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Squamous Cell Carcinoma of the Head and Neck (SCCHN)Phase 1/2NCT02335918

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

A Phase 1/2 study testing Combination of varlilumab and nivolumab in people with Squamous Cell Carcinoma of the Head and Neck (SCCHN) and Ovarian Carcinoma-Enrollment Completed, run by Celldex Therapeutics at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Combination of varlilumab and nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
175 participants
Where
19 sitesUnited States
Study dates
Jan 2015to 12 Dec 2018
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.
  • 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).
  • Measurable (target) disease.
  • Life expectancy ≥ 12 weeks.
  • 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.

Who cannot join

  • History of severe hypersensitivity reactions to other monoclonal antibodies.
  • Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 antibody.
  • Receipt of anti-CTLA-4 or anti-CD27 antibody within 3 months prior to the planned start of study treatment.
  • Use of any monoclonal based therapies within 2-4 weeks prior to the first dose of study treatment.
  • Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to the planned start of study treatment.
  • BRAF/MEK inhibitors within 2 weeks prior to the first dose of study treatment.
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  • 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.
  • Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within 2 weeks prior to first dose of study treatment.
  • 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.
  • Active, untreated central nervous system metastases.
  • Active autoimmune disease or a documented history of autoimmune disease
  • Active diverticulitis.
  • Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity.
  • Significant cardiovascular disease

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • University of Colorado Medical Center

    Aurora, Colorado, 80045

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Inova Schar Cancer Institute Research

    Fairfax, Virginia, 22031

  • Parkview Research Center

    Fort Wayne, Indiana, 46845

  • Northwest Georgia Oncology Centers PC

    Marietta, Georgia, 30060

  • Mount Sinai Medical Center

    Miami Beach, Florida, 33140

  • Smilow Cancer Hospital at Yale University Cancer Center

    New Haven, Connecticut, 06519

  • Laura and Isaac Perlmutter Cancer Center

    New York, New York, 10016

  • Columbia University Medical Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • The Stanford Center for Clinical and Translational Education and Research

    Palo Alto, California, 94304

  • Providence Health & Services

    Portland, Oregon, 97213

  • UCSF Helen Diller Family Comprehensive Cancer Center

    San Francisco, California, 94115

  • University of Arizona Cancer Center

    Tucson, Arizona, 85719

  • Georgetown University

    Washington D.C., District of Columbia, 20007

  • George Washington University School of Medicine and Health Sciences

    Washington D.C., District of Columbia, 20037

  • Wake Forest Baptist Health

    Winston-Salem, North Carolina, 27157

Other trials in United States

About this study

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

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.

Read the 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.

Being tested
Combination of varlilumab and nivolumab
Keywords
Opdivo®
Medical subject headings
Squamous Cell Carcinoma of Head and Neck, Colorectal Neoplasms, Carcinoma, Renal Cell, Glioblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Combination of varlilumab and nivolumabDrug

    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.

Study groups in NCT02335918
Study groupRoleWhat they receive
Varlilumab and NivolumabExperimentalNot described
Receives: Drug: Combination of varlilumab and nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Number of participants with treatment-related adverse events as determined by CTCAE v4.0, dose-limiting toxicities, and laboratory abnormalities.

    Measured: 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.

    Measured: Evaluated every 8 weeks following treatment initiation until treatment is discontinued or disease progression, for up to 3 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jan 2015 (estimated)
  2. Study startJan 2015
  3. Primary completion12 Dec 2018
  4. Study completion12 Dec 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
175 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02335918
Sponsor's protocol ID
CDX1127-02
Status last verified
Nov 2018
First submitted
18 Dec 2014
Last updated
9 Dec 2019
Results posted
No
Data monitoring committee
No

Publications

  • Sanborn RE, Pishvaian MJ, Callahan MK, Weise A, Sikic BI, Rahma O, Cho DC, Rizvi NA, Sznol M, Lutzky J, Bauman JE, Bitting RL, Starodub A, Jimeno A, Reardon DA, Kaley T, Iwamoto F, Baehring JM, Subramaniam DS, Aragon-Ching JB, Hawthorne TR, Rawls T, Yellin M, Keler T. Safety, tolerability and efficacy of agonist anti-CD27 antibody (varlilumab) administered in combination with anti-PD-1 (nivolumab) in advanced solid tumors. J Immunother Cancer. 2022 Aug;10(8):e005147. doi: 10.1136/jitc-2022-005147.

    PubMed 35940825

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Combination of varlilumab and nivolumab in people with Squamous Cell Carcinoma of the Head and Neck (SCCHN) and Ovarian Carcinoma-Enrollment Completed, run by Celldex Therapeutics at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02335918, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2019.

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