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

Associate Professor in Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Professor in Surgery

Surgery, Urology
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:

Severe-COVID-19 and mortality among patients (pts) with prostate cancer (PCa) receiving androgen deprivation therapy (ADT).

<jats:p> 39 </jats:p><jats:p> Background: The presence of progressing cancer, male sex and advanced age have been shown to increase the severity of coronavirus disease 2019 (COVID-19). Given that the androgen regulated gene TMPRSS2 has been implicated in SARS-CoV-2 viral entry, we hypothesized that ADT may improve COVID-19 outcomes. This analysis evaluated clinical outcomes of pts with PCa with concurrent SARS-CoV-2 infection and investigated the impact of ADT on occurrence of severe-COVID-19 and mortality. Methods: Data was obtained via the COVID-19 and Cancer Consortium (CCC19), a multicenter registry including &gt;120 cancer centers with de-identified data from pts with COVID-19 and cancer. Men with confirmed SARS-CoV-2 infection and a primary diagnosis of prostate cancer were included: data cutoff of July 31, 2020. The primary endpoint was the development of severe-COVID-19 (death, ICU admission, or mechanical ventilation) among pts on ADT vs. those not on ADT at time of COVID-19 infection. Secondary endpoints included 30-day mortality based on ADT use. Mortality and development of severe-COVID-19 were assessed in Pts grouped by therapy: 1st generation androgen receptor inhibitor (ARI-1), 2nd generation ARI (darolutamide, enzalutamide, apalutamide, ARI-2), abiraterone/prednisone, and chemotherapy. Propensity score matching was utilized. Logistic regression was utilized to adjust for age, ECOG PS, comorbidities, and race. Results: 589 pts were included; median follow-up was 42 days (IQR 25-90) and 62% (363/589) were hospitalized. Severe-COVID-19 developed in 28% of pts and the all-cause 30-day mortality rate was 19%. There was no significant difference in the development of severe-COVID-19 or 30-day mortality between Pts on ADT vs not on ADT, whether using descriptive statistics with the entire population or using the propensity score matched population (Table). Among the descriptive population, the numerical rates of severe-COVID-19 and mortality were lowest in Pts receiving ARI-2, but sample size was low. Conclusions: The overall 30-day mortality rate and percentage developing severe-COVID-19 were high. There was no statistical difference in the development of severe-COVID-19 or mortality based on receipt of ADT; however, this analysis is limited by the retrospective nature and small N after propensity-matching. [Table: see text] </jats:p>
Authors
Tucker, MD; Schmidt, AL; Hsu, C-Y; Shyr, Y; Armstrong, AJ; Bakouny, Z; Chapman, CH; Dawsey, S; Gartrell, BA; Halabi, S; Joshi, M; Khaki, AR; Menon, H; Puc, M; Sharifi, N; Shaya, J; Wulff-Burchfield, EM; Zhang, T; Gupta, S; McKay, RR
MLA Citation
Tucker, Matthew D., et al. “Severe-COVID-19 and mortality among patients (pts) with prostate cancer (PCa) receiving androgen deprivation therapy (ADT).Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 39–39. Crossref, doi:10.1200/jco.2021.39.6_suppl.39.
URI
https://scholars.duke.edu/individual/pub1480330
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
39
End Page
39
DOI
10.1200/jco.2021.39.6_suppl.39

CheckMate 9KD Arm B final analysis: Efficacy and safety of nivolumab plus docetaxel for chemotherapy-naïve metastatic castration-resistant prostate cancer.

