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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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An Open-Label, Multi-Center Trial of SNS-301 Added to Pembrolizumab in Patients With Locally Advanced Unresectable or Metastatic/Recurrent Squamous Cell Carcinoma of the Head and Neck

Conditions
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Squamous Cell Carcinoma of the Head and Neck

Intervention / Treatment
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* Drug: SNS-301
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent. Be 18 years of age or older. 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 Patients currently receiving a checkpoint inhibitor (CPI: anti-PD-1 and anti-PD-L1 agents). Patients currently receiving a CPI must be considered by Investigator to have the potential to derive clinical benefit from continued treatment with pembrolizumab. 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. Patients on other CPI therapy than pembrolizumab must be willing to switch over to pembrolizumab therapy. Cohort B: Patients without Previous CPI Therapy Patients must be checkpoint inhibitor naïve (anti-PD-1 and anti-PD-L1 agents) 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. Have measurable disease by RECIST 1.1. Eastern Cooperative Oncology Group (ECOG) Performance Scale 0-1. Have a life expectancy of ≥ 3 months. Be willing to provide a pre-treatment tissue sample (archived or fresh). Demonstrate adequate organ function: hematological, renal, hepatic, coagulation parameters. 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: Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day 0. Participated on a clinical trial of an investigational agent and/or investigational device within 28 days prior to Day 0. Uncontrolled tumor-related pain. Malignancies other than indications open for enrollment within 3 years prior to Day 0. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins. Known hypersensitivity allergy or contraindication to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the PD-1/PD-L1 inhibitor formulation. Active autoimmune disease that has required systemic treatment in the past 2 years History or any evidence of interstitial lung disease. History of HIV. HIV antibody testing recommended per investigator's clinical suspicion. Active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C (HCV qualitative RNA detected); testing recommended per investigator's clinical suspicion. Severe infections within 4 weeks prior to enrollment. Received therapeutic oral or IV antibiotics within 2 weeks prior to Day 0. 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. Prior allogeneic stem cell or solid organ transplant. Known previous or ongoing, active psychiatric or substance abuse disorders that would interfere with the requirements of the trial. 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SNS-301 added to pembrolizumab<br>SNS-301 Pembrolizumab | Drug: SNS-301<br>* Day 0, Week 3, Week 6, Week 9 then every 6 weeks (±3 days) for 6 additional doses, thereafter every 12 weeks (±3 days) up to 24 months.<br>Drug: Pembrolizumab<br>* Pembrolizumab (200 mg dose) IV infusion will be administered over 30 minutes every 3 weeks up to 24 months or Pembrolizumab (400 mg dose) IV will be administered over 30 minutes every 6 weeks up to 24 months.<br>* Other names: Keytruda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events of SNS-301 in Addition to Pembrolizumab | Number of adverse events including adverse events of special interest as assessed by CTCAE v5.0 | 12 weeks | 
| Objective Response Rate by RECIST and iRECIST | Objective response rate based on best objective response during the study. Objective tumor response definitions included: Complete response (CR): Disappearance of all target lesions, Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters, Progressive disease (PD): At least a 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm and Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum on study. | 12 weeks | 
| Duration of Response by RECIST 1.1 and iRECIST | Duration of response calculated from date of first response to date of progression. Objective tumor response definitions included: Complete response (CR): Disappearance of all target lesions, Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters, Progressive disease (PD): At least a 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm and Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum on study. | 12 weeks | 
| Disease Control Rate by RECIST 1.1 and iRECIST | Disease control rate calculated as the proportion of patients with stable disease or better. Objective tumor response definitions included: Complete response (CR): Disappearance of all target lesions, Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters, Progressive disease (PD): At least a 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm and Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum on study. | 12 weeks | 
| Progression Free Survival by RECIST 1.1 and iRECIST | Progression free survival calculated from the date of start of treatment to date of progression. Objective tumor response definitions included: Complete response (CR): Disappearance of all target lesions, Partial response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters, Progressive disease (PD): At least a 20% increase in the sum of diameters of the target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm and Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum on study. | 12 weeks | 
| Overall Survival | Overall survival calculated from date of treatment to date of death. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antigen-specific Response | Measure levels at pretreatment, changes during treatment and at progression or end of study | 12 weeks | 
| TCR Sequencing | Determine TCR diversity pretreatment, changes during treatment and at progression or end of study | 12 weeks | 
| Immune Gene Transcript Profiling | Determine gene signature pretreatment, during treatment and at progression | 12 weeks | 
| Profiling of Pro-inflammatory/Immunosuppressive Molecules | Measure levels at pretreatment, changes during treatment and at progression or end of study | 12 weeks |