Clinical Trials /

1922GCCC: Pembro and Bavituximab for Squamous Cell Carcinoma of Head and Neck

NCT04150900

Description:

This phase II single arm study is being done to determine if bavituximab could potentially synergize with PD-1 inhibitor therapy to generate an effective anti-tumor immune response in patients with recurrent/metastatic squamous cell head and neck cancer (HNSCC) who progressed on a PD-1 inhibitor.

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 1922GCCC: Pembro and Bavituximab for Squamous Cell Carcinoma of Head and Neck
  • Official Title: 1922GCCC: PHASE 2 STUDY OF PEMBROLIZUMAB AND BAVITUXIMAB FOR PROGRESSIVE RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

Clinical Trial IDs

  • ORG STUDY ID: 1922GCCC
  • NCT ID: NCT04150900

Conditions

  • Squamous Cell Carcinoma

Interventions

DrugSynonymsArms
BavituximabPembrolizumab + Bavituximab
PembrolizumabPembrolizumab + Bavituximab

Purpose

This phase II single arm study is being done to determine if bavituximab could potentially synergize with PD-1 inhibitor therapy to generate an effective anti-tumor immune response in patients with recurrent/metastatic squamous cell head and neck cancer (HNSCC) who progressed on a PD-1 inhibitor.

Detailed Description

      The goal of this study is to assess whether treatment with bavituximab shifts the cellular
      balance to favor an effective T-cell mediated antitumor response resulting to an enhanced
      response in conjunction with pembrolizumab. Bavituximab is a chimeric (human/mouse)
      monoclonal antibody that targets phosphatidylserine (PS). PS facilitates the recognition and
      clearance of dying cells, triggering the release of immunosuppressive cytokines and
      inhibiting the production of proinflammatory cytokines. Within the tumor microenvironment, PS
      polarizes macrophages toward an immunosuppressive phenotype. Bavituximab upregulates the
      adaptive T cell-mediated response through crosslinking FCRγ and dampening of signaling
      between PS and PS receptors on immunosuppressive myeloid-derived suppressor cells.

      Thus, the investigators are doing this phase II single arm study to determine if bavituximab
      could potentially synergize with PD-1 inhibitor therapy to generate an effective anti-tumor
      immune response in patients with recurrent/metastatic squamous cell head and neck cancer
      (HNSCC) who progressed on a PD-1 inhibitor.
    

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + BavituximabExperimentalPembro and Bavituximab for progressive recurrent/metastatic squamous cell carcinoma of head and neck
  • Bavituximab
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Patients will have recurrent/metastatic head and neck cancer and will have
             radiographic evidence of progression on prior immune checkpoint inhibitor therapy,
             including nivolumab, pembrolizumab, durvalumab and atezolizumab. Patients must have
             progressed on prior platinum therapy either in the recurrent setting or within 6
             months of treatment with cisplatin and radiation in the potentially curative setting.

          -  Be willing and able to provide written informed consent/assent for the trial.

          -  Be > or equal to 18 years of age on day of signing informed consent.

          -  Have measurable disease based on RECIST 1.1.

          -  Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
             prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples
             cannot be provided (e.g. inaccessible or subject safety concern) may submit an
             archived specimen only upon agreement from the PI.

          -  Have a performance status of 0 or 1 on the ECOG Performance Scale.

          -  Demonstrate adequate organ function as defined in Table 1, all screening labs should
             be performed within 10 days of treatment initiation.

          -  Female subject of childbearing potential must have a negative urine or serum pregnancy
             within 72 hours prior to receiving the first dose of study medication. If the urine
             test is positive or cannot be confirmed as negative, a serum pregnancy test will be
             required.

          -  Female subjects of childbearing potential (Section 6.2) must be willing to use an
             adequate method of contraception as outlined in Section 6.2 - Contraception, for the
             course of the study through 120 days after the last dose of study medication.

        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
        for the subject.

        -Male subjects of childbearing potential (Section 6.2) must agree to use an adequate method
        of contraception as outlined in Section 6.2- Contraception, starting with the first dose of
        study therapy through 120 days after the last dose of study therapy.

        Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
        for the subject.

        Exclusion Criteria:

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigational
             device within 4 weeks of the first dose of treatment.

          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial
             treatment.

          -  Has a known history of active TB (Bacillus Tuberculosis).

          -  Hypersensitivity to pembrolizumab or any of its excipients. History of
             hypersensitivity to other antibodies can be discussed with the PI to determine
             eligibility.

          -  Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
             Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events
             due to agents administered more than 4 weeks earlier.

          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
             baseline) from adverse events due to a previously administered agent.

        Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify
        for the study.

        Note: If subject received major surgery, they must have recovered adequately from the
        toxicity and/or complications from the intervention prior to starting therapy.

          -  Has experienced an immune-related adverse event requiring discontinuation of a prior
             checkpoint inhibitor.

          -  Has a known additional malignancy that is progressing or requires active treatment.
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
             skin that has undergone potentially curative therapy or in situ cervical cancer.

          -  Has known active central nervous system (CNS) metastases and/or carcinomatous
             meningitis. Subjects with previously treated brain metastases may participate provided
             they are stable (without evidence of progression by imaging for at least four weeks
             prior to the first dose of trial treatment and any neurologic symptoms have returned
             to baseline), have no evidence of new or enlarging brain metastases, and are not using
             steroids for at least 7 days prior to trial treatment. This exception does not include
             carcinomatous meningitis which is excluded regardless of clinical stability.

          -  Has active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
             replacement (such as prednisone 10mg daily or its equivalent) for adrenal or pituitary
             insufficiency, etc.) is not considered a form of systemic treatment.

          -  Has known history of, or any evidence of active, non-infectious pneumonitis.

          -  Has an active infection requiring systemic therapy.

          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality
             that might confound the results of the trial, interfere with the subject's
             participation for the full duration of the trial, or is not in the best interest of
             the subject to participate, in the opinion of the treating investigator.

          -  Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment.

          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
             [qualitative] is detected).

          -  Has received a live vaccine within 30 days of planned start of study therapy. Note:
             Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
             are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
             attenuated vaccines, and are not allowed.

        Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg
        daily prednisone equivalent) or other immunosuppressive medications within 14 days of
        randomization. Inhaled or topical steroids and adrenal replacement steroid doses < 10 mg
        daily prednisone equivalent, are permitted in the absence of active autoimmune disease.

        Inclusion of Women and Minorities

        Both men and women of all races and ethnic groups are eligible for this trial.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:CR+PR
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Safety Issue:
Description:overall response rate

Secondary Outcome Measures

Measure:Progression
Time Frame:From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
Safety Issue:
Description:Progression free survival
Measure:Time
Time Frame:From date of randomization until the date of first documented progression up to 100 weeks
Safety Issue:
Description:Duration of response
Measure:Survival
Time Frame:From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
Safety Issue:
Description:Overall survival
Measure:Number of participants with laboratory correlates of resposne
Time Frame:through study completion, an average of 1 year
Safety Issue:
Description:PD-L1 expression pre and post treatment Presence of TILs (tumor infiltrating lymphocytes) pre and post treatment Assessment of immune markers in pre-treatment fresh and post-treatment biopsies and blood. Assessment of genomics and tumor mutation burden in select patients.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Maryland, Baltimore

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