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.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||December 28, 2016||Phase 1/Phase 2||Interventional|
Primary Outcome 1 - Measure: To determine the recommended combination doses of the dosing regimen, based on assessment of toxicity and tolerability.
Primary Outcome 1 - Time Frame: 12 months
Primary Outcome 2 - Measure: Clinical Efficacy will be determined by objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) and will be assessed by irRECIST and RECIST1.1.
Primary Outcome 2 - Time Frame: up to 6 years
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
- 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. Performance status 0-1.
5. 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.
6. Age ≥ 18 years.
7. Able and willing to give valid written informed consent.
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. Unresolved irAEs following prior biological therapy, except that stable and managed
irAEs may be acceptable (e.g., hypothyroidism or hypopituitarism on appropriate
4. 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.
5. Subjects with clinically significant cardiovascular disease, including:
1. Uncontrolled hypertension, defined as systolic blood pressure (BP) > 150 mmHg or
diastolic BP > 90 mmHg.
2. Myocardial infarction or unstable angina within 6 months of the first date of
treatment on this study.
3. 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
4. Baseline ejection fraction ≤ 50% as assessed by echocardiogram or multi-gated
acquisition (MUGA) scan.
5. New York Heart Association (NYHA) Class II or higher congestive heart failure.
6. Grade 2 or higher peripheral ischemia [brief (< 24 hours) episode of ischemia
managed non-surgically and without permanent deficit].
6. History of pneumonitis or interstitial lung disease.
7. 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.
8. 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
9. Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who
require drainage gastrostomy tube and/or parenteral hydration or nutrition.
10. Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C positivity. Antibody to
Hepatitis B or C without evidence of active infection may be allowed.
11. History of severe allergic reactions to any unknown allergens or any components of the
12. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding
13. Participation in any other clinical trial involving another investigational agent
within 4 weeks prior to Day 1 of the study.
14. Mental impairment that may compromise the ability to give informed consent and comply
with the requirements of the study.
15. Lack of availability for immunological and clinical follow-up assessment.
16. 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.
17. Females of childbearing potential not using a medically acceptable means of
18. 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
19. History of allogenic organ transplant.
20. 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.)
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No
Name: Craig L Slingluff, Jr., MD
Role: Study Chair
Affiliation: University of Virginia
Name: Sunita Hack, MS
Atlanta, Georgia 30322
Buffalo, New York 14263
New York, New York 10029
Cleveland, Ohio 44195
Charlottesville, Virginia 22908
Emily H. Allred, PhD, CCRC