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

Sponsor

Ludwig Institute for Cancer Research (Other)

Overall Status

Completed

CT.gov ID

NCT02643303

Collaborator

MedImmune LLC (Industry), Cancer Research Institute, New York City (Other)

Enrollment

Locations

Arms

61.9

Actual Duration (Months)

8.3

Patients Per Site

0.1

Patients Per Site Per Month

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
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

Study Design

Study Type:

Interventional

Actual Enrollment :

58 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 :

Dec 28, 2016

Actual Primary Completion Date :

Feb 23, 2022

Actual Study Completion Date :

Feb 23, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase 1, Cohort 1A IV Durvalumab + IT/IM polyICLC	Drug: Durvalumab Other Names: MEDI4736 Drug: Poly ICLC Other Names: Hiltonol
Experimental: Phase 1, Cohort 1B IV Durvalumab + IV Tremelimumab + IT/IM polyICLC	Drug: Durvalumab Other Names: MEDI4736 Drug: Tremelimumab Drug: Poly ICLC Other Names: Hiltonol
Experimental: Phase 1, Cohort 1C IV Durvalumab + IT Tremelimumab + IT/IM polyICLC	Drug: Durvalumab Other Names: MEDI4736 Drug: Tremelimumab Drug: Poly ICLC Other Names: 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 Names: MEDI4736 Drug: Tremelimumab Drug: Poly ICLC Other Names: Hiltonol

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

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 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.
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.

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