Andrew Armstrong

Overview:

1. Predictors of sensitivity and clinical efficacy of therapies in advanced prostate cancer
2. Novel designs of clinical trials and pharmacodynamic/translational studies in prostate, kidney, bladder cancer
3. Pre-operative models for drug development of novel agents in human testing in prostate cancer
4. Novel therapies and drug development for prostate, renal, bladder, and testicular cancer
5. Design of rational combination therapies in men with metastatic hormone-refractory prostate cancer
6. PI3 kinase/mTOR inhibition in prostate cancer: mechanisms of sensitivity and resistance
7. Developing prognostic models for progression and survival in metastatic prostate cancer
8. Examining surrogate markers of mortality in metastatic prostate cancer
9. Clear cell and non-clear cell renal cell carcinoma: natural history, sensitivity to novel agents including mTOR and VEGF inhibition

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor in Surgery

Surgery, Urology
School of Medicine

Professor in Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S.E. 1996

Duke University

M.D. 2000

University of Virginia School of Medicine

M.Sc. 2008

Johns Hopkins University

Internship/Residency, General Internal Medicine

University of Pennsylvania, School of Medicine

Fellowship, Division Of Oncology/Hematology

Johns Hopkins University School of Medicine

Grants:

Study title: A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Study of Olaparib Plus Abiraterone Relative to Placebo Plus Abiraterone as First-line Therapy in Men with Metastatic Castration-resistant Prostate Cancer

Administered By
Duke Cancer Institute
Awarded By
AstraZeneca AB
Role
Principal Investigator
Start Date
End Date

ProSTAR: A Phase 1b/2 Study of CPI-1205, a Small Molecule Inhibitor of EZH2, Combined with Enzalutamide or Abiraterone/Prednisone in Patients with Metastatic Castration Resistant Prostate Cancer

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

VISION: An International, Prospective, Open-Label, Multicenter, Randomized Phase 3 Study of 177lu-Psma-617 in the Treatment of Patients with Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Administered By
Duke Cancer Institute
Awarded By
Endocyte, Inc.
Role
Principal Investigator
Start Date
End Date

A Phase 2 Study of Nivolumab in combination with either Rucaparib, docetaxel, or enzalutamide in men with Castration-resistant metastaic prostate cancer (CheckMate 9KD: CHECKpoint pathway and nivoluMA

Administered By
Duke Cancer Institute
Awarded By
Bristol-Myers Squibb Company
Role
Principal Investigator
Start Date
End Date

A Phase II Study of Navarixin (MK-7123) in Combination with Pembrolizumab (MK-3475) in Participants with Selected Advanced/Metastatic Solid Tumors

Administered By
Duke Cancer Institute
Awarded By
Merck Sharp & Dohme
Role
Principal Investigator
Start Date
End Date

Publications:

Prostate-specific membrane antigen-targeted theranostics: past, present, and future approaches.

Although prostate cancer is the type of cancer most commonly survived by men in the United States, it remains the second most common cause of death from cancer, largely owing to metastatic disease. Patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease has progressed on standard-of-care therapies have few options and a poor prognosis. Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein that is commonly expressed in prostate cancer. Expression is limited on extra-prostatic tissues other than the salivary glands, lacrimal glands, duodenal epithelium, Kupffer cells, and renal tubules. PSMA-directed theranostics has emerged to exploit the specificity of PSMA for prostate cancer cells and has demonstrated promising results in the clinic. Radionuclides linked to PSMA inhibitors/binders have resulted in US Food and Drug Administration (FDA) approval of 2 radiodiagnostics for PSMA-directed positron emission tomography/computed tomography. In addition, these radionuclides have led to the development of lutetium Lu 177PSMA-617 therapy, which is currently under priority FDA review. Multiple novel PSMA-targeted modalities have been developed and are currently under clinical investigation, including ligand-drug and cellular immune therapies. In this review, we discuss the development of PSMA-directed theranostics, along with its clinical implications, limitations, and future directions.
Authors
Hawkey, NM; Sartor, AO; Morris, MJ; Armstrong, AJ
MLA Citation
Hawkey, Nathan M., et al. “Prostate-specific membrane antigen-targeted theranostics: past, present, and future approaches.Clin Adv Hematol Oncol, vol. 20, no. 4, Apr. 2022, pp. 227–38.
URI
https://scholars.duke.edu/individual/pub1515643
PMID
35389387
Source
pubmed
Published In
Clinical Advances in Hematology & Oncology : H&O
Volume
20
Published Date
Start Page
227
End Page
238

Bimodal liquid biopsy for cancer immunotherapy based on peptide engineering and nanoscale analysis.

Despite its high potential, PD-L1 expressed by tumors has not been successfully utilized as a biomarker for estimating treatment responses to immunotherapy. Circulating tumor cells (CTCs) and tumor-derived exosomes that express PD-L1 can potentially be used as biomarkers; however, currently available assays lack clinically significant sensitivity and specificity. Here, a novel peptide-based capture surface is developed to effectively isolate PD-L1-expressing CTCs and exosomes from human blood. For the effective targeting of PD-L1, this study integrates peptide engineering strategies to enhance the binding strength and specificity of a β-hairpin peptide derived from PD-1 (pPD-1). Specifically, this study examines the effect of poly(ethylene glycol) spacers, the secondary peptide structure, and modification of peptide sequences (e.g., removal of biologically redundant amino acid residues) on capture efficiency. The optimized pPD-1 configuration captures PD-L1-expressing tumor cells and tumor-derived exosomes with 1.5-fold (p = 0.016) and 1.2-fold (p = 0.037) higher efficiencies, respectively, than their whole antibody counterpart (aPD-L1). This enhanced efficiency is translated into more clinically significant detection of CTCs (1.9-fold increase; p = 0.035) and exosomes (1.5-fold increase; p = 0.047) from patients' baseline samples, demonstrating stronger correlation with patients' treatment responses. Additionally, we confirmed that the clinical accuracy of our system can be further improved by co-analyzing the two biomarkers (bimodal CTC/exosome analysis). These data demonstrate that pPD-1-based capture is a promising approach for capturing PD-L1-expressing CTCs and exosomes, which can be used as a reliable biomarker for cancer immunotherapy.
Authors
Bu, J; Jeong, W-J; Jafari, R; Kubiatowicz, LJ; Nair, A; Poellmann, MJ; Hong, RS; Liu, EW; Owen, RH; Rawding, PA; Hopkins, CM; Kim, D; George, DJ; Armstrong, AJ; Král, P; Wang, AZ; Bruce, J; Zhang, T; Kimple, RJ; Hong, S
MLA Citation
Bu, Jiyoon, et al. “Bimodal liquid biopsy for cancer immunotherapy based on peptide engineering and nanoscale analysis.Biosens Bioelectron, vol. 213, Oct. 2022, p. 114445. Pubmed, doi:10.1016/j.bios.2022.114445.
URI
https://scholars.duke.edu/individual/pub1524076
PMID
35679646
Source
pubmed
Published In
Biosens Bioelectron
Volume
213
Published Date
Start Page
114445
DOI
10.1016/j.bios.2022.114445

Highlights in advanced prostate cancer from the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium: commentary.

Authors
MLA Citation
Armstrong, Andrew J. “Highlights in advanced prostate cancer from the 2022 American Society of Clinical Oncology Genitourinary Cancers Symposium: commentary.Clin Adv Hematol Oncol, vol. 20 Suppl 8, no. 4, Apr. 2022, pp. 16–22.
URI
https://scholars.duke.edu/individual/pub1521840
PMID
35579593
Source
pubmed
Published In
Clinical Advances in Hematology & Oncology : H&O
Volume
20 Suppl 8
Published Date
Start Page
16
End Page
22

Editor' summary: A paradigm shift in castration-resistant prostate cancer management.

Authors
De Nunzio, C; Amstrong, AJ; Van Oort, I; Dorff, T
MLA Citation
De Nunzio, Cosimo, et al. “Editor' summary: A paradigm shift in castration-resistant prostate cancer management.Prostate Cancer Prostatic Dis, July 2022. Pubmed, doi:10.1038/s41391-022-00574-x.
URI
https://scholars.duke.edu/individual/pub1529660
PMID
35840723
Source
pubmed
Published In
Prostate Cancer Prostatic Dis
Published Date
DOI
10.1038/s41391-022-00574-x

A phase 2 trial of avelumab in men with aggressive-variant or neuroendocrine prostate cancer.

BACKGROUND: Men with progressive neuroendocrine or aggressive-variant metastatic prostate cancer (NEPC/AVPC) have a poor prognosis and limited treatment options, and immunotherapy has not been tested in such patients. METHODS: We conducted an open label single center phase 2 trial (NCT03179410) of men with progressive NEPC/AVPC either defined by histology or AVPC criteria. Avelumab (10 mg/kg every 2 weeks) was administered until progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Secondary endpoints included ORR, radiographic progression-free survival (rPFS), overall survival, and safety. Correlative studies included longitudinal peripheral blood immune phenotyping. The study was limited by the small number of patients enrolled and by the early termination due to COVID-19. RESULTS: A total of 15 men with AVPC/NEPC were enrolled. The median age was 71 (range 51-85 years), and men had received a median of two prior therapies (range 1-3). Median PSA was 54 ng/dl (range 0-393), and 73% of men had liver metastasis. The ORR with avelumab in this setting by iRECIST or RECIST 1.1 was 6.7%, including one patient (6.7%) with a complete remission (CR), 20% with stable disease, and 67% with progressive disease. The patient with the CR had an MSH2 somatic mutation and MSI-high NEPC with central nervous system metastases, and his CR remains durable off all therapy for 2 years. The median rPFS was 1.8 months (95% CI 1.6-3.6 months), and median overall survival was 7.4 months (85% CI 2.8-12.6 months). Safety was consistent with the known profile of avelumab. Phenotyping of peripheral immune subsets suggest enhanced CXCR2-dependent myeloid and T-cell responses in this extraordinary responder. CONCLUSIONS: While the study was terminated early due to slow enrollment at the onset of the COVID-19 pandemic and lower than anticipated objective response rate, PD-L1 inhibition with avelumab monotherapy showed poor efficacy in patients with microsatellite stable NEPC/AVPC. Immune profiling revealed enhanced CXCR2 positive immune cell activation in the one extraordinary responder, suggesting potential mechanisms for further immunotherapy development in this population.
Authors
Brown, LC; Halabi, S; Somarelli, JA; Humeniuk, M; Wu, Y; Oyekunle, T; Howard, L; Huang, J; Anand, M; Davies, C; Patel, P; Staats, J; Weinhold, KJ; Harrison, MR; Zhang, T; George, DJ; Armstrong, AJ
MLA Citation
Brown, Landon C., et al. “A phase 2 trial of avelumab in men with aggressive-variant or neuroendocrine prostate cancer.Prostate Cancer Prostatic Dis, Mar. 2022. Pubmed, doi:10.1038/s41391-022-00524-7.
URI
https://scholars.duke.edu/individual/pub1512693
PMID
35292724
Source
pubmed
Published In
Prostate Cancer Prostatic Dis
Published Date
DOI
10.1038/s41391-022-00524-7