Michael Morse

Overview:

We are studying the use of immune therapies to treat various cancers, including gastrointestinal, breast, and lung cancers and melanoma. These therapies include vaccines based on dendritic cells developed in our laboratory as well as vaccines based on peptides, viral vectors, and DNA plasmids. Our group is also a national leader in the development and use of laboratory assays for demonstrating immunologic responses to cancer vaccines. Finally, we are developing immunotherapies based on adoptive transfer of tumor and viral antigen-specific T cells.

Our current clinical trials include phase I and II studies of immunotherapy for: patients with metastatic malignancies expressing CEA, pancreatic cancer, colorectal cancer, breast cancer, and ovarian cancer, and leukemias following HSCT. My clinical area of expertise is in gastrointestinal oncology, in particular, the treatment of hepatic malignancies, and malignant melanoma.

Key words: dendritic cells, immunotherapy, vaccines, T cells, gastrointestinal oncology, melanoma, hepatoma

Positions:

Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Professor in the Department of Surgery

Surgery, Surgical Sciences
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1990

Yale University

Medical Resident, Medicine

University of Washington

Fellow in Hematology-Oncology, Medicine

Duke University

Grants:

A Phase 1 multicenter, open label study of enadenotucirev combined with PD-1 inhibitor in subjects with metastatic or advanced epithelial tumors

Administered By
Duke Cancer Institute
Awarded By
PsiOxus Therapeutics Ltd.
Role
Principal Investigator
Start Date
End Date

A Randomized, Open-label, Multi-center Phase III Study of Durvalumab and Tremelimumab as First-line Treatment in Patients with Unresectable Hepatocellular Carcinoma (HIMALAYA)

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

A Phase 1b, Randomized, Open-Label Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) in Combination With Cisplatin Plus Gemcitabine and PEGPH20 in Combination With Atezolizumab and Cisplatin Plus Gemcitabine Compared With Cisplatin Plus Ge

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

An Open-Label Multicenter Phase 1 Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of H3B-6527 in Subjects With Advanced Hepatocellular Carcinoma or Intrahepatic Cholangiocarcinoma

Administered By
Duke Cancer Institute
Awarded By
H3 Biomedicine, Inc.
Role
Principal Investigator
Start Date
End Date

A MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF VARLITINIB PLUS CAPECITABINE VERSUS PLACEBO PLUS CAPECITABINE IN PATIENTS WITH ADVANCED OR METASTATIC BILIARY TRACT CANCER AS SECOND-LINE SYSTEMIC THERAPY

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

Publications:

Atrial fibrillation ablation using a closed irrigation radiofrequency ablation catheter.

BACKGROUND: Catheter ablation is an effective therapy for symptomatic, medically refractory atrial fibrillation (AF). Open-irrigated radiofrequency (RF) ablation catheters produce transmural lesions at the cost of increased fluid delivery. In vivo models suggest closed-irrigated RF catheters create equivalent lesions, but clinical outcomes are limited. METHODS: A cohort of 195 sequential patients with symptomatic AF underwent stepwise AF ablation (AFA) using a closed-irrigation ablation catheter. Recurrence of AF was monitored and outcomes were evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: Mean age was 59.0 years, 74.9% were male, 56.4% of patients were paroxysmal and mean duration of AF was 5.4 years. Patients had multiple comorbidities including hypertension (76.4%), tobacco abuse (42.1%), diabetes (17.4%), and obesity (mean body mass index 30.8). The median follow-up was 55.8 weeks. Overall event-free survival was 73.6% with one ablation and 77.4% after reablation (reablation rate was 8.7%). Median time to recurrence was 26.9 weeks. AF was more likely to recur in patients being treated with antiarrhythmic therapy at the time of last follow-up (recurrence rate 30.3% with antiarrhythmic drugs, 13.2% without antiarrhythmic drugs; hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.1-4.4, P = 0.024) and in those with a history of AF greater than 2 years duration (HR 2.7, 95% CI 1.1-6.9, P = 0.038). CONCLUSIONS: Our study represents the largest cohort of patients receiving AFA with closed-irrigation ablation catheters. We demonstrate comparable outcomes to those previously reported in studies of open-irrigation ablation catheters. Given the theoretical benefits of a closed-irrigation system, a large head-to-head comparison using this catheter is warranted.
Authors
Golden, K; Mounsey, JP; Chung, E; Roomiani, P; Morse, MA; Patel, A; Gehi, A
MLA Citation
Golden, Keith, et al. “Atrial fibrillation ablation using a closed irrigation radiofrequency ablation catheter.Pacing Clin Electrophysiol, vol. 35, no. 5, May 2012, pp. 506–16. Pubmed, doi:10.1111/j.1540-8159.2011.03309.x.
URI
https://scholars.duke.edu/individual/pub1451440
PMID
22296283
Source
pubmed
Published In
Pacing Clin Electrophysiol
Volume
35
Published Date
Start Page
506
End Page
516
DOI
10.1111/j.1540-8159.2011.03309.x

