1922GCCC: Pembro and Bavituximab for Squamous Cell Carcinoma of Head and Neck
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|ClinicalTrials.gov Identifier: NCT04150900|
Recruitment Status : Recruiting
First Posted : November 5, 2019
Last Update Posted : March 22, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Squamous Cell Carcinoma||Drug: Bavituximab Drug: Pembrolizumab||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||29 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Pembro and Bavituximab for progressive recurrent/metastatic squamous cell carcinoma of head and neck|
|Masking:||None (Open Label)|
|Official Title:||1922GCCC: PHASE 2 STUDY OF PEMBROLIZUMAB AND BAVITUXIMAB FOR PROGRESSIVE RECURRENT/METASTATIC SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK|
|Actual Study Start Date :||January 13, 2020|
|Estimated Primary Completion Date :||January 1, 2025|
|Estimated Study Completion Date :||January 1, 2027|
Experimental: Pembrolizumab + Bavituximab
Pembro and Bavituximab for progressive recurrent/metastatic squamous cell carcinoma of head and neck
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 is a highly selective humanized mAb designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
- 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 ]overall response rate
- 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 ]Progression free survival
- Time [ Time Frame: From date of randomization until the date of first documented progression up to 100 weeks ]Duration of response
- Survival [ Time Frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months ]Overall survival
- Number of participants with laboratory correlates of resposne [ Time Frame: through study completion, an average of 1 year ]
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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
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): NCT04150900
|Contact: Ranee Mehra, MDemail@example.com|
|Contact: Joann Alimurongfirstname.lastname@example.org|
|United States, Maryland|
|University of Maryland Medical Center||Recruiting|
|Baltimore, Maryland, United States, 21201|
|Contact: Ranee Mehra, MD 410-328-4059 email@example.com|
|Contact: Joann Alimurong 410-328-2703 firstname.lastname@example.org|
|Responsible Party:||University of Maryland, Baltimore|
|Other Study ID Numbers:||
|First Posted:||November 5, 2019 Key Record Dates|
|Last Update Posted:||March 22, 2023|
|Last Verified:||March 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Carcinoma, Squamous Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Squamous Cell
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action