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.
  • Performance status 0-1.
  • Laboratory parameters:
  • Absolute neutrophil count (ANC) ≥ 1000/mm3;
  • Platelets ≥ 100,000/mm3;
  • Hemoglobin (Hgb) ≥ 9 g/dL;
  • Hgb-A1C ≤ 7.5%;
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN);
  • Bilirubin ≤ 2.5 × ULN (≤ 4 × ULN for subjects with Gilbert's disease);
  • Alkaline phosphatase ≤ 2.5 × ULN;
  • Creatinine ≤ 1.5 × ULN.
  • Age ≥ 18 years.
  • Able and willing to give valid written informed consent.

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.
  • Unresolved irAEs following prior biological therapy, except that stable and managed irAEs may be acceptable (e.g., hypothyroidism or hypopituitarism on appropriate replacement).
  • 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.
  • Subjects with clinically significant cardiovascular disease, including:
  • Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mmHg or diastolic BP > 90 mmHg.
  • Myocardial infarction or unstable angina within 6 months of the first date of treatment on this study.
  • History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic medications, except for atrial fibrillation that is well controlled with anti arrhythmic medication.
  • Baseline ejection fraction ≤ 50% as assessed by echocardiogram or multi-gated acquisition (MUGA) scan.
  • New York Heart Association (NYHA) Class II or higher congestive heart failure.
  • Grade 2 or higher peripheral ischemia [brief (< 24 hours) episode of ischemia managed non-surgically and without permanent deficit].
  • History of pneumonitis or interstitial lung disease.
  • Active, suspected or prior documented autoimmune disease (including but not restricted to inflammatory bowel disease, celiac disease, Wegner's granulomatosis and Hashimoto's thyroiditis, etc.). Participants with vitiligo, alopecia, type I diabetes mellitus, residual hypothyroidism (e.g. following Hashimoto syndrome) due to autoimmune condition only requiring hormone replacement, psoriasis or any chronic skin condition not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Subjects without active disease in the last 5 years may be included but only after consulting with the study physician. Subjects with celiac disease controlled by diet alone may also be included.
  • 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).
  • Participation in any other clinical trial involving another investigational agent within 4 weeks prior to Day 1 of the study.
  • Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
  • Lack of availability for immunological and clinical follow-up assessment.
  • Women of child bearing potential who are pregnant as evidenced by positive serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) or nursing.
  • Females of childbearing potential not using a medically acceptable means of contraception.
  • Any condition that, in the clinical judgment of the treating physician, is likely to interfere with the interpretability of the data or to prevent the subject from complying with any aspect of the protocol or that may put the subject at unacceptable risk.
  • History of allogenic organ transplant.
  • Subjects must not donate blood while on study and for at least 90 days following the last dose of durvalumab treatment or for 6 months after the last dose of tremelimumab (whichever is longer.)

Locations & Contacts

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
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