Tian Zhang

Positions:

Associate 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:

Defining the Relevant Immune Checkpoints Expressed on Metastatic Prostate Cancer Circulating Tumor Cells

Administered By
Duke Cancer Institute
Awarded By
Janssen Research & Development, LLC
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
Awarded By
Merck
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
Awarded By
Janssen Pharmaceutica, Inc.
Role
Principal Investigator
Start Date
End Date

MM-310-01-01-01: A Phase 1 Study Evaluating the Safety, Pharmacology and Preliminary Activity of MM-310 in Patients with Solid Tumors

Administered By
Duke Cancer Institute
Awarded By
Merrimack Pharmaceuticals
Role
Principal Investigator
Start Date
End Date

Publications:

A prospective trial of abiraterone acetate plus prednisone in Black and White men with metastatic castrate-resistant prostate cancer.

BACKGROUND: Retrospective analyses of randomized trials suggest that Black men with metastatic castration-resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. METHODS: This race-stratified, multicenter study estimated radiographic progression-free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate-specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome-wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self-identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. RESULTS: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. CONCLUSIONS: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side-effect rates than White men. This exploratory genome-wide analysis of TTP identified a possible candidate marker of ancestry-dependent treatment outcomes.
Authors
George, DJ; Halabi, S; Heath, EI; Sartor, AO; Sonpavde, GP; Das, D; Bitting, RL; Berry, W; Healy, P; Anand, M; Winters, C; Riggan, C; Kephart, J; Wilder, R; Shobe, K; Rasmussen, J; Milowsky, MI; Fleming, MT; Bearden, J; Goodman, M; Zhang, T; Harrison, MR; McNamara, M; Zhang, D; LaCroix, BL; Kittles, RA; Patierno, BM; Sibley, AB; Patierno, SR; Owzar, K; Hyslop, T; Freedman, JA; Armstrong, AJ
MLA Citation
URI
https://scholars.duke.edu/individual/pub1481831
PMID
33951180
Source
pubmed
Published In
Cancer
Published Date
DOI
10.1002/cncr.33589

The Immunotherapy Landscape in Renal Cell Carcinoma.

The past 30 years have borne witness to a gradual evolution in the treatment landscape of advanced renal cell carcinoma (aRCC). Early immunotherapy approaches such as interferon-α and high-dose interleukin-2 (IL-2) therapy in this immunogenic tumor provided durable responses in only a minority of patients and came with toxic side effects. A growing understanding of the tumor biology elucidated pathways of tumorigenesis, which in turn revealed novel targets amenable to targeted therapies. Inhibition of angiogenesis and cell signaling emerged as cornerstones of treatment with the approval of bevacizumab and several pan-kinase and tyrosine kinase inhibitors. Though effective, their use has been limited by low rates of durable response, resistance, and side effects. The immunotherapy revolution of the past decade has led to immunotherapy-based combination regimens such as ipilimumab plus nivolumab, pembrolizumab plus axitinib, and avelumab plus axitinib, displacing single agent anti-angiogenic therapy in the first-line setting by demonstrating durable responses and improved survival over sunitinib. These immunotherapy-based combinations define first-line standard of care for aRCC today. The pipeline of second-line agents for consideration in patients who have disease progression despite immunotherapy regimens is robust but still in early stages of development.
Authors
Brown, LC; Desai, K; Zhang, T; Ornstein, MC
MLA Citation
Brown, Landon C., et al. “The Immunotherapy Landscape in Renal Cell Carcinoma.Biodrugs, vol. 34, no. 6, Dec. 2020, pp. 733–48. Pubmed, doi:10.1007/s40259-020-00449-4.
URI
https://scholars.duke.edu/individual/pub1462315
PMID
33048299
Source
pubmed
Published In
Biodrugs
Volume
34
Published Date
Start Page
733
End Page
748
DOI
10.1007/s40259-020-00449-4

PDIGREE: An adaptive phase III trial of PD-inhibitor nivolumab and ipilimumab (IPI-NIVO) with VEGF TKI cabozantinib (CABO) in metastatic untreated renal cell cancer (Alliance A031704).

Authors
Zhang, T; Ballman, KV; Choudhury, AD; Chen, RC; Watt, C; Wen, Y; Shergill, A; Zemla, TJ; Emamekhoo, H; Vaishampayan, UN; Morris, MJ; George, DJ; Choueiri, TK
URI
https://scholars.duke.edu/individual/pub1475818
Source
wos-lite
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
38
Published Date

387 A Phase II, multicenter study of the safety and efficacy of LAG525 in combination with spartalizumab in patients with advanced malignancies

