochemistry assay. Deidentified clinical information was extracted from the medical record, and tumor response was evaluated based on the Response Evaluation Criteria In Solid Tumors (RECIST) V.1.1 criteria. RESULTS: Patients were stratified by overall response following ICI therapy and designated as progressive disease (PD; n=18) or disease control groups (DC; n=16). TMB scores ranged from 0.36 to 12.24 mutations/Mb (mean 2.83 mutations/Mb) with no significant difference between the PD and DC groups (3.01 vs 2.63 mutations/Mb, respectively; p=0.7682). Interestingly, 33% of PD patients displayed loss of heterozygosity of major histocompatibility complex class I genes (LOH-MHC) vs 6% of DC patients. Nine of 34 samples were PD-L1-positive (4 in the PD group; 5 in the DC group), suggesting no correlation between PD-L1 expression and response to ICI therapy. Notably, the DC group displayed an enrichment of mutations in DNA repair genes (p=0.04), with 68.8% exhibiting at least one mutated homologous recombination repair (HRR)-related gene compared with only 38.9% of the PD group (p=0.03). CONCLUSIONS: Overall, neither TMB nor PD-L1 correlated with ICI response and TMB was not significantly associated with PD-L1 expression. The higher incidence of LOH-MHC in PD group suggests that loss of antigen presentation may restrict response to ICIs. Separately, enrichment of HRR gene mutations in the DC group suggests potential utility in predicting ICI response and a potential therapeutic target, warranting future studies.
Authors
Labriola, MK; Zhu, J; Gupta, R; McCall, S; Jackson, J; Kong, EF; White, JR; Cerqueira, G; Gerding, K; Simmons, JK; George, D; Zhang, T
MLA Citation
Labriola, Matthew Kyle, et al. “Characterization of tumor mutation burden, PD-L1 and DNA repair genes to assess relationship to immune checkpoint inhibitors response in metastatic renal cell carcinoma.J Immunother Cancer, vol. 8, no. 1, Mar. 2020. Pubmed, doi:10.1136/jitc-2019-000319.
URI
https://scholars.duke.edu/individual/pub1435838
PMID
32221016
Source
pubmed
Published In
Journal for Immunotherapy of Cancer
Volume
8
Published Date
DOI
10.1136/jitc-2019-000319

Abstract CT162: Pembrolizumab monotherapy for the adjuvant treatment of renal cell carcinoma post-nephrectomy: Randomized, double-blind, Phase III KEYNOTE-564 study

Authors
Choueiri, TK; Quinn, DI; Zhang, T; Gurney, H; Doshi, GK; Cobb, PW; Parnis, F; Lee, J-L; Park, SH; Semenov, A; Thiery-Vuillemin, A; Sawrycki, P; Tomczak, P; Alekseev, B; Izmailov, A; Chang, WY-H; Wan, SM; Poehlein, CH; Willemann-Rogerio, J; Powles, T
MLA Citation
Choueiri, Toni K., et al. “Abstract CT162: Pembrolizumab monotherapy for the adjuvant treatment of renal cell carcinoma post-nephrectomy: Randomized, double-blind, Phase III KEYNOTE-564 study.” Clinical Trials, American Association for Cancer Research, 2019. Crossref, doi:10.1158/1538-7445.am2019-ct162.
URI
https://scholars.duke.edu/individual/pub1416793
Source
crossref
Published In
Clinical Trials
Published Date
DOI
10.1158/1538-7445.am2019-ct162

Immune profiling in a randomized phase II trial of acalabrutinib and pembrolizumab (PA) versus pembrolizumab (P) for patients with metastatic urothelial cancer (mUC).

Authors
Zhang, T; Staats, JS; Chan, C; Harrison, MR; O'Donnell, PH; Batich, KA; Chen, T; Krejsa, C; Izumi, R; George, DJ; Weinhold, KJ
MLA Citation
Zhang, Tian, et al. “Immune profiling in a randomized phase II trial of acalabrutinib and pembrolizumab (PA) versus pembrolizumab (P) for patients with metastatic urothelial cancer (mUC).Journal of Clinical Oncology, vol. 36, no. 15_suppl, American Society of Clinical Oncology (ASCO), 2018, pp. 4533–4533. Crossref, doi:10.1200/jco.2018.36.15_suppl.4533.
URI
https://scholars.duke.edu/individual/pub1437026
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
36
Published Date
Start Page
4533
End Page
4533
DOI
10.1200/jco.2018.36.15_suppl.4533

Disulfiram (DSF) pharmacokinetics (PK) and copper PET imaging in a phase Ib study of intravenous (IV) copper loading with oral DSF for patients with metastatic castration-resistant prostate cancer (mCRPC)

Authors
Zhang, T; Kephart, J; Bronson, E; Anand, M; Daly, C; Spasojevic, I; Berg, H; James, OG; Healy, P; Halabi, S; Harrison, MR; Armstrong, AJ; George, DJ
URI
https://scholars.duke.edu/individual/pub1441131
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
38
Published Date

Longitudinal multiplex cytokine analysis for patients (pts) with metastatic renalcell carcinoma (mRCC) treated with ipilimumab/nivolumab (I plus N).

Authors
Zhang, T; Wu, Y; Agarwal, A; Starr, MD; Reyes-Martinez, M; Anand, M; Runyambo, D; Harrison, MR; Armstrong, AJ; George, DJ; Nixon, AB
MLA Citation
Zhang, Tian, et al. “Longitudinal multiplex cytokine analysis for patients (pts) with metastatic renalcell carcinoma (mRCC) treated with ipilimumab/nivolumab (I plus N).Journal of Clinical Oncology, vol. 38, no. 6, AMER SOC CLINICAL ONCOLOGY, 2020.
URI
https://scholars.duke.edu/individual/pub1441188
Source
wos
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
38
Published Date