<jats:p> 12 </jats:p><jats:p> Background: CheckMate 9KD (NCT03338790) is a phase 2 trial of nivolumab (NIVO; anti-PD-1) in combination with rucaparib, docetaxel (DOCE), or enzalutamide for patients with metastatic castration-resistant prostate cancer (mCRPC). DOCE is a standard-of-care chemotherapy for mCRPC that may potentiate antitumor immune responses, thus supporting its use in combination with NIVO, which has shown limited antitumor activity in mCRPC as monotherapy. We report final analysis results for Arm B (NIVO + DOCE) of CheckMate 9KD. Methods: Arm B enrolled patients with chemotherapy-naive mCRPC with ongoing androgen deprivation therapy and ≤ 2 prior novel antiandrogen therapies (NATs; i.e., abiraterone, enzalutamide, etc.). Patients received NIVO 360 mg + DOCE 75 mg/m<jats:sup>2</jats:sup> Q3W + prednisone 5 mg BID for ≤ 10 cycles, followed by NIVO 480 mg Q4W until disease progression/unacceptable toxicity (up to 2 years). Coprimary endpoints were objective response rate (ORR) and prostate-specific antigen response rate (PSA-RR; defined as a ≥ 50% PSA reduction). Secondary endpoints included radiographic progression-free survival (rPFS), overall survival (OS), and safety. Results: Of 84 treated patients with a median age of 71 years (range: 53-88), 27% had visceral disease and 54% had measurable disease. The median number of docetaxel cycles was 8; the median number of nivolumab doses was 11. Median follow up was 15.2 months. The table displays the efficacy outcomes, which appear to show comparable ORR in patients receiving versus not receiving prior NAT. There was 1 (2.2%) complete objective response and 17 (37.8%) partial responses in 45 patients with measurable disease. Any-grade treatment-related AEs (TRAEs) occurred in 95.2% of patients, most commonly fatigue (39.3%), diarrhea (35.7%), and alopecia (34.5%). Grade 3-4 TRAEs occurred in 47.6% of patients, most commonly neutropenia (16.7%). TRAEs led to discontinuation in 29.8% of patients. The most common immune-related AEs were GI (35.7%) or skin-related (26.2%). There were 3 treatment-related deaths (1 pneumonitis related to NIVO; 2 pneumonias related to DOCE). Conclusions: NIVO + DOCE has encouraging clinical activity in patients with chemotherapy-naïve mCRPC, regardless of prior NAT, with a safety profile consistent with those of the individual agents. These outcomes support the ongoing phase 3 CheckMate 7DX trial of NIVO + DOCE vs placebo + DOCE for mCRPC (NCT04100018). Clinical trial information: NCT03338790. [Table: see text] </jats:p>
Authors
Fizazi, K; González Mella, P; Castellano, D; Minatta, JN; Rezazadeh, A; Shaffer, DR; Vazquez Limon, JC; Sánchez López, HM; Armstrong, AJ; Horvath, L; Dzik, C; Amin, NP; Li, J; Unsal-Kacmaz, K; Retz, M; Saad, F; Petrylak, DP; Pachynski, RK
MLA Citation
Fizazi, Karim, et al. “CheckMate 9KD Arm B final analysis: Efficacy and safety of nivolumab plus docetaxel for chemotherapy-naïve metastatic castration-resistant prostate cancer.Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 12–12. Crossref, doi:10.1200/jco.2021.39.6_suppl.12.
URI
https://scholars.duke.edu/individual/pub1480456
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
12
End Page
12
DOI
10.1200/jco.2021.39.6_suppl.12

Development and validation of circulating tumour cell enumeration (Epic Sciences) as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.

PURPOSE: To evaluate the prognostic significance of circulating tumour cell (CTC) number determined on the Epic Sciences platform in men with metastatic castration-resistant prostate cancer (mCRPC) treated with an androgen receptor signalling inhibitor (ARSI). PATIENTS AND METHODS: A pre-treatment blood sample was collected from men with progressing mCRPC starting either abiraterone or enzalutamide as a first-, second- or third-line systemic therapy at Memorial Sloan Kettering Cancer Center (Discovery cohort, N = 171) or as a first- or second-line therapy as part of the multicenter PROPHECY trial (NCT02269982) (Validation cohort, N = 107). The measured CTC number was then associated with overall survival (OS) in the Discovery cohort, and progression-free survival (PFS) and OS in the Validation cohort. CTC enumeration was also performed on a concurrently obtained blood sample using the CellSearch® Circulating Tumor Cell Kit. RESULTS: In the MSKCC Discovery cohort, CTC count was a statistically significant prognostic factor of OS as a dichotomous (<3 CTCs/mL versus ≥ 3 CTCs/mL; hazard ratio [HR] = 1.8 [95% confidence interval {CI} 1.3-3.0]) and a continuous variable when adjusting for line of therapy, presence of visceral metastases, prostate-specific antigen, lactate dehydrogenase and alkaline phosphatase. The findings were validated in an independent datas et from PROPHECY (HR [95% CI] = 1.8 [1.1-3.0] for OS and 1.7 [1.1-2.9] for PFS). A strong correlation was also observed between CTC counts determined in matched samples on the CellSearch® and Epic platforms (r = 0.84). CONCLUSION: The findings validate the prognostic significance of pretreatment CTC number determined on the Epic Sciences platform for predicting OS in men with progressing mCRPC starting an ARSI.
Authors
Scher, HI; Armstrong, AJ; Schonhoft, JD; Gill, A; Zhao, JL; Barnett, E; Carbone, E; Lu, J; Antonarakis, ES; Luo, J; Tagawa, S; Dos Anjos, CH; Yang, Q; George, D; Szmulewitz, R; Danila, DC; Wenstrup, R; Gonen, M; Halabi, S
MLA Citation
Scher, H. I., et al. “Development and validation of circulating tumour cell enumeration (Epic Sciences) as a prognostic biomarker in men with metastatic castration-resistant prostate cancer.Eur J Cancer, vol. 150, Apr. 2021, pp. 83–94. Pubmed, doi:10.1016/j.ejca.2021.02.042.
URI
https://scholars.duke.edu/individual/pub1480561
PMID
33894633
Source
pubmed
Published In
Eur J Cancer
Volume
150
Published Date
Start Page
83
End Page
94
DOI
10.1016/j.ejca.2021.02.042

