Squamous Cell Carcinoma
Conditions
Brief summary
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.
Interventions
DRUGBavituximab
Bavituximab is a chimeric (human/mouse) monoclonal antibody (mAb) derived from murine mAb 3G4 that targets phosphatidylserine (PS) after binding to β2-glycoprotein 1 (β2-GP1).
DRUGPembrolizumab
Pembrolizumab is a highly selective humanized mAb designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Sponsors
University of Maryland, Baltimore
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Pembro and Bavituximab for progressive recurrent/metastatic squamous cell carcinoma of head and neck
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CR+PR | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 55 months. | overall response rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 55 months. | Progression free survival |
| Disease Progression | From date of randomization until the date of first documented progression up to 100 weeks | Number of participants with disease progression. For duration of response, CT imaging and RECIST criteria were reviewed to measure patient's response and time of that duration. One cycle is 21 days. |
| Survival | From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 55 months. | Overall survival |
| Participants With Laboratory Correlates of Response | through study completion, an average of 1 year | Number of participants with laboratory correlates of response. The following outcomes are being measured: 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. These outcome measures are determined through archival tumor tissue and next generation sequencing. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab + Bavituximab Pembro and Bavituximab for progressive recurrent/metastatic squamous cell carcinoma of head and neck
Bavituximab: Bavituximab is a chimeric (human/mouse) monoclonal antibody (mAb) derived from murine mAb 3G4 that targets phosphatidylserine (PS) after binding to β2-glycoprotein 1 (β2-GP1).
Pembrolizumab: Pembrolizumab is a highly selective humanized mAb designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Pembrolizumab + Bavituximab |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 67 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 6 / 7 |
| other Total, other adverse events | 6 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
CR+PR
overall response rate
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 55 months.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pembrolizumab + Bavituximab | CR+PR | Progressive Disease | 7 Participants |
| Pembrolizumab + Bavituximab | CR+PR | Complete Response | 0 Participants |
Secondary
Disease Progression
Number of participants with disease progression. For duration of response, CT imaging and RECIST criteria were reviewed to measure patient's response and time of that duration. One cycle is 21 days.
Time frame: From date of randomization until the date of first documented progression up to 100 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pembrolizumab + Bavituximab | Disease Progression | Progression prior to Cycle 2 | 1 Participants |
| Pembrolizumab + Bavituximab | Disease Progression | Progression at Cycle 2 | 2 Participants |
| Pembrolizumab + Bavituximab | Disease Progression | Progression at Cycle 3 | 3 Participants |
| Pembrolizumab + Bavituximab | Disease Progression | Progression at Cycle 4 | 1 Participants |
Secondary
Participants With Laboratory Correlates of Response
Number of participants with laboratory correlates of response. The following outcomes are being measured: 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. These outcome measures are determined through archival tumor tissue and next generation sequencing.
Time frame: through study completion, an average of 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pembrolizumab + Bavituximab | Participants With Laboratory Correlates of Response | Laboratory correlates of response | 0 Participants |
| Pembrolizumab + Bavituximab | Participants With Laboratory Correlates of Response | No Laboratory correlates of response | 7 Participants |
Secondary
Progression
Progression free survival
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 55 months.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pembrolizumab + Bavituximab | Progression | Progressive Disease | 7 Participants |
| Pembrolizumab + Bavituximab | Progression | Progression Free Survival | 0 Participants |
Secondary
Survival
Overall survival
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 55 months.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Pembrolizumab + Bavituximab | Survival | Patient Expired | 6 Participants |
| Pembrolizumab + Bavituximab | Survival | Outcome Unknown | 1 Participants |