Hope Uronis

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. 2000

State University of New York - Buffalo

Medical Resident, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Chief Medical Resident -Duke Hospital, Medicine

Duke University

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

A Phase III, Randomized, Double-blind Trial Comparing Trastuzumab Plus Chemotherapy and Pembrolizumab With Trastuzumab Plus Chemotherapy and Placebo asFirst-line Treatment in Participants With HER2 Positive Advanced Gastric or Gastroesophageal Juncti

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

A Randomized multicenter double blind Phase III study of Nivolumab or placebo in subjects with resected esophageal junction cancer.

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

A Multicenter randomized open label study in patients with esophageal cancer refractory or intorlerant to combination therapy with fluoropyrimidine

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

A Phase 1b/2 open label dose escalation study of Margetuximab incombination with Pembrolizumab in patients with relapsed refrectory advanced HER2 + Gastroesophageal junction or gastric cancer.

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

Key-LARGO: A Single Arm, Phase II Study of Pembrolizumab, Oxaliplatin, and Capecitabine in the First Line Treatment of Patients with Gastro-esophageal Cancer,"

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

Publications:

Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22-05): a single-arm, phase 1b-2 trial.

BACKGROUND: Margetuximab, a novel, investigational, Fc-engineered, anti-HER2 monoclonal antibody, is designed to more effectively potentiate innate immunity than trastuzumab. We aimed to evaluate the safety, tolerability, and antitumour activity of margetuximab plus pembrolizumab (an anti-PD-1 monoclonal antibody) in previously treated patients with HER2-positive gastro-oesophageal adenocarcinoma. METHODS: CP-MGAH22-05 was a single-arm, open-label, phase 1b-2 dose-escalation and cohort expansion study done at 11 academic centres in the USA and Canada and 15 centres in southeast Asia (Korea, Taiwan, and Singapore) that enrolled men and women aged 18 years or older with histologically proven, unresectable, locally advanced or metastatic, HER2-positive, PD-L1-unselected gastro-oesophageal adenocarcinoma, with an Eastern Cooperative Oncology Group performance status of 0 or 1, who had progressed after at least one previous line of therapy with trastuzumab plus chemotherapy in the locally advanced unresectable or metastatic setting. In the dose-escalation phase, nine patients were treated: three received margetuximab 10 mg/kg intravenously plus pembrolizumab 200 mg intravenously every 3 weeks and six received the recommended phase 2 dose of margetuximab 15 mg/kg plus pembrolizumab 200 mg intravenously every 3 weeks. An additional 86 patients were enrolled in the phase 2 cohort expansion and received the recommended phase 2 dose. The primary endpoints were safety and tolerability, assessed in the safety population (patients who received at least one dose of either margetuximab or pembrolizumab) and the objective response rate as assessed by the investigator according to both Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, in the response-evaluable population (patients with measurable disease at baseline and who received the recommended phase 2 dose of margetuximab and pembrolizumab). This trial is registered with ClinicalTrials.gov, NCT02689284. Recruitment for the trial has completed and follow-up is ongoing. FINDINGS: Between Feb 11, 2016, and Oct 2, 2018, 95 patients were enrolled. Median follow-up was 19·9 months (IQR 10·7-23·1). The combination therapy showed acceptable safety and tolerability; there were no dose-limiting toxicities in the dose-escalation phase. The most common grade 3-4 treatment-related adverse events were anaemia (four [4%]) and infusion-related reactions (three [3%]). Serious treatment-related adverse events were reported in nine (9%) patients. No treatment-related deaths were reported. Objective responses were observed in 17 (18·48%; 95% CI 11·15-27·93) of 92 evaluable patients. INTERPRETATION: These findings serve as proof of concept of synergistic antitumour activity with the combination of an Fc-optimised anti-HER2 agent (margetuximab) along with anti-PD-1 checkpoint blockade (pembrolizumab). FUNDING: MacroGenics.
Authors
Catenacci, DVT; Kang, Y-K; Park, H; Uronis, HE; Lee, K-W; Ng, MCH; Enzinger, PC; Park, SH; Gold, PJ; Lacy, J; Hochster, HS; Oh, SC; Kim, YH; Marrone, KA; Kelly, RJ; Juergens, RA; Kim, JG; Bendell, JC; Alcindor, T; Sym, SJ; Song, E-K; Chee, CE; Chao, Y; Kim, S; Lockhart, AC; Knutson, KL; Yen, J; Franovic, A; Nordstrom, JL; Li, D; Wigginton, J; Davidson-Moncada, JK; Rosales, MK; Bang, Y-J; CP-MGAH22-5 Study Group,
MLA Citation
Catenacci, Daniel V. T., et al. “Margetuximab plus pembrolizumab in patients with previously treated, HER2-positive gastro-oesophageal adenocarcinoma (CP-MGAH22-05): a single-arm, phase 1b-2 trial.Lancet Oncol, vol. 21, no. 8, Aug. 2020, pp. 1066–76. Pubmed, doi:10.1016/S1470-2045(20)30326-0.
URI
https://scholars.duke.edu/individual/pub1451020
PMID
32653053
Source
pubmed
Published In
Lancet Oncol
Volume
21
Published Date
Start Page
1066
End Page
1076
DOI
10.1016/S1470-2045(20)30326-0

Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors.

<jats:p> 490 </jats:p><jats:p> Background: Everolimus (E), an oral rapamycin analogue, is a potent mTOR inhibitor. Combined inhibition of VEGF and mTOR pathways may increase anti-angiogenic and anti-tumor activity. We evaluated E in combination with capecitabine (C), oxaliplatin (O), and bevacizumab (B) in a phase I dose escalation study. </jats:p><jats:p> Methods: Eligible patients (pts) had advanced solid tumors, adequate organ function and no increased risk for class-related toxicities. B and O were given intravenously; C and E were orally administered. Cycle length was 21 days. Doses for level 1: C 850 mg/m<jats:sup>2</jats:sup><jats:sup> </jats:sup>on days 1-14; O 130 mg/m<jats:sup>2 </jats:sup>on day one; B 7.5 mg/kg on day one; and E 5 mg three times a week. Doses for level -1: C 680 mg/m<jats:sup>2</jats:sup>, O100mg/m<jats:sup>2</jats:sup>. An intermediate dose level (-1b) of E escalated to 5 mg five times weekly was added to maximize dose intensity. Dose limiting toxicity (DLT) was assessed in cycle 1. Concomitant administration of CYP3A4 substrates, inhibitors or inducers was prohibited. </jats:p><jats:p> Results: Dose escalation is complete with 27 pts evaluable for toxicity and 24 evaluable for efficacy. Two DLTs (grade 2 intolerable fatigue, anorexia, vomiting and grade 3 diarrhea) were observed in 6 pts in cohort 1. No DLTs were observed in cohort -1; one DLT (rectovaginal fistula) was observed in the -1b cohort. Possible grade ≥3 treatment-related adverse events any time on study (n=1 except as indicated) included diarrhea (n=2), intestinal perforation/fistula, rectovaginal fistula, hypertriglyceridemia (n=3), hyperglycemia, hypoalbuminemia, hyponatremia, peripheral neuropathy, neutropenia (n=2), lymphopenia, thrombocytopenia, hypertension (n=3), deep vein thrombosis, and arterial thrombosis. Adverse events were consistent with known class-related toxicities. For efficacy, 10 pts had a partial response (PR); 10 had stable disease as best response. Of 13 pts with chemorefractory metastatic colorectal cancer (mCRC), 5 had a PR. Of 8 pts with chemonaive mCRC, 5 had a PR. </jats:p><jats:p> Conclusions: E in combination with full dose C, O and B was associated with unacceptable toxicity, primarily GI toxicity. E at 5mg five times weekly, C at 680 mg/m<jats:sup>2</jats:sup><jats:sup> </jats:sup>on days 1-14, O at 100 mg/m<jats:sup>2</jats:sup> and B at 7.5 mg/kg on day one appears well tolerated. Activity was noted in chemorefractory and chemonaive mCRC patients. </jats:p>
Authors
Rangwala, FA; Bendell, JC; Kozloff, M; Arrowood, C; Meadows, J; Tourt-Uhlig, SE; Murphy, J; Meadows, K; Morse, M; Uronis, HE; Hsu, SD; Zafar, Y; Hurwitz, H
MLA Citation
Rangwala, Fatima A., et al. “Phase I study of capecitabine, oxaliplatin, bevacizumab, and everolimus in advanced solid tumors.Journal of Clinical Oncology, vol. 30, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2012, pp. 490–490. Crossref, doi:10.1200/jco.2012.30.4_suppl.490.
URI
https://scholars.duke.edu/individual/pub1406910
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
30
Published Date
Start Page
490
End Page
490
DOI
10.1200/jco.2012.30.4_suppl.490

A phase II study of axalimogene filolisbac for patients with previously treated, unresectable, persistent/recurrent loco-regional or metastatic anal cancer.

