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:

KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.

<jats:p> 228 </jats:p><jats:p> Background: Gastric and esophageal adenocarcinomas are a leading cause of cancer death worldwide. Many of these patients (pts) present with locally advanced unresectable or metastatic disease and are treated with combination cytotoxic chemotherapy. Single agent P is FDA approved for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma (GEJ) whose tumors have a combined positive score (CPS) ≥ 1 after disease progression on or after two lines of therapy including fluoropyrimidine and platinum and her2/neu-targeted therapy (if indicated). More effective therapy is needed earlier in the disease trajectory. We conducted a single-arm phase II trial to establish the safety and efficacy of first-line C and O + P. Methods: Pts with previously untreated metastatic GE adenocarcinoma regardless of PDL-1 status received intravenous (IV) P 200mg with IV O 130mg/m<jats:sup>2</jats:sup> every three weeks and oral C 850mg/m<jats:sup>2</jats:sup> twice daily for 14 days on/7 days off. After the 6 patient safety cohort, pts first completed a biomarker cycle that included fresh tumor biopsy before P and one week after P before chemotherapy started. Archived FFPE tumor samples were also obtained from all pts with available tissue. The primary endpoint was progression free survival (PFS); secondary endpoints included response rate (RR) and overall survival (OS). Results: 36 pts were enrolled and 34 pts were evaluable for efficacy (1 pt withdrew for personal reasons before end of cycle 1 and 1 pt had immune-related toxicity during cycle 1 and was taken off study before any efficacy assessment). 9 pts (26%) had an esophageal primary, 18 pts (53%) had a GEJ primary and 7 pts (21%) had a gastric primary. Median PFS was 7.6 months [95% CI: 5.8 to 12.2], RR was 72.7% [95% CI: 57% to 88%], and median OS was 15.8 months [95% CI: 11.6 to NE]. 27 patients (81.8%) had decrease in disease burden (ranging from -19% to -100%). After &gt; 18 months of follow-up, 5 patients remained in durable complete response (CR). Immune-mediated treatment related adverse events (TRAEs) included thyroid disorders (n=5; 14%), colitis (n=4; 11%), adrenal insufficiency (n=2; 5%), and type 1 diabetes (n=1). Sixteen patients (44%) experienced grade 3 or 4 TRAEs. There were no grade 5 TRAEs. Conclusions: The combination of C and O + P had acceptable safety and significant clinical activity. These promising results indicate that C and O + P merits further study as a first line option for patients with unresectable locally advanced or metastatic GE adenocarcinoma. Updated survival and correlative data will be presented. Clinical trial information: NCT03342937. </jats:p>
Authors
Uronis, HE; Rushing, C; Blobe, GC; Hsu, SD; Mettu, NB; Wells, JL; Niedzwiecki, D; Hartman, L; Moyer, A; Hurwitz, HI; Strickler, JH
MLA Citation
Uronis, Hope Elizabeth, et al. “KEYlargo: A phase II study of first-line pembrolizumab (P), capecitabine (C), and oxaliplatin (O) in HER2-negative gastroesophageal (GE) adenocarcinoma.Journal of Clinical Oncology, vol. 39, no. 3_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 228–228. Crossref, doi:10.1200/jco.2021.39.3_suppl.228.
URI
https://scholars.duke.edu/individual/pub1478769
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
228
End Page
228
DOI
10.1200/jco.2021.39.3_suppl.228

Phase Ib/II study of pembrolizumab with lanreotide depot for advanced, progressive gastroenteropancreatic neuroendocrine tumors (PLANET).

