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.
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.