Squamous cell carcinoma of the anorectal canal (SCCA) is a rare HPV-related malignancy that is steadily increasing in incidence. A high unmet need exists for patients with persistent loco-regional and metastatic disease. Axalimogene filolisbac (ADXS11-001) is an investigational immunotherapy that stimulates tumor-specific responses against HPV-associated cancers, and has demonstrated benefit in metastatic cervical cancer. We conducted this single-arm, multicenter, phase 2 trial in patients with persistent/recurrent, loco-regional or metastatic SCCA. Patients received ADXS11-001, 1 × 109 colony-forming units intravenously every 3 weeks. A Simon 2-stage design was used to test primary co-endpoints of overall response rate (ORR) and 6-month progression-free survival (PFS) rate. Study would proceed to full enrollment if ORR ≥ 10% or 6-month PFS rate ≥ 20%. Thirty-six patients were treated; 29 patients were evaluable for response. One patient had a prolonged partial response (3.4% ORR). The 6-month PFS rate was 15.5%. Grade 3 adverse event were noted in 10 patients, with the majority being cytokine-release symptoms; one grade 4 adverse event was noted. No grade 5 adverse events occurred. ADXS11-001 was safe and well-tolerated in patients with SCCA. However, this study did not meet either primary endpoint. ADXS11-001 may be more beneficial when administered in combination with other cytotoxic or targeted agents.
Authors
Eng, C; Fakih, M; Amin, M; Morris, V; Hochster, HS; Boland, PM; Uronis, H
MLA Citation
Eng, Cathy, et al. “A phase II study of axalimogene filolisbac for patients with previously treated, unresectable, persistent/recurrent loco-regional or metastatic anal cancer.Oncotarget, vol. 11, no. 15, Apr. 2020, pp. 1334–43. Epmc, doi:10.18632/oncotarget.27536.
URI
https://scholars.duke.edu/individual/pub1447321
PMID
32341753
Source
epmc
Published In
Oncotarget
Volume
11
Published Date
Start Page
1334
End Page
1343
DOI
10.18632/oncotarget.27536

Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC).

<jats:p> 65 </jats:p><jats:p> Background: Trastuzumab (T) + chemo is standard first-line therapy (tx) for HER2+ gastroesophageal adenocarcinoma (GEA) pts, though progression ensues in 6-8 months. The approved second-line tx is ramucirumab +/- paclitaxel (R+PAC). Pts with GC are less responsive to R+PAC than gastroesophageal junction (GEJ) pts, in particular HER2+ GC, and no anti-HER2 agents are approved in post-T setting. We report results of combination M+P in HER2+ GC pts and describe a biological rationale for this population. M is an anti-HER2 mAb Fc optimized for enhanced binding to activating FcgRIIIa (CD16A) and decreased binding to inhibitory FcgRIIb (CD32B). M demonstrated an enhanced Fc-dependent MoA, including enhanced ADCC. Methods: HER2+, PD-L1-unselected, second-line GEA pts post T progression received M (15 mg/kg) + P (200 mg) Q3wk. Safety, objective response rate (ORR), median overall &amp; progression-free survival (mOS, mPFS), disease control rate (DCR), circulating tumor DNA, &amp; tumor PD-L1 expression were assessed. Results: To date, 66 GEA pts were dosed; 35 (53%) GC and 31 (47%) GEJ. Overall, 12/66 (18.2%) had tx-related adverse events ≥ grade 3; 5 had drug-related SAEs: dehydration, diabetic ketoacidosis, hypotension and pneumonitis, each a single event, and 2 events of autoimmune hepatitis. Eligibility was based on archival HER2 expression; an exploratory endpoint measured retention of HER2 expression post-T by ERBB2 ctDNA. HER2 expression was lost in 23/56 (41.1%) of pts tested post T. HER2 retention was higher in pts with GC versus GEJ (65.8% vs. 44.8%) and in GEA pts with IHC 3+ vs 2+ archival tumors (61.7% vs 47.4%, respectively). Furthermore, GC had higher PD-L1 expression than GEJ, 53.3 vs. 33.3%, respectively. This coincided with more responses in IHC3+ GC pts, ORR 12/29 (41.4%; 95% CI 23.5-61.1), DCR 21/29 (72.4%; 95% CI 52.8-87.3), mPFS 5.5 months (95% CI 2.3-7.6), mOS not reached, with lower bound of 9.1 months for 95% CI. Enrollment of an additional 25 pts enriched for IHC3+ GC is ongoing. Conclusions: Results suggest that M+P, a chemo-free regimen, demonstrates acceptable tolerability and has encouraging preliminary activity in second-line HER2+ GEA, specifically in GC pts who retain ERBB2 amp prior to second-line tx. Clinical trial information: NCT02689284. </jats:p>
Authors
Catenacci, DVT; Lim, KH; Uronis, HE; Kang, Y-K; Ng, MCH; Gold, PJ; Enzinger, PC; Lee, KW; Lacy, J; Park, SH; Yen, J; Odegaard, J; Franovic, A; Baughman, JE; Wynter-Horton, A; Chen, F; Moore, PA; Wu, T; Davidson-Moncada, JK; Bang, Y-J
MLA Citation
Catenacci, Daniel V. T., et al. “Antitumor activity of margetuximab (M) plus pembrolizumab (P) in patients (pts) with advanced HER2+ (IHC3+) gastric carcinoma (GC).Journal of Clinical Oncology, vol. 37, no. 4_suppl, American Society of Clinical Oncology (ASCO), 2019, pp. 65–65. Crossref, doi:10.1200/jco.2019.37.4_suppl.65.
URI
https://scholars.duke.edu/individual/pub1416511
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
37
Published Date
Start Page
65
End Page
65
DOI
10.1200/jco.2019.37.4_suppl.65

