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:

A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer.

<h4>Purpose</h4>Men with metastatic castration-resistant prostate cancer (mCRPC) have limited treatment options after progressing on hormonal therapy and chemotherapy. Here, we evaluate the safety and efficacy of atezolizumab (anti-PD-L1) + radium-223 dichloride (radium-223) in men with mCRPC.<h4>Patients and methods</h4>This phase Ib study evaluated atezolizumab + radium-223 in men with mCRPC and bone and lymph node and/or visceral metastases that progressed after androgen pathway inhibitor treatment. Following safety assessment of concurrent dosing, 45 men were randomized 1:1:1 to concurrent or one of two staggered dosing schedules with either agent introduced one cycle before the other. This was followed by a safety-efficacy expansion cohort (randomized 1:1:1). The primary endpoints were safety and objective response rate (ORR) by RECIST 1.1. Secondary endpoints included radiographic progression-free survival (rPFS), PSA responses, and overall survival (OS).<h4>Results</h4>As of October 4, 2019, 44 of 45 men were evaluable. All 44 had ≥1 all-cause adverse event (AE); 23 (52.3%) had a grade 3/4 AE. Fifteen (34.1%) grade 3/4 and 3 (6.8%) grade 5 AEs were related to atezolizumab; none were related to radium-223. Confirmed ORR was 6.8% [95% confidence interval (CI), 1.4-18.7], median rPFS was 3.0 months (95% CI, 2.8-4.6), median PSA progression was 3.0 months (95% CI, 2.8-3.3), and median OS was 16.3 months (95% CI, 10.9-22.3).<h4>Conclusions</h4>This phase Ib study demonstrated that atezolizumab + radium-223, regardless of administration schedule, had greater toxicity than either drug alone, with no clear evidence of additional clinical benefit for patients with mCRPC and bone and lymph node and/or visceral metastases.
Authors
Fong, L; Morris, MJ; Sartor, O; Higano, CS; Pagliaro, L; Alva, A; Appleman, LJ; Tan, W; Vaishampayan, U; Porcu, R; Tayama, D; Kadel, EE; Yuen, KC; Datye, A; Armstrong, AJ; Petrylak, DP
MLA Citation
Fong, Lawrence, et al. “A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer.Clinical Cancer Research : An Official Journal of the American Association for Cancer Research, vol. 27, no. 17, Sept. 2021, pp. 4746–56. Epmc, doi:10.1158/1078-0432.ccr-21-0063.
URI
https://scholars.duke.edu/individual/pub1484975
PMID
34108181
Source
epmc
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
27
Published Date
Start Page
4746
End Page
4756
DOI
10.1158/1078-0432.ccr-21-0063

579MO CheckMate 9KD cohort A2 final analysis: Nivolumab (NIVO) + rucaparib for chemotherapy (CT)-naïve metastatic castration-resistant prostate cancer (mCRPC)

Authors
Petrylak, DP; Perez-Gracia, JL; Lacombe, L; Bastos, DA; Mahammedi, H; Kwan, EM; Zschäbitz, S; Armstrong, AJ; Pachynski, RK; Goh, JC; Burotto, M; Gravis, G; McCune, SL; Vázquez Limón, JC; Retz, M; Saad, F; Amin, NP; Li, J; Unsal-Kacmaz, K; Fizazi, K
MLA Citation
Petrylak, D. P., et al. “579MO CheckMate 9KD cohort A2 final analysis: Nivolumab (NIVO) + rucaparib for chemotherapy (CT)-naïve metastatic castration-resistant prostate cancer (mCRPC).” Annals of Oncology, vol. 32, Elsevier BV, 2021, pp. S629–30. Crossref, doi:10.1016/j.annonc.2021.08.1092.
URI
https://scholars.duke.edu/individual/pub1498324
Source
crossref
Published In
Annals of Oncology
Volume
32
Published Date
Start Page
S629
End Page
S630
DOI
10.1016/j.annonc.2021.08.1092

Analysis of immune subtypes across the epithelial-mesenchymal plasticity spectrum.