Phase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC).

<jats:p> TPS183 </jats:p><jats:p> Background: Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a cell surface antigen that is highly expressed in prostate cancer. AMG 509 is a potent bispecific XmAb 2+1 immune therapy designed to direct T effector cells to STEAP1-expressing cells. AMG 509 contains two identical humanized anti-STEAP1 Fab domains that bind STEAP1-expressing cells, an anti-CD3 scFv domain that binds T cells, and an Fc domain, engineered to lack effector function, that extends serum half-life. In preclinical studies, AMG 509 induced potent and specific T-cell-mediated lysis of STEAP1-expressing cancer models. Methods: This open-label, phase 1, first-in-human study will evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 509 in patients with relapsed/refractory mCRPC. The dose exploration phase (n=40) will estimate the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) using a Bayesian logistic regression model. The dose expansion phase (n=30) will confirm safety, PK, and pharmacodynamics at the MTD or RP2D and collect further safety, efficacy, and biomarker data. Efficacy will be assessed by prostate-specific antigen response, circulating tumor cell response, and objective tumor response per RECIST 1.1 with Prostate Cancer Working Group 3 modifications. Key inclusion criteria: men ≥18 years with histologically/cytologically confirmed mCRPC who are refractory to novel hormonal therapy (e.g., abiraterone and/or enzalutamide) and have failed 1–2 taxane regimens or are medically unsuitable for or have refused taxanes; ongoing castration with total serum testosterone ≤50 ng/dL; evidence of progressive disease; ECOG performance status 0–1; life expectancy ≥3 months; and adequate hematologic, renal, hepatic, and cardiac function. In the dose exploration phase, novel antiandrogen therapy must have been given in the metastatic setting. Key exclusion criteria: pure small cell or neuroendocrine carcinoma of the prostate; untreated CNS metastases or leptomeningeal disease; any anticancer therapy or immunotherapy, radiation therapy, or major surgery &lt;4 weeks from first dose; history of or current autoimmune disease or any disease requiring immunosuppressive therapy (≤10 mg/d prednisone permitted); prior STEAP1-targeted therapy; infection requiring IV antimicrobials &lt;7 days from first dose. The study opened in January 2020 and is recruiting patients. ClinicalTrials.gov: NCT04221542. 2020 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2020 ASCO Annual Meeting. All rights reserved. Clinical trial information: NCT04221542. </jats:p>
Authors
Kelly, WK; Pook, DW; Appleman, LJ; Waterhouse, DM; Horvath, L; Edenfield, WJ; Matsubara, N; Danila, DC; Aggarwal, RR; Petrylak, DP; Sartor, AO; Sumey, CJ; Adra, N; Armstrong, AJ; Cheng, F-C; Stieglmaier, J; Kouros-Mehr, H; Dorff, TB
MLA Citation
Kelly, William Kevin, et al. “Phase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC).Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. TPS183–TPS183. Crossref, doi:10.1200/jco.2021.39.6_suppl.tps183.
URI
https://scholars.duke.edu/individual/pub1481071
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
TPS183
End Page
TPS183
DOI
10.1200/jco.2021.39.6_suppl.tps183

