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:

Clinical efficacy of intra-cavitary infusions of autologous dendritic cell/cytokine-induced killer cell products for the treatment of refractory malignant pleural effusions and ascites.

To explore the safety and efficacy of intra-cavitary infusions of autologous mixed dendritic cell (DC)-cytokine-induced killer (CIK) cell products in advanced cancer patients with malignant pleural effusions or ascites. DC-CIKs were expanded ex vivo (mean yield of 1.36×109 cells (range, 0.74~4.98×109)) from peripheral blood mononuclear cells obtained by repeated venipuncture or apheresis. Patients received at least 1 cycle of 3 infusions of the DC-CIKs administered by indwelling catheter into the pleural or peritoneal cavity every other day. The volume of malignant effusions was assessed radiologically. Peripheral blood lymphocyte populations were enumerated by flow cytometry. Quality of life (QoL) during the DC-CIK infusions was assessed by the EORTC QLQ-30 instrument. ctDNA sequencing was performed to analyze gene clonal load and molecular tumor burden during the infusion treatment. Thirty-seven patients with breast, lung and other malignancies were enrolled. The results showed that intra-cavitary DC-CIK infusions (16 intrapleural and 21 intraperitoneal) were well-tolerated with no grade 3/4 adverse events. There was one complete response with effusion disappearance (CR) (3%), 13 partial responses (PR) (35%), 12 with stable disease (SD) (32%) and 11 with progressive disease (PD) (30%), resulting in a clinical effusion control rate (CCR) of 70% (26/37). The total number of infused CIKs and the CD3+/CD8+ and CD8+/CD28+ T cell frequencies within the CIKs were associated with effusion control (P=0.013). Moreover, increased peripheral blood CD3+/CD8+ (P=0.035) and decreased CD4+/CD25+ T cell frequencies (P=0.041) following the DC-CIK infusions were associated with malignant effusion and ascites control. Reductions in ctDNA correlated with clinical benefit. In conclusion, intra-cavitary autologous cellular immunotherapy is an alternative method to effectively control malignant pleural effusions and ascites. The overall effusion control rate was associated with higher peripheral blood effector T cell frequencies.
Authors
He, Z; Wang, S; Qiao, G; Wang, X; Zhou, X; Zhu, S; Yuan, Y; Morse, MA; Hobeika, A; Ren, J; Lyerly, HK
URI
https://scholars.duke.edu/individual/pub1454060
PMID
32774747
Source
pubmed
Published In
American Journal of Translational Research
Volume
12
Published Date
Start Page
3940
End Page
3952

Targeting the glucagon receptor signaling pathway as a novel strategy to counteract PI3K inhibitor induced hyperglycemia while sustaining tumor PI3K inhibition.

Authors
Wang, J; Osada, T; Morse, MA; Calzone, F; Yan, H; Thai, D; Lyerly, HK
MLA Citation
URI
https://scholars.duke.edu/individual/pub1474786
PMID
33576297
Source
pubmed
Published In
Leuk Lymphoma
Published Date
Start Page
1
End Page
6
DOI
10.1080/10428194.2021.1881504

Vaccine Therapies for Cancer: Then and Now.

There are strong biologic and preclinical rationales for the development of therapeutic cancer vaccines; however, the clinical translation of this treatment strategy has been challenging. It is now understood that many previous clinical trials of cancer vaccines used target antigens or vaccine designs that inherently lacked sufficient immunogenicity to induce clinical responses. Despite the historical track record, breakthrough advances in cancer immunobiology and vaccine technologies have supported continued interest in therapeutic cancer vaccinations, with the hope that next-generation vaccine strategies will enable patients with cancer to develop long-lasting anti-tumor immunity. There has been substantial progress identifying antigens and vaccine vectors that lead to strong and broad T cell responses, tailoring vaccine designs to achieve optimal antigen presentation, and finding combination partners employing complementary mechanisms of action (e.g., checkpoint inhibitors) to overcome the diverse methods cancer cells use to evade and suppress the immune system. Results from randomized, phase 3 studies testing therapeutic cancer vaccines based on these advances are eagerly awaited. Here, we summarize the successes and failures in the clinical development of cancer vaccines, address how this historical experience and advances in science and technology have shaped efforts to improve vaccines, and offer a clinical perspective on the future role of vaccine therapies for cancer.
Authors
MLA Citation
Morse, Michael A., et al. “Vaccine Therapies for Cancer: Then and Now.Target Oncol, vol. 16, no. 2, Mar. 2021, pp. 121–52. Pubmed, doi:10.1007/s11523-020-00788-w.
URI
https://scholars.duke.edu/individual/pub1473080
PMID
33512679
Source
pubmed
Published In
Target Oncol
Volume
16
Published Date
Start Page
121
End Page
152
DOI
10.1007/s11523-020-00788-w

Survival and Clinical Outcomes with Telotristat Ethyl in Patients with Carcinoid Syndrome.

Purpose: The TELEACE study showed reductions in tumor size in patients with neuroendocrine tumors, receiving telotristat ethyl in US clinical practice. Here, we report progression-free survival, time to tumor progression, changes in carcinoid syndrome symptoms, and indictors of overall health. Patients and Methods: This was a retrospective, single arm, pre-post medical chart review of patients with locally advanced or metastatic neuroendocrine tumors and documented carcinoid syndrome receiving telotristat ethyl for at least 6 months. Patients with poorly differentiated tumors, mixed tumor types or conflicting clinical trial enrollment were excluded. Descriptive statistics, Kaplan-Meier and chi-square tests were used to evaluate PFS, tumor progression, changes in symptoms, body weight and ECOG performance status before and after telotristat ethyl initiation. Subgroup analyses were conducted in patients with the same pre- and post-telotristat ethyl background treatment. Results: Anonymized data for 200 patients were provided by 114 physicians; patients received telotristat ethyl for a median of 9 months. Median time to tumor progression was 39.8 months (IQR, 18.7-39.8); most had no tumor progression at 6 (92%) and 12 months (87%). Median progression-free survival was 23.7 months (17.8-39.8); most had progression-free survival at 6 (90%) and 12 months (80%). Results were consistent in the subgroup of 65 patients with the same pre/post background treatment. Nearly all patients had improved carcinoid syndrome symptoms, stable or improved weight and ECOG performance status. Conclusion: Patients showed improvements in clinical outcomes and indicators of overall health following treatment with telotristat ethyl in this exploratory pilot study, consistent with previously observed reductions in tumor size.
Authors
Metz, DC; Liu, E; Joish, VN; Huynh, L; Totev, TI; Duh, MS; Seth, K; Giacalone, S; Lapuerta, P; Morse, MA
MLA Citation
Metz, David C., et al. “Survival and Clinical Outcomes with Telotristat Ethyl in Patients with Carcinoid Syndrome.Cancer Manag Res, vol. 12, 2020, pp. 9713–19. Pubmed, doi:10.2147/CMAR.S276519.
URI
https://scholars.duke.edu/individual/pub1462499
PMID
33116830
Source
pubmed
Published In
Cancer Management and Research
Volume
12
Published Date
Start Page
9713
End Page
9719
DOI
10.2147/CMAR.S276519

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