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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2017 by Celldex Therapeutics
Bristol-Myers Squibb
Information provided by (Responsible Party):
Celldex Therapeutics Identifier:
First received: December 18, 2014
Last updated: April 17, 2017
Last verified: April 2017
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.

Condition Intervention Phase
Squamous Cell Carcinoma of the Head and Neck (SCCHN)
Ovarian Carcinoma
Colorectal Cancer (CRC)
Renal Cell Carcinoma (RCC) (Phase ll Only)
Glioblastoma (GBM) (Phase ll Only)
Drug: Combination of varlilumab and nivolumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:

Further study details as provided by Celldex Therapeutics:

Primary Outcome Measures:
  • 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. ]
  • 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. ]

Estimated Enrollment: 205
Study Start Date: January 2015
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: April 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.


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

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 9 months of last dose of platinum therapy in the adjuvant, primary, recurrent or 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

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

    • 1d. Glioblastoma

    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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02335918

Contact: Celldex Therapeutics

United States, California
The Stanford Center for Clinical and Translational Education and Research Recruiting
Palo Alto, California, United States, 94304
Contact: Branimir Sikic, MD    650-725-6427   
Principal Investigator: Branimir Sikic, MD         
United States, Colorado
University of Colorado Medical Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Antonio Jimeno, MD    303-724-2478   
Principal Investigator: Antonio Jimeno, MD         
United States, Connecticut
Smilow Cancer Hospital at Yale University Cancer Center Recruiting
New Haven, Connecticut, United States, 06519
Contact: Matthew Madura    203-737-5381   
Contact: Amanda Ralabate, RN    203-752-7961   
Principal Investigator: Mario Sznol, MD         
United States, District of Columbia
Georgetown University Recruiting
Washington, DC, District of Columbia, United States, 20007
Contact: Laura Macke, RN   
Contact: Lisa Ley, RN   
Principal Investigator: Michael Pishvaian, MD         
United States, Florida
Mount Sinai Medical Center Recruiting
Miami Beach, Florida, United States, 33140
Contact: Jose Lutzky, MD   
Principal Investigator: Jose Lutzky, MD         
United States, Georgia
The Winship Cancer Institute, Emory University Withdrawn
Atlanta, Georgia, United States, 30322
United States, Indiana
Parkview Research Center Recruiting
Fort Wayne, Indiana, United States, 46845
Contact: Alexander Starodub, MD    260-373-8180   
Principal Investigator: Alexander Starodub, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Toni Choueiri, MD    617-632-4524   
Principal Investigator: Tony Choueiri, MD         
United States, Michigan
Barbara Ann Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Meghan Wyse, PhD   
Contact: Clarice Zuccaro   
Principal Investigator: Amy Weise, DO         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Fabio Iwamoto, MD    212-342-0571   
Principal Investigator: Fabio Iwamoto, MD         
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Margaret Callahan, MD, PhD    646-888-3359      
Principal Investigator: Margaret Callahan, MD, PhD         
United States, Oregon
Providence Health & Services Recruiting
Portland, Oregon, United States, 97213
Contact: Tara Foote, RN BSN OCN   
Contact: Kim Sutcliffe, RN   
Principal Investigator: Rachel Sanborn, MD         
United States, Virginia
Inova Schar Cancer Institute Research Recruiting
Fairfax, Virginia, United States, 22031
Contact: Jeanny Aragon-Ching, MD    202-741-2481   
Principal Investigator: Jeanny Aragon-Ching, MD         
Sponsors and Collaborators
Celldex Therapeutics
Bristol-Myers Squibb
  More Information

Responsible Party: Celldex Therapeutics Identifier: NCT02335918     History of Changes
Other Study ID Numbers: CDX1127-02
Study First Received: December 18, 2014
Last Updated: April 17, 2017

Keywords provided by Celldex Therapeutics:

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Colorectal Neoplasms
Carcinoma, Renal Cell
Head and Neck Neoplasms
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Kidney Neoplasms
Urologic Neoplasms processed this record on April 24, 2017