Interim analysis of STARTAR: A phase II salvage trial of androgen receptor (AR) inhibition with androgen deprivation therapy (ADT) and apalutamide with radiation therapy (RT) followed by docetaxel in men with PSA recurrent prostate cancer (PC) after radic

<jats:p> 90 </jats:p><jats:p> Background: ADT with salvage RT improves survival for men with PSA recurrence after RP. Current standard duration of ADT for high risk PSA recurrence is up to 2 years with RT; therefore shortening but intensifying systemic therapy may improve outcomes. The STREAM trial showed 6 mo of enzalutamide added to ADT/RT had a 3-year progression free survival (PFS) of 53% in high risk patients including lymph node (LN) positive. Given that docetaxel improves survival in men with mHSPC, we evaluated the combination of salvage RT, ADT/apalutamide and docetaxel in this setting. Methods: STARTAR is a multicenter phase 2 trial for salvage treatment of PSA recurrent PC following RP conducted within the US Dept. of Defense Prostate Cancer Clinical Trials Consortium (DOD PCCTC). Key inclusion criteria included PC with Gleason 7 with T3/positive margin/1-4 positive LNs or Gleason 8-10 disease and PSA relapse within 4 years of RP (min PSA 0.2 ng/mL to max PSA 4 ng/mL). Men with up to 4 positive resected LNs were eligible. Men started ADT with apalutamide, continued with RT (66-74 Gy to the prostate bed +/- pelvic LNs over 6-8 weeks), and finally completed docetaxel 75mg/m2 IV q3 weeks for 6 cycles. Men were treated with ADT and apalutamide for approximately 9 months. The primary endpoint was PSA PFS at 36 months. This interim analysis evaluated secondary endpoints of 1-year PSA recurrence, testosterone recovery, and safety of this treatment sequence. Results: From 3/2018 to 12/2019, 39 men were enrolled at Duke, Wake Forest, Cornell, and the GU Research Network. With a data cutoff in 9/2020, median follow up from enrollment was 14 months. Baseline patient characteristics included Gleason 4+3 = 7 in 54% and Gleason 8-10 in 46%, and 23% LN positive; median PSA at the time of enrollment was 0.58 ng/mL (range 0.21-3.40) and the median time from RP to enrollment was 7 mo (range 2-98). At 1 year, there have been no progression events with 38% (12/31) of men with post-treatment testosterone recovery into normal range (recovery time median 10 mos [1-17 mos]). Common adverse events (AEs) of any-grade at least possibly related to the regimen were 98% hot flashes, 88% fatigue, 77% alopecia, 57% dysgeusia, and 53% rash (28% grade 1; 15% grade 2, 10% grade 3), with neutropenia as the most common grade 3/4 AE (27/39 men, 70%) with two grade 3 febrile neutropenia. Conclusions: In this first phase 2 trial of ADT, apalutamide, radiation, and 6 cycles docetaxel in the salvage setting for high risk PSA recurrence, short term outcomes are excellent with no recurrences at 12 months of follow-up. This salvage treatment was well tolerated in the majority of men with the exception of a high rate of drug rashes and neutropenia related to the course of treatment, in line with known safety profiles of the study agents. Clinical trial information: NCT03311555. </jats:p>
Authors
Zhang, T; Koontz, BF; Tagawa, ST; Nagar, H; Bitting, RL; Frizzell, B; Nordquist, LT; Rasmussen, J; Wilder, R; Anand, M; Winters, C; Riggan, C; Fernandez, E; Healy, P; Oyekunle, T; Wu, Y; McNamara, MA; Harrison, MR; George, DJ; Armstrong, AJ
MLA Citation
Zhang, Tian, et al. “Interim analysis of STARTAR: A phase II salvage trial of androgen receptor (AR) inhibition with androgen deprivation therapy (ADT) and apalutamide with radiation therapy (RT) followed by docetaxel in men with PSA recurrent prostate cancer (PC) after radical prostatectomy (RP).Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 90–90. Crossref, doi:10.1200/jco.2021.39.6_suppl.90.
URI
https://scholars.duke.edu/individual/pub1480286
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
90
End Page
90
DOI
10.1200/jco.2021.39.6_suppl.90