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

• ClinicalTrials.gov Identifier: NCT02643303
• Recruitment Status: Completed
• First Posted: December 31, 2015
• Last Update Posted: March 3, 2022
• Sponsor: Ludwig Institute for Cancer Research
• Collaborators: MedImmune LLC; Cancer Research Institute, New York City
• Information provided by (Responsible Party): Ludwig Institute for Cancer Research

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 (Clinical Trial)
• 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: December 28, 2016
• Actual Primary Completion Date: February 23, 2022
• Actual Study Completion Date: February 23, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS) at 24 weeks [ Time Frame: up to 24 weeks ]
   Analyzed by irRECIST

Secondary Outcome Measures :

1. Safety and tolerability [ Time Frame: up to 15 months ]
   Adverse events according to CTCAE V4.03
2. Clinical Efficacy by objective response rate (ORR) [ Time Frame: up to 15 months ]
   assessed by irRECIST
3. Clinical Efficacy by progression-free survival (PFS) [ Time Frame: up to 15 months ]
   assessed by irRECIST
4. Clinical Efficacy by overall survival (OS) [ Time Frame: up to 15 months ]
   assessed by irRECIST

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

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
   • 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
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. ECOG performance status 0-1.
5. Laboratory parameters for vital functions should be in the normal range or not clinically significant.

Exclusion Criteria:

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. 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.
4. Active, suspected or prior documented autoimmune disease, clinically significant cardiovascular disease or clinically uncontrolled hypertension.
5. History of pneumonitis or interstitial lung disease or any unresolved immune-related adverse events following prior biological therapy.
6. 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).
7. Subjects with clinical symptoms or signs of gastrointestinal obstruction and/or who require drainage gastrostomy tube and/or parenteral hydration or nutrition.
8. Known immunodeficiency or HIV, Hepatitis B, or Hepatitis C positivity. Antibody to Hepatitis B or C without evidence of active infection may be allowed.
9. History of severe allergic reactions to any unknown allergens or any components of the study drugs.
10. Other serious illnesses (e.g., serious infections requiring antibiotics, bleeding disorders).
11. History of allogeneic organ transplant.

Contacts and Locations

Locations

United States, Georgia

Research Facility

Atlanta, Georgia, United States, 30322

United States, New Hampshire

Research Facility

Lebanon, New Hampshire, United States, 03756

United States, New York

Research Facility

Buffalo, New York, United States, 14263

Research Facility

New York, New York, United States, 10029

United States, Ohio

Research Facility

Cleveland, Ohio, United States, 44195

Research Facility

Toledo, Ohio, United States, 43614

United States, Virginia

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

More Information

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT02643303
• Other Study ID Numbers: LUD2014-011
• First Posted: December 31, 2015
• Last Update Posted: March 3, 2022
• Last Verified: March 2022

Keywords provided by Ludwig Institute for Cancer Research:

Durvalumab; MEDI4736; Tremelimumab; PolyICLC; Hiltonol; Locally Recurrent Breast Cancer; Metastatic Melanoma; In Situ; CTLA-4 Antibody; PD-L1 Antibody; TLR3 Agonist; CTCL

Additional relevant MeSH terms:

Carcinoma, Merkel Cell; Carcinoma; Melanoma; Squamous Cell Carcinoma of Head and Neck; Lymphoma, T-Cell, Cutaneous; Kidney Neoplasms; Testicular Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Urogenital Neoplasms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Carcinoma, Squamous Cell; Urologic Neoplasms; Urologic Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Head and Neck Neoplasms; Kidney Diseases