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A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab Plus PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers

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ClinicalTrials.gov Identifier: NCT02643303
Recruitment Status : Recruiting
First Posted : December 31, 2015
Last Update Posted : March 14, 2019
Sponsor:
Collaborators:
MedImmune LLC
Cancer Research Institute, New York City
Information provided by (Responsible Party):
Ludwig Institute for Cancer Research

Brief Summary:
This is an open-label, multicenter Phase 1/2 study of the CTLA-4 antibody, tremelimumab, and the PD-L1 antibody, durvalumab (MEDI4736), in combination with the tumor microenvironment (TME) modulator polyICLC, a TLR3 agonist, in subjects with advanced, measurable, biopsy-accessible cancers.

Condition or disease Intervention/treatment Phase
Head and Neck Squamous Cell Carcinoma Breast Cancer Sarcoma Merkel Cell Carcinoma Cutaneous T-Cell Lymphoma Melanoma Renal Cancer Bladder Cancer Prostate Cancer Testicular Cancer Solid Tumor Drug: Durvalumab Drug: Tremelimumab Drug: Poly ICLC Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab (MEDI4736) Plus the Toll-like Receptor Agonist PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers
Actual Study Start Date : December 28, 2016
Estimated Primary Completion Date : August 2022
Estimated Study Completion Date : August 2022


Arm Intervention/treatment
Experimental: Phase 1, Cohort 1A
IV Durvalumab + IT/IM polyICLC
Drug: Durvalumab
Other Name: MEDI4736

Drug: Poly ICLC
Other Name: Hiltonol

Experimental: Phase 1, Cohort 1B
IV Durvalumab + IV Tremelimumab + IT/IM polyICLC
Drug: Durvalumab
Other Name: MEDI4736

Drug: Tremelimumab
Drug: Poly ICLC
Other Name: Hiltonol

Experimental: Phase 1, Cohort 1C
IV Durvalumab + IT Tremelimumab + IT/IM polyICLC
Drug: Durvalumab
Other Name: MEDI4736

Drug: Tremelimumab
Drug: Poly ICLC
Other Name: Hiltonol

Experimental: Phase 2 Cohort
Once the recommended combination doses of the triplet dosing regimen has been determined in Cohort 1C, subsequent subjects will be enrolled into Cohort 2 to receive the recommended combination doses of both checkpoint antibodies in combination with polyICLC.
Drug: Durvalumab
Other Name: MEDI4736

Drug: Tremelimumab
Drug: Poly ICLC
Other Name: Hiltonol




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) at 24 weeks [ Time Frame: up to 24 weeks ]
    Analyzed by irRECIST


Secondary Outcome Measures :
  1. Safety and tolerability [ Time Frame: up to 15 months ]
    Adverse events according to CTCAE V4.03

  2. Clinical Efficacy by objective response rate (ORR) [ Time Frame: up to 15 months ]
    assessed by irRECIST

  3. Clinical Efficacy by progression-free survival (PFS) [ Time Frame: up to 15 months ]
    assessed by irRECIST

  4. Clinical Efficacy by overall survival (OS) [ Time Frame: up to 15 months ]
    assessed by irRECIST



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects must have histologic confirmation of advanced, biopsy-accessible, measurable cancers of the following histologies:

    • Non-viral-associated head and neck squamous cell carcinoma (HNSCC) or HPV-associated HNSCC after failure of prior therapy
    • Locally recurrent or metastatic breast cancer
    • Sarcoma
    • Merkel Cell Carcinoma (MCC)
    • Cutaneous T cell Lymphoma (CTCL)
    • Melanoma after failure of available therapies
    • GU cancers with accessible metastases (e.g., bladder, renal)
    • Any solid tumors with masses that are accessible
  2. Subjects with measurable disease, must have at least 2 lesions (1 measurable lesion and 1 biopsy/injectable lesion, which will not need to be measurable).
  3. Any number of prior systemic therapies.
  4. ECOG performance status 0-1.
  5. Laboratory parameters for vital functions should be in the normal range or not clinically significant.

Exclusion Criteria:

  1. Prior treatment with combination CTLA-4 and PD-1/PD-L1 blockade, with the exception of subjects with melanoma.
  2. Participants may not have been treated intratumorally with polyICLC.
  3. Subjects with history or evidence upon physical examination of central nervous system (CNS) disease, including primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or, within 6 months of the first date of treatment on this study, history of cerebrovascular accident (CVA, stroke), transient ischemic attack (TIA) or subarachnoid hemorrhage.
  4. Active, suspected or prior documented autoimmune disease, clinically significant cardiovascular disease or clinically uncontrolled hypertension.
  5. History of pneumonitis or interstitial lung disease or any unresolved immune-related adverse events following prior biological therapy.
  6. Other malignancy within 2 years prior to entry into the study, except for those treated with surgical therapy only (e.g., localized low-grade cervical or prostate cancers).
  7. Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who require drainage gastrostomy tube and/or parenteral hydration or nutrition.
  8. Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C positivity. Antibody to Hepatitis B or C without evidence of active infection may be allowed.
  9. History of severe allergic reactions to any unknown allergens or any components of the study drugs.
  10. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
  11. History of allogeneic organ transplant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02643303


Contacts
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Contact: Kristen Aufiero Ramirez 212-450-1515 clintrialinformation@licr.org

Locations
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United States, Georgia
Research Facility Recruiting
Atlanta, Georgia, United States, 30322
United States, New York
Research Facility Recruiting
Buffalo, New York, United States, 14263
Research Facility Recruiting
New York, New York, United States, 10029
United States, Ohio
Research Facility Recruiting
Cleveland, Ohio, United States, 44195
Contact: Shelley Robinson       robinss@ccf.org   
United States, Virginia
Research Facility Recruiting
Charlottesville, Virginia, United States, 22908
Contact: Emily H. Allred, PhD, CCRC       eh4m@virginia.edu   
Sponsors and Collaborators
Ludwig Institute for Cancer Research
MedImmune LLC
Cancer Research Institute, New York City
Investigators
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Study Chair: Craig L Slingluff, Jr., MD University of Virginia
Study Chair: Nina Bhardwaj, MD, PhD Tisch Cancer Institute Ichan School of Medicine at Mount Sinai

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Responsible Party: Ludwig Institute for Cancer Research
ClinicalTrials.gov Identifier: NCT02643303     History of Changes
Other Study ID Numbers: LUD2014-011
First Posted: December 31, 2015    Key Record Dates
Last Update Posted: March 14, 2019
Last Verified: March 2019

Keywords provided by Ludwig Institute for Cancer Research:
Durvalumab
MEDI4736
Tremelimumab
PolyICLC
Hiltonol
Locally Recurrent Breast Cancer
Metastatic Melanoma
In Situ
CTLA-4 Antibody
PD-L1 Antibody
TLR3 Agonist
CTCL

Additional relevant MeSH terms:
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Carcinoma
Melanoma
Carcinoma, Squamous Cell
Urinary Bladder Neoplasms
Lymphoma, T-Cell
Squamous Cell Carcinoma of Head and Neck
Lymphoma, T-Cell, Cutaneous
Kidney Neoplasms
Carcinoma, Renal Cell
Carcinoma, Merkel Cell
Testicular Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Nevi and Melanomas
Neoplasms, Squamous Cell
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Lymphoma, Non-Hodgkin
Lymphoma
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders