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

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

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.

Study Overview

• Status: Terminated
• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Intervention / Treatment: Drug: SNS-301; Drug: Pembrolizumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California - San Francisco
  • Delaware
    • Newark, Delaware, United States, 19713
      • Christiana Care
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Alliance for Multispeciality Research
  • New York
    • New York, New York, United States, 10029
      • Mt. Sinai
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • New Orleans Clinical Research
  • Texas
    • Webster, Texas, United States, 77598
      • Clear Lake Specialties
  • Wisconsin
    • Madison, Wisconsin, United States, 53715
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: SNS-301 added to pembrolizumab; SNS-301; Pembrolizumab

Drug: SNS-301; 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.; Drug: Pembrolizumab; 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.; Other Names: Keytruda

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Related Expression	Determine immune expression pretreatment, changes during treatment and at progression	12 weeks
Tumor Specific Oncoproteins	Determine expression pretreatment, during treatment and at progression	12 weeks
ASPH Expression	Determine pretreatment expression, changes during treatment and at progression	12 weeks
Cytokine/Chemokine Profiling	Determine cytokine/chemokine profile pretreatment, changes during treatment and at progression	12 weeks
ctDNA	Determine ctDNA profile pretreatment, changes during treatment and at progression	12 weeks

Collaborators and Investigators

• Sponsor: Sensei Biotherapeutics, Inc.
• Investigators: Study Director: Ramzi Melhem, MD, Sensei Biotherapeutics

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2019
• Primary Completion (Actual): June 28, 2021
• Study Completion (Actual): June 28, 2021

Study Registration Dates

• First Submitted: July 16, 2019
• First Submitted That Met QC Criteria: July 23, 2019
• First Posted (Actual): July 26, 2019

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 23, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: SNS-301-2-2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underline the results reported in the article, after deidentification (text, tables, figures and appendices) will be shared to researchers who have provide a methodologically sound proposal and sign a data access agreement.
• IPD Sharing Time Frame: Beginning 9 months and ending 36 months following article publication.
• IPD Sharing Access Criteria: Access will be considered to researchers who provide a methodologically sound proposal. Analysis must achieve the aims outlined in the approved proposal Proposals should be directed to info@senseibio.com. To gain access, data requestors will need to sign a data access agreement. Data are available for 36 months following article publication.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No