A Study of Tremelimumab and IV Durvalumab Plus Poly-ICLC in Subjects With Biopsy-accessible Cancers

November 17, 2022 updated by: Ludwig Institute for Cancer Research

A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab (MEDI4736) Plus the Toll-like Receptor Agonist Poly-ICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers

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 poly-ICLC, a TLR3 agonist, in subjects with advanced, measurable, biopsy-accessible cancers.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is an open-label, multicenter, Phase 1/2 study of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, tremelimumab, and the programmed cell death ligand-1 (PD-L1) antibody, durvalumab (MEDI4736), in combination with the tumor microenvironment (TME) modulator poly-ICLC, a toll-like receptor 3 (TLR3) agonist, in subjects with advanced, measurable, biopsy-accessible cancers. Subjects will receive intratumoral and intramuscular (IM) administration of poly-ICLC and intravenous (IV) administration of durvalumab, together with either IV or intratumoral administration of tremelimumab. The study will be conducted in 2 phases.

Phase 1: There will be enrollment to 3 subject cohorts in Phase 1, with staggered initiation of enrollment.

  • Cohort 1A: IV Durvalumab + Intratumoral/IM Poly-ICLC. After safety is demonstrated in the first 3-6 subjects in Cohort 1A, Cohorts 1B and 1C will open to enrollment.
  • Cohort 1B: IV Durvalumab + IV Tremelimumab + Intratumoral/IM Poly-ICLC.
  • Cohort 1C: IV Durvalumab + Intratumoral Tremelimumab + Intratumoral/IM Poly-ICLC.

Phase 2: Upon determination of the recommended combination dose in Cohort 1C, up to 66 evaluable subjects will be treated in Phase 2. Up to 6 subjects will be initially enrolled by tumor type (head and neck squamous cell carcinoma, locally recurrent or metastatic breast cancer, sarcoma, Merkel cell carcinoma, cutaneous T-cell lymphoma, melanoma after failure of available therapies, genitourinary cancers and solid tumors with accessible metastases). Subjects enrolled in Cohort 1C will be included in Phase 2 in the applicable tumor type. Data from all subjects in each Phase 2 tumor type will be reviewed for safety/efficacy to select up to 3 tumor types that demonstrate an efficacy signal, defined as at least 1 of 6 subjects within a tumor type who achieve a partial response (PR) or complete response (CR) by immune-related RECIST (irRECIST) or RECIST 1.1, or stable disease (SD) for at least 6 months. Up to 6 additional subjects in each of the selected tumor types may be enrolled in the expansion.

Study Type

Interventional

Enrollment (Actual)

58

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Research Facility
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Research Facility
    • New York
      • Buffalo, New York, United States, 14263
        • Research Facility
      • New York, New York, United States, 10029
        • Research Facility
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Research Facility
      • Toledo, Ohio, United States, 43614
        • Research Facility
    • Virginia
      • Charlottesville, Virginia, United States, 22908
        • Research Facility

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 human papillomavirus (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
    • Genitourinary (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 does not need to be measurable).
  3. Any number of prior systemic therapies.
  4. Eastern Cooperative Oncology Group (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 poly-ICLC.
  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1, Cohort 1A
Subjects received durvalumab (1500 mg IV every 4 weeks [Q4W] for 12 cycles). Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi®
Drug: Poly-ICLC
Other Names:
  • Hiltonol®
Experimental: Phase 1, Cohort 1B

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (75 mg IV Q4W for the first 4 cycles).

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi®
Drug: Tremelimumab
Drug: Poly-ICLC
Other Names:
  • Hiltonol®
Experimental: Cohort 1C + Phase 2; Head + Neck Squamous Cell Carcinoma

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (10 mg) intratumorally on days 1, 8, and 15 of Cycle 1, days 1 and 15 of Cycle 2 and day 1 of Cycles 3 and 4.

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi®
Drug: Tremelimumab
Drug: Poly-ICLC
Other Names:
  • Hiltonol®
Experimental: Cohort 1C + Phase 2; Locally Recurrent or Metastatic Breast Cancer

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (10 mg) intratumorally on days 1, 8, and 15 of Cycle 1, days 1 and 15 of Cycle 2 and day 1 of Cycles 3 and 4.

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi®
Drug: Tremelimumab
Drug: Poly-ICLC
Other Names:
  • Hiltonol®
Experimental: Cohort 1C + Phase 2; Sarcoma

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (10 mg) intratumorally on days 1, 8, and 15 of Cycle 1, days 1 and 15 of Cycle 2 and day 1 of Cycles 3 and 4.

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi®
Drug: Tremelimumab
Drug: Poly-ICLC
Other Names:
  • Hiltonol®
Experimental: Cohort 1C + Phase 2; Merkel Cell Carcinoma

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (10 mg) intratumorally on days 1, 8, and 15 of Cycle 1, days 1 and 15 of Cycle 2 and day 1 of Cycles 3 and 4.

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi®
Drug: Tremelimumab
Drug: Poly-ICLC
Other Names:
  • Hiltonol®
Experimental: Cohort 1C + Phase 2; Cutaneous T-cell Lymphoma

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (10 mg) intratumorally on days 1, 8, and 15 of Cycle 1, days 1 and 15 of Cycle 2 and day 1 of Cycles 3 and 4.