Epithelial-mesenchymal plasticity plays a critical role in many solid tumor types as a mediator of metastatic dissemination and treatment resistance. In addition, there is also a growing appreciation that the epithelial/mesenchymal status of a tumor plays a role in immune evasion and immune suppression. A deeper understanding of the immunological features of different tumor types has been facilitated by the availability of large gene expression datasets and the development of methods to deconvolute bulk RNA-Seq data. These resources have generated powerful new ways of characterizing tumors, including classification of immune subtypes based on differential expression of immunological genes. In the present work, we combine scoring algorithms to quantify epithelial-mesenchymal plasticity with immune subtype analysis to understand the relationship between epithelial plasticity and immune subtype across cancers. We find heterogeneity of epithelial-mesenchymal transition (EMT) status both within and between cancer types, with greater heterogeneity in the expression of EMT-related factors than of MET-related factors. We also find that specific immune subtypes have associated EMT scores and differential expression of immune checkpoint markers.
Authors
Chakraborty, P; Chen, EL; McMullen, I; Armstrong, AJ; Kumar Jolly, M; Somarelli, JA
MLA Citation
Chakraborty, Priyanka, et al. “Analysis of immune subtypes across the epithelial-mesenchymal plasticity spectrum.Comput Struct Biotechnol J, vol. 19, 2021, pp. 3842–51. Pubmed, doi:10.1016/j.csbj.2021.06.023.
URI
https://scholars.duke.edu/individual/pub1489075
PMID
34306571
Source
pubmed
Published In
Computational and Structural Biotechnology Journal
Volume
19
Published Date
Start Page
3842
End Page
3851
DOI
10.1016/j.csbj.2021.06.023

LBA25 Final overall survival (OS) analysis from ARCHES: A phase III, randomized, double-blind, placebo (PBO)-controlled study of enzalutamide (ENZA) + androgen deprivation therapy (ADT) in men with metastatic hormone-sensitive prostate cancer (mHSPC)

Authors
Armstrong, AJ; Iguchi, T; Azad, AA; Szmulewitz, RZ; Holzbeierlein, J; Villers, A; Alcaraz, A; Alekseev, BY; Shore, ND; Petrylak, DP; Rosbrook, B; Zohren, F; Yamada, S; Haas, GP; Stenzl, A
URI
https://scholars.duke.edu/individual/pub1498708
Source
crossref
Published In
Annals of Oncology
Volume
32
Published Date
Start Page
S1300
End Page
S1301
DOI
10.1016/j.annonc.2021.08.2101

Efficacy of enzalutamide in subgroups of men with metastatic hormone-sensitive prostate cancer based on prior therapy, disease volume, and risk.

BACKGROUND: While enzalutamide plus androgen deprivation therapy (ADT) significantly reduces the risk of radiographic progression-free survival (rPFS) and improves overall survival in metastatic hormone-sensitive prostate cancer (mHSPC), the efficacy in clinically relevant subgroups of patients based on prior local and systemic therapy, disease volume, and risk has not been analyzed to date. These post hoc analyses of the phase 3 ARCHES trial (NCT02677896) evaluated the efficacy of enzalutamide plus ADT according to prior local and systemic treatment, disease volume, and risk, assessed at trial baseline. METHODS: In ARCHES, a global, double-blind, placebo-controlled, phase 3 study, 1150 patients with mHSPC were randomized 1:1 to receive enzalutamide (160 mg/day) plus ADT or placebo plus ADT, stratified by prior docetaxel therapy and disease volume. Primary endpoint was rPFS. Secondary endpoints included time to prostate-specific antigen progression, symptomatic skeletal events, and prostate-specific antigen and radiographic responses. Analyses of clinical endpoints were completed by prior local therapy, prior docetaxel exposure, CHAARTED (NCT00309985)-defined disease volume, and LATITUDE (NCT01715285)-defined risk groups. RESULTS: Patients were randomized to enzalutamide plus ADT (n = 574) and placebo plus ADT (n = 576). Enzalutamide plus ADT significantly improved rPFS (hazard ratio: 0.39; p < 0.0001), with similar improvements reported in all subgroups based on prior local and docetaxel treatment, disease volume, and risk. Treatment benefits were observed with enzalutamide plus ADT in multiple secondary clinical endpoints in the overall population and all subgroups. CONCLUSIONS: Enzalutamide plus ADT demonstrated clinical benefit across all patients with mHSPC, irrespective of prior local and systemic treatment, disease volume, and risk.
Authors
Azad, AA; Armstrong, AJ; Alcaraz, A; Szmulewitz, RZ; Petrylak, DP; Holzbeierlein, J; Villers, A; Alekseev, B; Iguchi, T; Shore, ND; Gomez-Veiga, F; Rosbrook, B; Lee, H-J; Haas, GP; Stenzl, A
MLA Citation
Azad, Arun A., et al. “Efficacy of enzalutamide in subgroups of men with metastatic hormone-sensitive prostate cancer based on prior therapy, disease volume, and risk.Prostate Cancer Prostatic Dis, Aug. 2021. Pubmed, doi:10.1038/s41391-021-00436-y.
URI
https://scholars.duke.edu/individual/pub1494387
PMID
34420037
Source
pubmed
Published In
Prostate Cancer Prostatic Dis
Published Date
DOI
10.1038/s41391-021-00436-y