Lack of Eligible subjects at study site

This is an Early Feasibility Study (EFS) investigating the use of the Hemopurifier to clear immunosuppressive exosomes in combination with pembrolizumab (Keytruda) in the front line setting, in patients with advanced and/or metastatic squamous cell carcinoma of the head and neck.

All 12 patients enrolled into this Early Feasibility Phase I clinical trial will receive the same treatment of Hemopurifier plus Pembrolizumab (i.e., 2 rounds of Hemopurifier plus Pembrolizumab followed by Pembrolizumab only up to 2 years). Prior to initiation of the Hemopurifier treatment on Day 1, each subject will undergo phlebotomy to provide a baseline EDTA anti-coagulated blood sample, 30ml (< 3 tablespoons of blood) for the assessments of total exosome protein (TEP) levels and exosome profiles. The kinetics of exosome depletion will be evaluated in the study participants using serial blood samples (5ml) collected hourly during the 4h-depletion period by the Hemopurifier on Day 1. In addition, to evaluate kinetics of exosome recovery, 30ml of blood will be collected just prior to Pembrolizumab infusion (day 1) and on days 7 and 14 after Hemopurifier plus Pembrolizumab treatment during cycle 1 and 2. Exosome recovery after Hemopurifier + Pembrolizumab therapy will be evaluated and used to determine the rate of TEP recovery for each patient. Serial monitoring of TEP during Hemopurifier treatment (hourly during the 4h-depletion period), before Pembrolizumab infusion and after the second round of Pembrolizumab (days 7, and 14) will be done as for the first treatment. Only 2 Hemopurifier treatments will be given. For third and later rounds of Pembrolizumab, the investigators will continue to draw 30mL blood prior to Pembrolizumab infusion for the assessments of TEP levels and exosome profiles.

Inclusion Criteria:

1. Recurrent or metastatic HNSCC (oral cavity, oropharynx, larynx, hypopharynx) and not amenable to local therapy with curative intent (surgery or radiation therapy)

2. Qualifies for Pembrolizumab monotherapy as part of standard of care (has PD-L1 CPS ≥1)

3. ECOG performance status of 0-1

4. Measurable disease by RECIST 1.1

5. Be > 18 years of age on day of signing informed consent

6. Be willing and able to provide written informed consent for the trial

7. Life expectancy of at least 12 weeks based on investigator estimate

8. Adequate organ function as defined as:

   • WBC ≥ 2000/μL
   • Neutrophils ≥ 1500/μL
   • Platelets ≥ 100 x103/μL
   • Hemoglobin ≥ 8.0 g/dL
   • serum creatinine < 1.5 x ULN or creatinine clearance (CrCl) > 40 mL/min (using the Cockcroft-Gault formula)
   • AST/ALT < 3 x ULN
   • Total bilirubin < 1.5 x ULN (except subjects with Gilbert Syndrome who can have total bilirubin < 3mg/dL.

9. Women of childbearing potential (WCBP) must have a negative urine pregnancy test within 7 days prior to the first study intervention.

10. WCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and through 120 days after the last dose of study treatment. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation.

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Exclusion Criteria:

1. Patients with salivary gland SCC or cutaneous SCC will be excluded

2. Has received systemic therapy (chemotherapy, immunotherapy, investigational therapy) for the treatment of recurrent/metastatic disease. Systemic therapy given concurrent with radiation treatment in the recurrent setting does not exclude the patient.

3. Untreated brain metastasis or leptomeningeal metastasis.

4. Tumor invades into the internal carotid artery or other major blood vessels whereby the treating investigator feels anti-coagulation is contraindicated.

5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (Prednisone > 10mg or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.

6. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic therapy or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.

7. Has a history of non-infectious pneumonitis that required steroids, evidence of interstitial lung disease, or currently active non-infectious pneumonitis.

8. Has an active infection requiring systemic therapy.

9. 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.

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

11. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) in the recurrent/metastatic setting. Patients that received any of these agents in the upfront curative intent setting can be enrolled as long as it has been 1 year since the last dose.

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

13. Has known active Hepatitis B or active Hepatitis C

14. Has received a live vaccine within 30 days prior to the first dose of trial treatment.

15. Concurrent therapy with an angiotensin-converting enzyme (ACE) inhibitor. ACE inhibitors must be discontinued at least 14 days prior to initiation of each Hemopurifier treatment and remain discontinued for 24 hours post treatment.

16. Systolic blood pressure less than 100 on at least 2 readings

17. Subjects with electro-cardiograms (ECG) showing clinically significant abnormalities.

18. Recent history of bleeding or bleeding disorders or any condition whereby in the opinion of the treating investigator giving anti-coagulation during the Hemopurifier treatment would be contraindicated

19. Any disorder or condition that in the opinion of the treating investigator would not be able to tolerate dialysis catheter placement, blood volume losses during Hemopurifier treatment or research blood draws.

20. History of heparin allergy or heparin induced thrombocytopenia.

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