Addition of SNS-301 to Checkpoint Inhibitor Treatment in Metastatic/Recurrent SCCHN

To evaluate safety, immunogenicity and anti-tumor responses of intradermally delivered SNS-301 added to checkpoint inhibitor therapy in locally advanced unresectable or metastatic/recurrent squamous cell carcinoma of the head and neck (SCCHN) patients.

This is a Phase 1/2, open-label, multi-center trial to evaluate the safety, immunogenicity and preliminary clinical efficacy of SNS-301 delivered intradermally in addition to pembrolizumab in patients with locally advanced unresectable or metastatic/recurrent SCCHN. The trial population consists of patients with locally advanced unresectable or metastatic/recurrent SCCHN who are currently receiving checkpoint inhibitor (CPI) therapy (Cohort A) or are naïve to CPI therapy (Cohort B). Patients who are currently receiving CPI therapy must have a best response of stable disease (SD) or first evidence of progressive disease (PD) after a minimum of 12 weeks of treatment with a CPI. Patients receiving a CPI other than pembrolizumab will be switched over to pembrolizumab at the time of entering this study. Patients receiving pembrolizumab in the first line setting must be PD-L1 positive.

Eligibility Criteria:
Inclusion Criteria:

1. Signed informed consent.
2. Be 18 years of age or older.
3. Have histologically or cytologically documented locally advanced unresectable or metastatic/recurrent SCCHN and meet the criteria of either Cohort A or B.

   Cohort A: Patients with Ongoing CPI Therapy
   1. Patients currently receiving a checkpoint inhibitor (CPI: anti-PD-1 and anti-PD-L1 agents).
   2. Patients currently receiving a CPI must be considered by Investigator to have the potential to derive clinical benefit from continued treatment with pembrolizumab.
   3. Based on RECIST 1.1/iRECIST criteria on current CPI treatment (prior to initiation of this study), patients must have a best response of stable disease (SD) or first evidence of progressive disease (PD) after a minimum of 12 weeks of a CPI.
   4. Patients on other CPI therapy than pembrolizumab must be willing to switch over to pembrolizumab therapy.

   Cohort B: Patients without Previous CPI Therapy
   1. Patients must be checkpoint inhibitor naïve (anti-PD-1 and anti-PD-L1 agents)
   2. Patients should receive study treatment as first line (PD-L1 positive) or as second line (PD-L1 negative) systemic therapy in the advanced/metastatic setting.
4. Have measurable disease by RECIST 1.1.
5. Eastern Cooperative Oncology Group (ECOG) Performance Scale 0-1.
6. Have a life expectancy of ≥ 3 months.
7. Be willing to provide a pre-treatment tissue sample (archived or fresh).
8. Demonstrate adequate organ function: hematological, renal, hepatic, coagulation parameters.
9. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two highly effective contraceptive methods during the treatment period and for at least 180 days after the last dose of study treatment. For male patients: Agree that during the period specified above, men will not father a child. Male patients must remain abstinent, must be surgically sterile during the treatment period and for at least 180 days after the last dose of study treatment.

Exclusion Criteria:

1. Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 0.
2. Participated on a clinical trial of an investigational agent and/or investigational device within 28 days prior to Day 0.
3. Uncontrolled tumor-related pain.
4. Malignancies other than indications open for enrollment within 3 years prior to Day 0.
5. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
6. Known hypersensitivity allergy or contraindication to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the PD-1/PD-L1 inhibitor formulation.
7. Active autoimmune disease that has required systemic treatment in the past 2 years
8. History or any evidence of interstitial lung disease.
9. History of HIV. HIV antibody testing recommended per investigator's clinical suspicion.
10. Active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C (HCV qualitative RNA detected); testing recommended per investigator's clinical suspicion.
11. Severe infections within 4 weeks prior to enrollment.
12. Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 0.
13. History or current evidence of any condition, therapy or laboratory abnormality that in the opinion of the treating investigator might confound the results of the trial.
14. Prior allogeneic stem cell or solid organ transplant.
15. Known previous or ongoing, active psychiatric or substance abuse disorders that would interfere with the requirements of the trial.
16. Treatment with systemic immunomodulating agents (including but not limited to IFNs, IL-2, ipilimumab) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to first dose.
17. Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study.