A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab Plus PolyICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers
Study Details
Study Description
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 |
---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Phase 1, Cohort 1A IV Durvalumab + IT/IM polyICLC |
Drug: Durvalumab
Other Names:
Drug: Poly ICLC
Other Names:
|
Experimental: Phase 1, Cohort 1B IV Durvalumab + IV Tremelimumab + IT/IM polyICLC |
Drug: Durvalumab
Other Names:
Drug: Tremelimumab
Drug: Poly ICLC
Other Names:
|
Experimental: Phase 1, Cohort 1C IV Durvalumab + IT Tremelimumab + IT/IM polyICLC |
Drug: Durvalumab
Other Names:
Drug: Tremelimumab
Drug: Poly ICLC
Other Names:
|
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 Names:
Drug: Tremelimumab
Drug: Poly ICLC
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival (PFS) at 24 weeks [up to 24 weeks]
Analyzed by irRECIST
Secondary Outcome Measures
- Safety and tolerability [up to 15 months]
Adverse events according to CTCAE V4.03
- Clinical Efficacy by objective response rate (ORR) [up to 15 months]
assessed by irRECIST
- Clinical Efficacy by progression-free survival (PFS) [up to 15 months]
assessed by irRECIST
- Clinical Efficacy by overall survival (OS) [up to 15 months]
assessed by irRECIST
Eligibility Criteria
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
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Locally recurrent or metastatic breast cancer
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Sarcoma
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Merkel Cell Carcinoma (MCC)
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Cutaneous T cell Lymphoma (CTCL)
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Melanoma after failure of available therapies
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GU cancers with accessible metastases (e.g., bladder, renal)
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Any solid tumors with masses that are accessible
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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).
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Any number of prior systemic therapies.
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ECOG performance status 0-1.
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Laboratory parameters for vital functions should be in the normal range or not clinically significant.
Exclusion Criteria:
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Prior treatment with combination CTLA-4 and PD-1/PD-L1 blockade, with the exception of subjects with melanoma.
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Participants may not have been treated intratumorally with polyICLC.
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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 active 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.
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Active, suspected or prior documented autoimmune disease, clinically significant cardiovascular disease or clinically uncontrolled hypertension.
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History of pneumonitis or interstitial lung disease or any unresolved immune-related adverse events following prior biological therapy.
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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).
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Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who require drainage gastrostomy tube and/or parenteral hydration or nutrition.
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Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C positivity. Antibody to Hepatitis B or C without evidence of active infection may be allowed.
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History of severe allergic reactions to any unknown allergens or any components of the study drugs.
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Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
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History of allogeneic organ transplant.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Research Facility | Atlanta | Georgia | United States | 30322 |
2 | Research Facility | Lebanon | New Hampshire | United States | 03756 |
3 | Research Facility | Buffalo | New York | United States | 14263 |
4 | Research Facility | New York | New York | United States | 10029 |
5 | Research Facility | Cleveland | Ohio | United States | 44195 |
6 | Research Facility | Toledo | Ohio | United States | 43614 |
7 | Research Facility | Charlottesville | Virginia | United States | 22908 |
Sponsors and Collaborators
- Ludwig Institute for Cancer Research
- MedImmune LLC
- Cancer Research Institute, New York City
Investigators
- 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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- LUD2014-011