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi®
Drug: Tremelimumab
Drug: Poly-ICLC
Other Names:
  • Hiltonol®
Experimental: Cohort 1C + Phase 2; Melanoma After Failure of Available Therapies

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (10 mg) intratumorally on days 1, 8, and 15 of Cycle 1, days 1 and 15 of Cycle 2 and day 1 of Cycles 3 and 4.

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi®
Drug: Tremelimumab
Drug: Poly-ICLC
Other Names:
  • Hiltonol®
Experimental: Cohort 1C + Phase 2; Genitourinary Cancers with Accessible Metastases

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (10 mg) intratumorally on days 1, 8, and 15 of Cycle 1, days 1 and 15 of Cycle 2 and day 1 of Cycles 3 and 4.

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi®
Drug: Tremelimumab
Drug: Poly-ICLC
Other Names:
  • Hiltonol®
Experimental: Cohort 1C + Phase 2; Solid Tumors with Accessible Masses

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (10 mg) intratumorally on days 1, 8, and 15 of Cycle 1, days 1 and 15 of Cycle 2 and day 1 of Cycles 3 and 4.

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.
Drug: Durvalumab
Other Names:
  • MEDI4736
  • Imfinzi®
Drug: Tremelimumab
Drug: Poly-ICLC
Other Names:
  • Hiltonol®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Time Frame: up to 15 months
Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through 90 days after the last dose of study treatment. Treatment-emergent AEs were those that occurred or worsened after administration of the first dose of study treatment.
up to 15 months
Number of Subjects With Best Overall Tumor Response by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Time Frame: up to 15 months
Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment. Per irRECIST, measurable lesions were categorized as follows: Complete Response (irCR): Complete disappearance of all target lesions; Partial Response (irPR): ≥ 30% decrease from baseline in the Total Measured Tumor Burden (TMTB); Progressive Disease (irPD): ≥ 20% increase from nadir in Total Measured Tumor Burden (TMTB); Stable Disease (irSD): not meeting above criteria.
up to 15 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Median Progression-free Survival (PFS) by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method
Time Frame: up to 15 months

Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment.

PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression did not occur. Per irRECIST, Progressive Disease (irPD) was defined as a ≥ 20% increase from nadir in the Total Measured Tumor Burden (TMTB).
up to 15 months
Overall Disease Control Rate as Measured by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)
Time Frame: Up to 24 weeks

Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment. Per irRECIST, measurable lesions were categorized as follows: Complete Response (irCR): Complete disappearance of all target lesions; Partial Response (irPR): ≥ 30% decrease from baseline in the Total Measurable Tumor Burden (TMTB); Progressive Disease (irPD): ≥ 20% increase from nadir in Total Measured Tumor Burden (TMTB); Stable Disease (irSD): not meeting above criteria.

Overall Disease Control Rate was defined as the percentage of subjects who had irSD for at least 6 months, or irPR or irCR over a period of at least 4 weeks. Subjects who dropped out prior to meeting the responder criteria were considered non-responders.
Up to 24 weeks
Number of Subjects With Best Overall Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time Frame: up to 13 months
Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment. Per RECIST 1.1, target lesions are categorized as follows: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions or presence of new lesions; Stable Disease (SD): small changes that did not meet above criteria.
up to 13 months
Median PFS by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as Estimated Using the Kaplan-Meier Method
Time Frame: Up to 15 months

Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment.

PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression according to RECIST 1.1 or to the date of death, if disease progression did not occur. Per RECIST 1.1, Progressive disease (PD) was defined as a ≥ 20% increase in the sum of the longest diameter of target lesions or the presence of new lesions.
Up to 15 months
Overall Disease Control Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
Time Frame: up to 24 weeks

Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment. Per RECIST 1.1, target lesions are categorized as follows: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions or presence of new lesions; Stable Disease (SD): small changes that did not meet above criteria.

Overall Disease Control Rate was defined as the percentage of subjects who had SD for at least 6 months, or PR or CR over a period of at least 4 weeks. Subjects who dropped out prior to meeting the responder criteria were considered non-responders.
up to 24 weeks
Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method
Time Frame: up to 5 years
After completion of treatment, all subjects were followed for survival every 3 months for 2 years after completion of treatment; then every 6 months until 5 years from study entry; then yearly until 10 years from study entry. OS was measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up were censored on the date when they were last known to be alive. Per protocol amendment 6.0, all post study follow-up for the collection of survival data was discontinued as of February 28, 2022. The last collection of survival data was on February 23, 2022.
up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ludwig Institute for Cancer Research

Collaborators

Cancer Research Institute, New York City
MedImmune LLC

Investigators

  • Study Chair: Craig L Slingluff, Jr., MD, University of Virginia
  • Study Chair: Nina Bhardwaj, MD, PhD, Tisch Cancer Institute Icahn School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 28, 2016

Primary Completion (Actual)

February 23, 2022

Study Completion (Actual)

February 23, 2022

Study Registration Dates

First Submitted

December 18, 2015

First Submitted That Met QC Criteria

December 28, 2015

First Posted (Estimate)

December 31, 2015

Study Record Updates

Last Update Posted (Actual)

December 2, 2022

Last Update Submitted That Met QC Criteria

November 17, 2022

Last Verified

November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LUD2014-011

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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