A Dose Escalation and Cohort Expansion Study of Anti-CD27 (Varlilumab) and Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors

December 5, 2019 updated by: Celldex Therapeutics

A Phase l/ll Dose Escalation and Cohort Expansion Study of the Safety, Tolerability and Efficacy of Anti-CD27 Antibody (Varlilumab) Administered in Combination With Anti-PD-1 (Nivolumab) in Advanced Refractory Solid Tumors

This is a study to determine the clinical benefit (how well the drug works), safety, and tolerability of combining varlilumab and nivolumab (also known as Opdivo® , BMS-936558). Both drugs target the immune system and may act to promote anti-cancer effects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Varlilumab is a fully human monoclonal antibody that binds to a molecule called CD27 found on certain immune cells and may act to promote anti-tumor effects.

Nivolumab is a fully human monoclonal antibody that binds to a molecule called PD-1 on immune cells and promotes anti-tumor effects.

Eligible patients that enroll in the dose escalation portion of the study will be assigned to one of three dose levels of varlilumab in combination with 3 mg/kg of nivolumab. The first phase of the study will test the safety profile of the combination and determine which dose will be studied in Phase ll of the overall study.

During Phase ll, depending on cancer type, groups of patients will be enrolled and receive varlilumab at a dose of either 3 mg/kg every 2 weeks, 3 mg/kg every 12 weeks, or 0.3 mg/kg every 4 weeks in combination with nivolumab at 240 mg.

All patients enrolled in the study will be closely monitored to determine if there is response to the treatment as well as for any side effects that may occur.

Study Type

Interventional

Enrollment (Actual)

175

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
    • Arizona
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center
    • California
      • Palo Alto, California, United States, 94304
        • The Stanford Center for Clinical and Translational Education and Research
      • San Francisco, California, United States, 94115
        • UCSF Helen Diller Family Comprehensive Cancer Center
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Medical Center
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Smilow Cancer Hospital at Yale University Cancer Center
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Georgetown University
      • Washington, District of Columbia, United States, 20037
        • George Washington University School of Medicine and Health Sciences
    • Florida
      • Miami Beach, Florida, United States, 33140
        • Mount Sinai Medical Center
    • Georgia
      • Marietta, Georgia, United States, 30060
        • Northwest Georgia Oncology Centers PC
    • Indiana
      • Fort Wayne, Indiana, United States, 46845
        • Parkview Research Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Barbara Ann Karmanos Cancer Institute
    • New York
      • New York, New York, United States, 10032
        • Columbia University Medical Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10016
        • Laura and Isaac Perlmutter Cancer Center
    • North Carolina
      • Winston-Salem, North Carolina, United States, 27157
        • Wake Forest Baptist Health
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Health & Services
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Inova Schar Cancer Institute Research

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

Key Inclusion Criteria:

  1. Histologically-diagnosed advanced (unresectable and/or metastatic) Non-small Cell Lung Cancer (Phase l only), Melanoma (Phase l only), Colorectal, Head and Neck SCC (squamous cell carcinoma), Ovarian Cancer, Glioblastoma or Renal Cell Carcinoma.

    • 1a. Head and Neck

    Stage III/IV squamous cell carcinoma; Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant, primary, recurrent or metastatic setting (or within 9 months if the patient received > 1 platinum-based chemotherapy regimen in the metastatic setting). Active brain metastases or leptomeningeal metastases are excluded; nasopharyngeal cancer, confirmed recurrent or metastatic carcinoma of the nasopharynx and salivary gland or non-squamous histologies are also excluded.

    • 1b. Ovarian

    Recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal carcinoma requiring original or subsequent relapse histologic documentation. A platinum-taxane based chemotherapy regimen as frontline therapy must have been completed.

    Any histologic diagnosis of borderline, low malignant potential epithelial carcinoma are excluded.

    • 1c. Colorectal Cancer -Enrollment Completed

    Metastatic or recurrent; prior treatment progression during, after, or intolerant following the last administration of approved standard therapies (required therapies apply).

    • 1d. Glioblastoma -Enrollment Completed

    Have histologically confirmed World Health Organization Grade IV malignant glioma (glioblastoma).

    • Previous first line therapy with at least radiotherapy and temozolomide.
    • Participants must have shown unequivocal evidence of tumor progression.
    • More than one relapse, secondary glioblastoma and prior treatment with bevacizumab are excluded.