<jats:p> 369 </jats:p><jats:p> Background: Pembrolizumab has antitumor activity in a subset of GEP-NETs patients. We hypothesized that the lanreotide, by its antitumor effects and reduction of serotonin, a modulator of immunity, would synergize with pembrolizumab in low/intermediate grade GEPNETs. Methods: GEP-NETs patients who had progressed on a prior somatostatin analogue received lanreotide 90mg sq and pembrolizumab 200mg IV every 3 weeks until progressive disease or intolerable toxicity. The primary endpoint was ORR at any time on study and secondary endpoints were PFS and OS. Results: 22 patients were treated (F/M 10/12; Caucasian/AA/other 10/7/5; GI/pancreatic 14/8; median Ki67 5%, median time since diagnosis 5.3 yrs (IQR 2.3-7.9 yrs)). Prior octreotide LAR/lanreotide/both was administered to 20/1/1. Patients had a median of 2 prior systemic therapies (range 1-9) and six had prior locoregional therapy and 3 external beam radiotherapy. Of the 12 tumors analyzed thus far, 4 had detectable PD-L1 expression and 11 had detectable TILs. A median of 6 pembrolizumab doses (range 2-15) and 7 lanreotide doses (range 2-15) were administered. Six patients experienced treatment related SAEs (abdominal pain, pneumonitis, colitis, and hyperglycemia, all related to the pembrolizumab). Selected treatment related adverse events included: Hypothyroidism 23%, colitis 9%, hyperglycemia 14%, and pneumonitis 5%. Best response by RECIST 1.1 was SD/PD/Not available:39/52/9% and by irRECIST was 43/48/9%. Median PFS was 5.4 months (95% CI 1.7-8.3 mo). The median overall survival at a median follow-up of 15 months was not reached. Peripheral blood immunologic correlates will be reported subsequently. Conclusions: In a population of GEP-NET patients, progressing on a median of 2 prior therapies, including prior somatostatin analogue therapy, a minority of whom had PD-L1 expressing tumors, the combination of lanreotide and pembrolizumab produced stable disease in approximately 40% of patients. No new safety signals were identified. Clinical trial information: NCT03043664. </jats:p>
Authors
Morse, M; Halperin, DM; Uronis, HE; Hsu, DS; Hurwitz, H; Bolch, E; Warren, D; Haley, S; John, L; Moyer, A; Rushing, CN; Niedzwiecki, D
MLA Citation
Morse, Michael, et al. “Phase Ib/II study of pembrolizumab with lanreotide depot for advanced, progressive gastroenteropancreatic neuroendocrine tumors (PLANET).Journal of Clinical Oncology, vol. 39, no. 3_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. 369–369. Crossref, doi:10.1200/jco.2021.39.3_suppl.369.
URI
https://scholars.duke.edu/individual/pub1480555
Source
crossref
Published In
Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Volume
39
Published Date
Start Page
369
End Page
369
DOI
10.1200/jco.2021.39.3_suppl.369

Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.

BACKGROUND: No adjuvant treatment has been established for patients who remain at high risk for recurrence after neoadjuvant chemoradiotherapy and surgery for esophageal or gastroesophageal junction cancer. METHODS: We conducted CheckMate 577, a global, randomized, double-blind, placebo-controlled phase 3 trial to evaluate a checkpoint inhibitor as adjuvant therapy in patients with esophageal or gastroesophageal junction cancer. Adults with resected (R0) stage II or III esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy and had residual pathological disease were randomly assigned in a 2:1 ratio to receive nivolumab (at a dose of 240 mg every 2 weeks for 16 weeks, followed by nivolumab at a dose of 480 mg every 4 weeks) or matching placebo. The maximum duration of the trial intervention period was 1 year. The primary end point was disease-free survival. RESULTS: The median follow-up was 24.4 months. Among the 532 patients who received nivolumab, the median disease-free survival was 22.4 months (95% confidence interval [CI], 16.6 to 34.0), as compared with 11.0 months (95% CI, 8.3 to 14.3) among the 262 patients who received placebo (hazard ratio for disease recurrence or death, 0.69; 96.4% CI, 0.56 to 0.86; P<0.001). Disease-free survival favored nivolumab across multiple prespecified subgroups. Grade 3 or 4 adverse events that were considered by the investigators to be related to the active drug or placebo occurred in 71 of 532 patients (13%) in the nivolumab group and 15 of 260 patients (6%) in the placebo group. The trial regimen was discontinued because of adverse events related to the active drug or placebo in 9% of the patients in the nivolumab group and 3% of those in the placebo group. CONCLUSIONS: Among patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, disease-free survival was significantly longer among those who received nivolumab adjuvant therapy than among those who received placebo. (Funded by Bristol Myers Squibb and Ono Pharmaceutical; CheckMate 577 ClinicalTrials.gov number, NCT02743494.).
Authors
Kelly, RJ; Ajani, JA; Kuzdzal, J; Zander, T; Van Cutsem, E; Piessen, G; Mendez, G; Feliciano, J; Motoyama, S; Lièvre, A; Uronis, H; Elimova, E; Grootscholten, C; Geboes, K; Zafar, S; Snow, S; Ko, AH; Feeney, K; Schenker, M; Kocon, P; Zhang, J; Zhu, L; Lei, M; Singh, P; Kondo, K; Cleary, JM; Moehler, M; CheckMate 577 Investigators,
MLA Citation
Kelly, Ronan J., et al. “Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer.N Engl J Med, vol. 384, no. 13, Apr. 2021, pp. 1191–203. Pubmed, doi:10.1056/NEJMoa2032125.
URI
https://scholars.duke.edu/individual/pub1477691
PMID
33789008
Source
pubmed
Published In
The New England Journal of Medicine
Volume
384
Published Date
Start Page
1191
End Page
1203
DOI
10.1056/NEJMoa2032125

Feasibility, engagement, and acceptability of a behavioral pain management intervention for colorectal cancer survivors with pain and psychological distress: data from a pilot randomized controlled trial.

PURPOSE: Colorectal cancer survivors report pain and psychological distress to be burdensome long-term cancer consequences. Quality cancer survivorship care includes interventions for managing these symptoms. Yet, no studies have tested the efficacy of an accessible behavioral intervention for colorectal cancer survivors with pain and comorbid psychological distress. This paper reports on the feasibility (i.e., accrual, attrition, and adherence to study procedures), engagement, acceptability, and descriptive outcomes of a telephone-based coping skills training (CST) intervention. METHODS: This randomized pilot trial assigned colorectal cancer patients (N=31) to 5 sessions of CST or standard care. CST sessions focused on cognitive-behavioral theory-based coping skills tailored to colorectal cancer symptoms of pain and psychological distress. Participants completed assessments of pain severity, self-efficacy for pain management, health-related quality of life, and psychological distress at baseline, post-treatment, and 3-month follow-up. RESULTS: Data indicated strong feasibility, evidenced by high completion rates for intervention sessions and assessments (93% completed all sessions; M=48.7 days; baseline=100%; post-treatment=97%; 3-month follow-up=94%). Participants demonstrated robust engagement with CST (M days per week with reported skills use=3.8) and reported high protocol satisfaction (M=3.6/4.0). Descriptive statistics showed self-efficacy for pain management and health-related quality of life improved for all participants. CONCLUSION: Findings suggest that a telephone-based CST intervention has strong feasibility, evidenced by accrual, low attrition, and adherence to intervention sessions and assessments. Likewise, participant engagement and acceptability with CST were high. These data provide a foundation for larger randomized efficacy trials of the telephone-based CST intervention.
Authors
URI
https://scholars.duke.edu/individual/pub1475456
PMID
33686520
Source
pubmed
Published In
Support Care Cancer
Published Date
DOI
10.1007/s00520-021-06126-8

Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer.

TRIAL INFORMATION: ClinicalTrials.gov Identifier: NCT02008383 Sponsor: Duke University Principal Investigator: John H. Strickler IRB Approved: Yes LESSONS LEARNED: Antitumor activity was observed in the study population. Dose modifications of cabozantinib improve long-term tolerability. Biomarkers are needed to identify patient populations most likely to benefit. Further study of cabozantinib with or without panitumumab in patients with metastatic colorectal cancer is warranted. BACKGROUND: The epidermal growth factor receptor (EGFR) antibody panitumumab is active in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC), but nearly all patients experience resistance. MET amplification is a driver of panitumumab resistance. Cabozantinib is an inhibitor of multiple kinases, including vascular endothelial growth factor receptor 2 (VEGFR2) and c-MET, and may delay or reverse anti-EGFR resistance. METHODS: In this phase Ib clinical trial, we established the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of cabozantinib and panitumumab. We then treated an expansion cohort to further describe the tolerability and clinical activity of the RP2D. Eligibility included patients with KRAS WT mCRC (later amended to include only RAS WT mCRC) who had received prior treatment with a fluoropyrimidine, oxaliplatin, irinotecan, and bevacizumab. RESULTS: Twenty-five patients were enrolled and treated. The MTD/RP2D was cabozantinib 60 mg p.o. daily and panitumumab 6 mg/kg I.V. every 2 weeks. The objective response rate (ORR) was 16%. Median progression free survival (PFS) was 3.7 months (90% confidence interval [CI], 2.3-7.1). Median overall survival (OS) was 12.1 months (90% CI, 7.5-14.3). Five patients (20%) discontinued treatment due to toxicity, and 18 patients (72%) required a dose reduction of cabozantinib. CONCLUSION: The combination of cabozantinib and panitumumab has activity. Dose reductions of cabozantinib improve tolerability.
Authors
Strickler, JH; Rushing, CN; Uronis, HE; Morse, MA; Niedzwiecki, D; Blobe, GC; Moyer, AN; Bolch, E; Webb, R; Haley, S; Hatch, AJ; Altomare, IP; Sherrill, GB; Chang, DZ; Wells, JL; Hsu, SD; Jia, J; Zafar, SY; Nixon, AB; Hurwitz, HI
MLA Citation
Strickler, John H., et al. “Cabozantinib and Panitumumab for RAS Wild-Type Metastatic Colorectal Cancer.Oncologist, Jan. 2021. Pubmed, doi:10.1002/onco.13678.
URI
https://scholars.duke.edu/individual/pub1472247
PMID
33469991
Source
pubmed
Published In
Oncologist
Published Date
DOI
10.1002/onco.13678

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