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

Status: Active

Description

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.

Eligibility Criteria

Inclusion Criteria

  • 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
  • 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).
  • Any number of prior systemic therapies.
  • ECOG performance status 0-1.
  • Laboratory parameters for vital functions should be in the normal range or not clinically significant.

Exclusion Criteria

  • Prior treatment with combination CTLA-4 and PD-1/PD-L1 blockade, with the exception of subjects with melanoma.
  • Participants may not have been treated intratumorally with polyICLC.
  • 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.
  • Active, suspected or prior documented autoimmune disease, clinically significant cardiovascular disease or clinically uncontrolled hypertension.
  • History of pneumonitis or interstitial lung disease or any unresolved immune-related adverse events following prior biological therapy.
  • 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).
  • Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who require drainage gastrostomy tube and/or parenteral hydration or nutrition.
  • Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C positivity. Antibody to Hepatitis B or C without evidence of active infection may be allowed.
  • History of severe allergic reactions to any unknown allergens or any components of the study drugs.
  • Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
  • History of allogeneic organ transplant.

Locations & Contacts

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Name Not Available

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: In review
Name Not Available

New York

Buffalo
Roswell Park Cancer Institute
Status: Active
Name Not Available
New York
Icahn School of Medicine at Mount Sinai
Status: Active
Name Not Available

Ohio

Cleveland
Case Comprehensive Cancer Center
Status: Active
Name Not Available

Virginia

Charlottesville
University of Virginia Cancer Center
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Ludwig Institute for Cancer Research

Trial IDs

Primary ID LUD2014-011
Secondary IDs NCI-2017-01766
Clinicaltrials.gov ID NCT02643303