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

NCT02643303 | Completed Phase 1 Results FDA Drug

• 1 other identifier: LUD2014-011
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 7

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

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

Keywords

Durvalumab; MEDI4736; Tremelimumab; Poly-ICLC; Hiltonol®; Breast Cancer; Melanoma; In Situ; CTLA-4 Antibody; PD-L1 Antibody; TLR3 Agonist; CTCL; Imfinzi®

Outcome Measures

Primary Outcomes (2)

• Number of Subjects With Treatment-emergent Adverse Events (TEAEs)

  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)

  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 Outcomes (6)

• Median Progression-free Survival (PFS) by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method

  up to 15 months

• Overall Disease Control Rate as Measured by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)

  Up to 24 weeks

• Number of Subjects With Best Overall Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  up to 13 months

• Median PFS by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as Estimated Using the Kaplan-Meier Method

  Up to 15 months

• Overall Disease Control Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

  up to 24 weeks

Study Arms (10)

Phase 1, Cohort 1A

EXPERIMENTAL

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; Drug: Poly-ICLC

Phase 1, Cohort 1B

EXPERIMENTAL

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; Drug: Tremelimumab; Drug: Poly-ICLC

Cohort 1C + Phase 2; Head + Neck Squamous Cell Carcinoma

EXPERIMENTAL

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; Drug: Tremelimumab; Drug: Poly-ICLC

Cohort 1C + Phase 2; Locally Recurrent or Metastatic Breast Cancer

EXPERIMENTAL

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; Drug: Tremelimumab; Drug: Poly-ICLC

Cohort 1C + Phase 2; Sarcoma

EXPERIMENTAL

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; Drug: Tremelimumab; Drug: Poly-ICLC

Cohort 1C + Phase 2; Merkel Cell Carcinoma

EXPERIMENTAL

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; Drug: Tremelimumab; Drug: Poly-ICLC

Cohort 1C + Phase 2; Cutaneous T-cell Lymphoma

EXPERIMENTAL

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; Drug: Tremelimumab; Drug: Poly-ICLC

Cohort 1C + Phase 2; Melanoma After Failure of Available Therapies

EXPERIMENTAL

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; Drug: Tremelimumab; Drug: Poly-ICLC

Cohort 1C + Phase 2; Genitourinary Cancers with Accessible Metastases

EXPERIMENTAL

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; Drug: Tremelimumab; Drug: Poly-ICLC

Cohort 1C + Phase 2; Solid Tumors with Accessible Masses

EXPERIMENTAL

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; Drug: Tremelimumab; Drug: Poly-ICLC

Interventions

Durvalumab DRUG

Also known as: MEDI4736, Imfinzi®

Cohort 1C + Phase 2; Cutaneous T-cell Lymphoma; Cohort 1C + Phase 2; Genitourinary Cancers with Accessible Metastases; Cohort 1C + Phase 2; Head + Neck Squamous Cell Carcinoma; Cohort 1C + Phase 2; Locally Recurrent or Metastatic Breast Cancer; Cohort 1C + Phase 2; Melanoma After Failure of Available Therapies; Cohort 1C + Phase 2; Merkel Cell Carcinoma; Cohort 1C + Phase 2; Sarcoma; Cohort 1C + Phase 2; Solid Tumors with Accessible Masses; Phase 1, Cohort 1A; Phase 1, Cohort 1B

Tremelimumab DRUG

Cohort 1C + Phase 2; Cutaneous T-cell Lymphoma; Cohort 1C + Phase 2; Genitourinary Cancers with Accessible Metastases; Cohort 1C + Phase 2; Head + Neck Squamous Cell Carcinoma; Cohort 1C + Phase 2; Locally Recurrent or Metastatic Breast Cancer; Cohort 1C + Phase 2; Melanoma After Failure of Available Therapies; Cohort 1C + Phase 2; Merkel Cell Carcinoma; Cohort 1C + Phase 2; Sarcoma; Cohort 1C + Phase 2; Solid Tumors with Accessible Masses; Phase 1, Cohort 1B

Poly-ICLC DRUG

Also known as: Hiltonol®

Cohort 1C + Phase 2; Cutaneous T-cell Lymphoma; Cohort 1C + Phase 2; Genitourinary Cancers with Accessible Metastases; Cohort 1C + Phase 2; Head + Neck Squamous Cell Carcinoma; Cohort 1C + Phase 2; Locally Recurrent or Metastatic Breast Cancer; Cohort 1C + Phase 2; Melanoma After Failure of Available Therapies; Cohort 1C + Phase 2; Merkel Cell Carcinoma; Cohort 1C + Phase 2; Sarcoma; Cohort 1C + Phase 2; Solid Tumors with Accessible Masses; Phase 1, Cohort 1A; Phase 1, Cohort 1B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).
• Any number of prior systemic therapies.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Laboratory parameters for vital functions should be in the normal range or not clinically significant.

You may not qualify if:

• 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 poly-ICLC.
• 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.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• MedImmune LLC: collaborator
• Cancer Research Institute, New York City: collaborator

Study Sites (7)

Research Facility

Atlanta, Georgia, 30322, United States

Location

Research Facility

Lebanon, New Hampshire, 03756, United States

Location

Research Facility

Buffalo, New York, 14263, United States

Location

Research Facility

New York, New York, 10029, United States

Location

Research Facility

Cleveland, Ohio, 44195, United States

Location

Research Facility

Toledo, Ohio, 43614, United States

Location

Research Facility

Charlottesville, Virginia, 22908, United States

Location

Related Publications (2)

• Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

  PMID: 19097774 BACKGROUND

• Bohnsack O, Hoos A, Ludajic K. Adaptation of the immune related response criteria: irRECIST. Ann Oncol. 2014 Sep;25(suppl 4):iv361-iv72 [Abstract 4958]. doi: 10.1093/annonc/mdu342.23.

  BACKGROUND

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Breast Neoplasms; Sarcoma; Carcinoma, Merkel Cell; Lymphoma, T-Cell, Cutaneous; Melanoma; Kidney Neoplasms; Urinary Bladder Neoplasms; Prostatic Neoplasms; Testicular Neoplasms

Interventions

durvalumab; tremelimumab; poly ICLC

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Connective and Soft Tissue; Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Adenocarcinoma; Neoplasms, Nerve Tissue; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Nevi and Melanomas; Skin Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Genital Diseases; Prostatic Diseases; Endocrine Gland Neoplasms; Endocrine System Diseases; Testicular Diseases; Gonadal Disorders

Results Point of Contact

• Title: Jonathan Skipper
• Organization: Ludwig Institute for Cancer Research

jskipper@lcr.org

12124501539

Study Officials

• Craig L Slingluff, Jr., MD

  University of Virginia

  STUDY CHAIR

• Nina Bhardwaj, MD, PhD

  Tisch Cancer Institute Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In Phase 1, Cohort 1A was opened first and after the safety of durvalumab and poly-ICLC was demonstrated, Cohorts 1B and 1C were open in parallel. In Phase 2, all tumor types were opened in parallel, and subjects included in Cohort 1C were included and reported in their respective tumor type in Phase 2.

Study Record Dates

• First Submitted: December 18, 2015
• First Posted: December 31, 2015
• Study Start: December 28, 2016
• Primary Completion: February 23, 2022
• Study Completion: February 23, 2022
• Last Updated: December 2, 2022
• Results First Posted: December 2, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)