<jats:sec><jats:title>Background</jats:title><jats:p>Expression of LAG-3, an inhibitory immunoreceptor, has been linked to reduced T-cell proliferation and cytokine production. LAG525 is a humanized IgG4 anti-LAG-3 antibody which inhibits LAG-3 binding to MHC class II. Spartalizumab is a humanized IgG4 anti-PD-1 mAb which inhibits PD-1 binding with its ligands PD-L1 and PD-L2. Preclinical data have shown promising antitumor activity when blocking LAG-3 and PD-1.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>The Phase II part of the first-in-human study (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT02460224">NCT02460224</jats:ext-link>) explored LAG525 + spartalizumab in patients with advanced/metastatic non-small cell lung cancer (NSCLC), cutaneous and non-cutaneous melanoma, renal cell carcinoma (RCC), mesothelioma, or triple-negative breast cancer (TNBC). The dose/schedule of LAG525 and spartalizumab was 400 mg IV Q3W and 300 mg IV Q3W, respectively. Half of patients with TNBC naïve to anti-PD-1/PD-L1 received LAG525 at 600 mg IV Q4W and spartalizumab at 400 mg IV Q4W. The primary endpoint was overall response rate (ORR) using RECIST v1.1.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>As of June 1, 2020, 235 patients were enrolled in the Phase II part of the study, including patients with NSCLC (n=42), melanoma (n=42), RCC (n=38), mesothelioma (n=57), or TNBC (n=56). In total, 142 patients were naïve to, and 93 patients were pretreated with, PD-1/PD-L1 inhibitors. Overall, 232 patients (99%) discontinued treatment, 76% due to progressive disease.ORR and disease control rate by indication and prior anti-PD-1/PD-L1 treatment are summarized below (table 1). Best overall response was 3 (1.3%) CR, 23 (9.8%) PR, 84 (35.7%) SD, 95 (40.4%) PD, and 30 (12.8%) unknown. For patients naïve to anti-PD-1/PD-L1, median progression free survival (mPFS) in months (90% CI) was 3.9 (1.7–5.6) for NSCLC, 2.2 (1.6–5.6) for melanoma, 4.4 (2.1–11.1) for RCC, 5.5 (3.5–6.4) for mesothelioma, and 1.9 (1.6–2.6) for TNBC. For patients pretreated with anti-PD-1/PD-L1, mPFS in months (90% CI) was 3.5 (1.9–4.9) for NSCLC, 1.9 (1.8–3.7) for melanoma, 3.0 (1.6–3.9) for RCC, 3.4 (1.8–3.8) for mesothelioma, and 1.7 (1.3–3.4) for TNBC. Adverse events of any grade, regardless of cause, were reported in 233 (99%) patients; the most common (occurring in &gt;20%) were nausea (25%), fatigue (23%), and dyspnea (21%).</jats:p><jats:table-wrap id="T1" position="float" orientation="portrait"><jats:label>Abstract 387 Table 1</jats:label><jats:caption><jats:p>Overall response rate (ORR: CR + PR) and disease control rate (DCR: CR + PR + SD) per RECIST v1.1 by indication and prior anti-PD-1/PD-L1 treatment</jats:p></jats:caption><jats:graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="ABS_387_T001" position="float" orientation="portrait" /></jats:table-wrap></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>LAG525 + spartalizumab exhibited antitumor activity across different indications, including patients with melanoma, RCC, and mesothelioma who had been pretreated with PD-1/-L1 inhibitors, suggesting that this combination may salvage prior PD-1/-L1 resistance. The combination was well tolerated, and no new safety signals were observed. Biomarker analysis is ongoing.</jats:p></jats:sec><jats:sec><jats:title>Trial Registration</jats:title><jats:p>NCT02460224</jats:p></jats:sec><jats:sec><jats:title>Ethics Approval</jats:title><jats:p>This study was approved by an independent ethics committee or institutional review board at each site.</jats:p></jats:sec>
Authors
Lin, C-C; Garralda, E; Schöffski, P; Hong, D; Siu, L; Martin, M; Maur, M; Hui, R; Soo, R; Chiu, J; Zhang, T; Ma, B; Kyi, C; Tan, D; Cassier, P; Sarantopoulos, J; Weickhardt, A; Carvajal, R; Spratlin, J; Esaki, T; Rolland, F; Akerley, W; Deschler-Baier, B; Sabatos-Peyton, C; Chowdhury, NR; Gusenleitner, D; Kwak, E; Askoxylakis, V; Braud, FD
MLA Citation
Lin, Chia-Chi, et al. “387 A Phase II, multicenter study of the safety and efficacy of LAG525 in combination with spartalizumab in patients with advanced malignancies.” Journal for Immunotherapy of Cancer, vol. 8, no. Suppl 3, BMJ, 2020, pp. A412–A412. Crossref, doi:10.1136/jitc-2020-sitc2020.0387.
URI
https://scholars.duke.edu/individual/pub1475821
Source
crossref
Published In
Journal for Immunotherapy of Cancer
Volume
8
Published Date
Start Page
A412
End Page
A412
DOI
10.1136/jitc-2020-sitc2020.0387

ApricityRx companion digital therapeutic for evidence-based mitigation and phenotype-linked molecular characterization of irAEs in patients receiving immune checkpoint therapy (ICT).

Authors
Campbell, MT; Zhang, T; Chin, L; Warner, AB; Mathew, M
URI
https://scholars.duke.edu/individual/pub1475819
Source
wos-lite
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
38
Published Date