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

NCT02643303

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.

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Merkel Cell Carcinoma
  • Primary Cutaneous T Cell Non-Hodgkin Lymphoma
  • Renal Cell Carcinoma
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: LUD2014-011
  • NCT ID: NCT02643303

Conditions

  • 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

Interventions

DrugSynonymsArms
DurvalumabMEDI4736Phase 1, Cohort 1A
TremelimumabPhase 1, Cohort 1B
Poly ICLCHiltonolPhase 1, Cohort 1A

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Phase 1, Cohort 1AExperimentalIV Durvalumab + IT/IM polyICLC
  • Durvalumab
  • Poly ICLC
Phase 1, Cohort 1BExperimentalIV Durvalumab + IV Tremelimumab + IT/IM polyICLC
  • Durvalumab
  • Tremelimumab
  • Poly ICLC
Phase 1, Cohort 1CExperimentalIV Durvalumab + IT Tremelimumab + IT/IM polyICLC
  • Durvalumab
  • Tremelimumab
  • Poly ICLC
Phase 2 CohortExperimentalOnce 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.
  • Durvalumab
  • Tremelimumab
  • Poly ICLC

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS) at 24 weeks
Time Frame:up to 24 weeks
Safety Issue:
Description:Analyzed by irRECIST

Secondary Outcome Measures

Measure:Safety and tolerability
Time Frame:up to 15 months
Safety Issue:
Description:Adverse events according to CTCAE V4.03
Measure:Clinical Efficacy by objective response rate (ORR)
Time Frame:up to 15 months
Safety Issue:
Description:assessed by irRECIST
Measure:Clinical Efficacy by progression-free survival (PFS)
Time Frame:up to 15 months
Safety Issue:
Description:assessed by irRECIST
Measure:Clinical Efficacy by overall survival (OS)
Time Frame:up to 15 months
Safety Issue:
Description:assessed by irRECIST

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Ludwig Institute for Cancer Research

Trial Keywords

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

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