Safety at the Time of the COVID-19 Pandemic: How to Keep our Oncology Patients and Healthcare Workers Safe.

The novel coronavirus, SARS-CoV-2, was first detected as a respiratory illness in December 2019 in Wuhan City, China. Since then, coronavirus disease 2019 (COVID-19) has impacted every aspect of our lives worldwide. In a time when terms such as social distancing and flattening the curve have become a part of our vernacular, it is essential that we understand what measures can be implemented to protect our patients and healthcare workers. Undoubtedly, healthcare providers have had to rapidly alter care delivery models while simultaneously acknowledging the crucial unknowns of how these changes may affect clinical outcomes. This special feature reviews strategies on how to mitigate transmission of COVID-19 in an effort to reduce morbidity and mortality associated with the disease for patients with cancer without infection, for patients with cancer with COVID-19 infection, and for the healthcare workers caring for them, while continuing to provide the best possible cancer care. [Editor's Note: This article includes the most current information available at time of publication; however, recommendations regarding public safety and practice may change rapidly in this situation. Individuals should get the most up to date information from the CDC website.].
Authors
Cinar, P; Kubal, T; Freifeld, A; Mishra, A; Shulman, L; Bachman, J; Fonseca, R; Uronis, H; Klemanski, D; Slusser, K; Lunning, M; Liu, C
MLA Citation
Cinar, Pelin, et al. “Safety at the Time of the COVID-19 Pandemic: How to Keep our Oncology Patients and Healthcare Workers Safe.Journal of the National Comprehensive Cancer Network : Jnccn, Apr. 2020, pp. 1–6. Epmc, doi:10.6004/jnccn.2020.7572.
URI
https://scholars.duke.edu/individual/pub1438557
PMID
32294617
Source
epmc
Published In
Jnccn Journal of the National Comprehensive Cancer Network
Published Date
Start Page
1
End Page
6
DOI
10.6004/jnccn.2020.7572

Research Areas:

Adenocarcinoma
Administration, Oral
Adult
Aged
Aged, 80 and over
Ampulla of Vater
Anastomotic Leak
Angiogenesis Inhibitors
Aniline Compounds
Anoxia
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Combined Chemotherapy Protocols
Anus Neoplasms
Anxiety
Bevacizumab
Carcinoma, Squamous Cell
Chemoradiotherapy
Chemoradiotherapy, Adjuvant
Colorectal Neoplasms
Combined Modality Therapy
Common Bile Duct Neoplasms
Depression
Esophagectomy
Female
Follow-Up Studies
Gastrointestinal Neoplasms
Humans
Hydroxamic Acids
Hypocalcemia
Hypokalemia
Hypoxia
Immunosuppressive Agents
Injections, Intravenous
Kaplan-Meier Estimate
Language
Leukocytes, Mononuclear
Liver Neoplasms
Lymph Nodes
Lymphatic Irradiation
Male
Middle Aged
Models, Statistical
Neoadjuvant Therapy
Neoplasm Recurrence, Local
Organoplatinum Compounds
Oxaliplatin
Pain Measurement
Palliative Care
Pancreatic Neoplasms
Patient Satisfaction
Photons
Platinum Compounds
Protein Kinase Inhibitors
Psychometrics
Pyrimidines
Quality of Life
Randomized Controlled Trials as Topic
Regression Analysis
Reproducibility of Results
Retrospective Studies
Risk Factors
Sirolimus
Socioeconomic Factors
Sulfonamides
Survival Rate
Thiazoles
Tumor Markers, Biological
Young Adult