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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

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ClinicalTrials.gov Identifier: NCT02335918
Recruitment Status : Completed
First Posted : January 12, 2015
Last Update Posted : December 9, 2019
Bristol-Myers Squibb
Information provided by (Responsible Party):
Celldex Therapeutics

Brief Summary:
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 or disease Intervention/treatment Phase
Squamous Cell Carcinoma of the Head and Neck (SCCHN) Ovarian Carcinoma-Enrollment Completed Colorectal Cancer (CRC)-Enrollment Completed Renal Cell Carcinoma (RCC) (Phase ll Only) Glioblastoma (GBM) (Phase ll Only)-Enrollment Completed Drug: Combination of varlilumab and nivolumab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 175 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
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
Study Start Date : January 2015
Actual Primary Completion Date : December 12, 2018
Actual Study Completion Date : December 12, 2018

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.

Primary Outcome Measures :
  1. 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. ]
  2. 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. ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02335918

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Sponsors and Collaborators
Celldex Therapeutics
Bristol-Myers Squibb
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Celldex Therapeutics
ClinicalTrials.gov Identifier: NCT02335918    
Other Study ID Numbers: CDX1127-02
First Posted: January 12, 2015    Key Record Dates
Last Update Posted: December 9, 2019
Last Verified: November 2018
Keywords provided by Celldex Therapeutics:
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Squamous Cell Carcinoma of Head and Neck
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Carcinoma, Squamous Cell
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Head and Neck Neoplasms
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action