Antiproliferative effects of telotristat ethyl in patients with neuroendocrine tumors: The teleace real-world chart review study

© 2020 Morse et al. Purpose: Neuroendocrine tumors (NETs) associated with carcinoid syndrome (CS) over-produce serotonin, mediated by tryptophan hydroxylase-1 (TPH1). The TPH inhibitor telo-tristat ethyl (TE) reduces peripheral serotonin and relieves CS symptoms. We conducted a real-world clinical practice study to explore the effects of TE on tumor growth in patients with NETs and CS. Patients and Methods: Single-arm, pre/post chart review study of patients with advanced NETs who received TE for ≥6 months and had ≥2 radiological scans within 12 months before and ≥1 scan after TE initiation. Linear regression and longitudinal analyses assessed changes in tumor size controlling for background NET treatment. Results: Two hundred patients were enrolled, most (61%) had well-differentiated gastrointestinal NETs (61%) and received TE for an average of 12 months (SD, 7.3). Mean reduction in tumor size after TE initiation was 0.59 cm (p=0.006). Longitudinal analysis showed an 8.5% reduction in tumor size (p=0.045) from pre-to post-TE periods. Documented NET treatment prior to initiating TE and time between scans were not significant predictors of changes in tumor size. Results were consistent in a subgroup of patients with the same documented NET treatment before and after initiating TE. Conclusion: TE may have antitumor effects consistent with serotonin overproduction in tumor growth.
Authors
Morse, MA; Liu, E; Joish, VN; Huynh, L; Cheng, M; Duh, MS; Seth, K; Lapuerta, P; Metz, DC
MLA Citation
Morse, M. A., et al. “Antiproliferative effects of telotristat ethyl in patients with neuroendocrine tumors: The teleace real-world chart review study.” Cancer Management and Research, vol. 12, Jan. 2020, pp. 6607–14. Scopus, doi:10.2147/CMAR.S261257.
URI
https://scholars.duke.edu/individual/pub1454481
Source
scopus
Published In
Cancer Management and Research
Volume
12
Published Date
Start Page
6607
End Page
6614
DOI
10.2147/CMAR.S261257

Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study.

PURPOSE:To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. METHODS:In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. RESULTS:Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. CONCLUSIONS:177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11.
Authors
Strosberg, J; Kunz, PL; Hendifar, A; Yao, J; Bushnell, D; Kulke, MH; Baum, RP; Caplin, M; Ruszniewski, P; Delpassand, E; Hobday, T; Verslype, C; Benson, A; Srirajaskanthan, R; Pavel, M; Mora, J; Berlin, J; Grande, E; Reed, N; Seregni, E; Paganelli, G; Severi, S; Morse, M; Metz, DC; Ansquer, C; Courbon, F; Al-Nahhas, A; Baudin, E; Giammarile, F; Taïeb, D; Mittra, E; Wolin, E; O'Dorisio, TM; Lebtahi, R; Deroose, CM; Grana, CM; Bodei, L; Öberg, K; Polack, BD; He, B; Mariani, MF; Gericke, G; Santoro, P; Erion, JL; Ravasi, L; Krenning, E; NETTER-1 study group,
MLA Citation
Strosberg, Jonathan, et al. “Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study.European Journal of Nuclear Medicine and Molecular Imaging, vol. 47, no. 10, Sept. 2020, pp. 2372–82. Epmc, doi:10.1007/s00259-020-04709-x.
URI
https://scholars.duke.edu/individual/pub1446592
PMID
32123969
Source
epmc
Published In
European Journal of Nuclear Medicine and Molecular Imaging
Volume
47
Published Date
Start Page
2372
End Page
2382
DOI
10.1007/s00259-020-04709-x

Optimizing the use of thrombolytics in ST-segment elevation myocardial infarction.

The advent of thrombolytic therapy was a major advance in the treatment of ST-segment elevation myocardial infarction (STEMI). The administration of fibrinolytic reperfusion therapy can reduce mortality rates by as much as 30%, with the greatest benefit observed if therapy is administered soon after symptom onset. Outcomes with thrombolytic therapy are improved if there is adjunctive treatment with aspirin, clopidogrel and an anti-thrombin agent. Although there is evidence that primary percutaneous coronary intervention (PCI) is the most effective reperfusion strategy, the majority of hospitals still do not have PCI capabilities and, thus, thrombolytic therapy remains a cornerstone of treatment for STEMI. Trials of thrombolytic therapy have demonstrated that initial patency rates can approach 85%, but there is still a need for improvement of non-invasive markers that predict failure or re-occlusion of the infarct-related artery. Because of the overwhelming data demonstrating the importance of rapid reperfusion, current studies are examining the role of earlier treatment of patients with STEMI via pre-hospital administration and/or coordinated systems for rapid diagnosis, transfer and delivery of definitive care. Facilitated PCI, a strategy of thrombolytic therapy followed by immediate PCI, has not been shown to be beneficial and current studies are examining the optimal timing of coronary angiography after thrombolytic therapy.
Authors
Morse, MA; Todd, JW; Stouffer, GA
MLA Citation
Morse, Michael A., et al. “Optimizing the use of thrombolytics in ST-segment elevation myocardial infarction.Drugs, vol. 69, no. 14, Oct. 2009, pp. 1945–66. Pubmed, doi:10.2165/11317670-000000000-00000.
URI
https://scholars.duke.edu/individual/pub1451441
PMID
19747010
Source
pubmed
Published In
Drugs
Volume
69
Published Date
Start Page
1945
End Page
1966
DOI
10.2165/11317670-000000000-00000

Phase II Study of Ensituximab, a Novel Chimeric Monoclonal Antibody, in Adults with Unresectable, Metastatic Colorectal Cancer.

PURPOSE: Patients with metastatic colorectal cancer refractory to chemotherapy have limited treatment options. Ensituximab (NEO-102) is a novel chimeric mAb targeting a variant of MUC5AC with specificity to colorectal cancer. PATIENTS AND METHODS: Single-arm, phase II trial assessed the efficacy and safety of ensituximab in patients with advanced, refractory cancer who expressed MUC5AC antigen in tumor tissue. Ensituximab was administered intravenously every 2 weeks with 3 mg/kg as recommended phase II dose (RP2D). A minimum sample size of 43 patients was required on the basis of the assumption that ensituximab would improve median overall survival (OS) by 7 months using a one-sided significance level of 10% and 80% power. Written informed consent was obtained from all patients. RESULTS: Sixty-three patients with advanced, refractory colorectal cancer were enrolled and 53 subjects were treated in phase II arm. Median age was 58 years and 46% of the patients were female. Among 57 evaluable patients, median OS was 6.8 months. No responses were observed, and stable disease was achieved in 21% of the patients. The most common treatment-related adverse events (AE) at RP2D included fatigue (38%), anemia (30%), nausea (15%), vomiting (11%), increased bilirubin (9%), constipation (8%), decreased appetite (6%), and diarrhea (6%). Serious AEs at least possibly related to ensituximab occurred in 4 patients and included anemia, nausea, increased bilirubin, and hypoxia. No patients discontinued treatment due to drug-related AEs. CONCLUSIONS: Ensituximab was well tolerated and demonstrated modest antitumor activity in patients with heavily pretreated refractory colorectal cancer.
Authors
Kim, RD; Azad, NS; Morse, MA; Poplin, E; Mahipal, A; Tan, B; Mavroukakis, SA; Fantini, M; Tsang, KY; Zaki, A; Torrealba, J; Arlen, PM; Beg, MS
MLA Citation
Kim, Richard D., et al. “Phase II Study of Ensituximab, a Novel Chimeric Monoclonal Antibody, in Adults with Unresectable, Metastatic Colorectal Cancer.Clin Cancer Res, vol. 26, no. 14, July 2020, pp. 3557–64. Pubmed, doi:10.1158/1078-0432.CCR-20-0426.
URI
https://scholars.duke.edu/individual/pub1438301
PMID
32303539
Source
pubmed
Published In
Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Volume
26
Published Date
Start Page
3557
End Page
3564
DOI
10.1158/1078-0432.CCR-20-0426