    An interval of at least 12 weeks from the completion of radiation therapy to start of study treatment is required.

    • 1e. Renal Cell Carcinoma

    Have histologically confirmed diagnosis of predominant clear cell renal cell carcinoma.

    • Must have received 1 or 2 prior anti-angiogenic therapies.
    • No more than 5 total previous regimens of systemic therapy, including cytokines and cytotoxic chemotherapy.
    • Disease progression during or after the last treatment regimen and within 6 months before study entry.
  2. No more than 5 prior anticancer regimens for advanced (recurrent, locally advanced or metastatic) disease except for patients with GBM which must have first recurrence of GBM by diagnostic biopsy or contrast enhanced magnetic resonance imaging (MRI).
  3. Measurable (target) disease.
  4. Life expectancy ≥ 12 weeks.
  5. If of childbearing potential (male or female), agree to practice an effective form of contraception during study treatment and for at least 23 weeks after for female and 31 weeks after for male following last treatment dose.

Key Exclusion Criteria:

  1. History of severe hypersensitivity reactions to other monoclonal antibodies.
  2. Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody.
  3. Receipt of anti-CTLA-4 or anti-CD27 antibody within 3 months prior to the planned start of study treatment.
  4. Use of any monoclonal based therapies within 2-4 weeks prior to the first dose of study treatment.
  5. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment.
  6. BRAF/MEK inhibitors within 2 weeks prior to the first dose of study treatment.
  7. Systemic radiation therapy within 4 weeks, prior focal radiotherapy within 2 weeks, or radiopharmaceuticals (strontium, samarium) within 8 weeks prior to the first dose of study treatment.
  8. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment.
  9. Other prior malignancy, except for adequately treated basal or squamous cell skin cancer or in situ cancers; or any other cancer from which the patient has been disease-free for at least 3 years.
  10. Active, untreated central nervous system metastases.
  11. Active autoimmune disease or a documented history of autoimmune disease
  12. Active diverticulitis.
  13. Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  14. Significant cardiovascular disease

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Varlilumab and Nivolumab
Drug: Combination of varlilumab and nivolumab

Phase I: Varlilumab dosing will be dependent on the cohort assigned in combination with 3 mg/kg of nivolumab every two weeks.

Phase II: Patients with CRC, RCC or GBM enrolled in Phase ll will receive 3.0 mg/kg of varlilumab in combination with 240 mg of nivolumab every 2 weeks. Patients with SCCHN or ovarian cancer will receive varlilumab at a dose of either 3 mg/kg every 2 weeks, 3 mg/kg every 12 weeks, or 0.3 mg/kg every 4 weeks, in combination with 240 mg of nivolumab every 2 weeks.

Patients may be discontinued from receiving study treatment based on the results of disease assessments or if experiencing intolerable side effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase I: Number of participants with treatment-related adverse events as determined by CTCAE v4.0, dose-limiting toxicities, and laboratory abnormalities.
Time Frame: Safety follow-up is 100 days from last study drug dose.
Safety follow-up is 100 days from last study drug dose.
Phase II: Preliminary antitumor activity of the combination of varlilumab and nivolumab as measured by objective response rate (ORR) in patients with CRC, ovarian cancer, RCC and SCCHN and Overall Survival-12 months in GBM.
Time Frame: Evaluated every 8 weeks following treatment initiation until treatment is discontinued or disease progression, for up to 3 years.
Evaluated every 8 weeks following treatment initiation until treatment is discontinued or disease progression, for up to 3 years.

Collaborators and Investigators

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

Sponsor

Celldex Therapeutics

Collaborators

Bristol-Myers Squibb

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

January 1, 2015

Primary Completion (Actual)

December 12, 2018

Study Completion (Actual)

December 12, 2018

Study Registration Dates

First Submitted

December 18, 2014

First Submitted That Met QC Criteria

January 7, 2015

First Posted (Estimate)

January 12, 2015

Study Record Updates

Last Update Posted (Actual)

December 9, 2019

Last Update Submitted That Met QC Criteria

December 5, 2019

Last Verified

November 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDX1127-02

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.

Clinical Trials on Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Clinical Trials on Combination of varlilumab and nivolumab

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Panama

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe