Squamous Cell Carcinoma of the Head and Neck
Conditions
Brief summary
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
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.
Interventions
DRUGSNS-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.
DRUGPembrolizumab
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.
Sponsors
Sensei Biotherapeutics, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open label
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival by RECIST 1.1 and iRECIST | 12 weeks | 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. |
| Objective Response Rate by RECIST and iRECIST | 12 weeks | 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. |
| Disease Control Rate by RECIST 1.1 and iRECIST | 12 weeks | 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. |
| Number of Participants With Adverse Events of SNS-301 in Addition to Pembrolizumab | 12 weeks | Number of adverse events including adverse events of special interest as assessed by CTCAE v5.0 |
| Duration of Response by RECIST 1.1 and iRECIST | 12 weeks | 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. |
| Overall Survival | 36 months | Overall survival calculated from date of treatment to date of death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immune Gene Transcript Profiling | 12 weeks | Determine gene signature pretreatment, during treatment and at progression |
| Antigen-specific Response | 12 weeks | Measure levels at pretreatment, changes during treatment and at progression or end of study |
| TCR Sequencing | 12 weeks | Determine TCR diversity pretreatment, changes during treatment and at progression or end of study |
| Profiling of Pro-inflammatory/Immunosuppressive Molecules | 12 weeks | Measure levels at pretreatment, changes during treatment and at progression or end of study |
Other
| Measure | Time frame | Description |
|---|---|---|
| Immune Related Expression | 12 weeks | Determine immune expression pretreatment, changes during treatment and at progression |
| ctDNA | 12 weeks | Determine ctDNA profile pretreatment, changes during treatment and at progression |
| Cytokine/Chemokine Profiling | 12 weeks | Determine cytokine/chemokine profile pretreatment, changes during treatment and at progression |
| ASPH Expression | 12 weeks | Determine pretreatment expression, changes during treatment and at progression |
| Tumor Specific Oncoproteins | 12 weeks | Determine expression pretreatment, during treatment and at progression |
Countries
United States
Participant flow
Pre-assignment details
Participants were required to provide archival biopsy material or have a fresh biopsy prior to dosing.
Participants by arm
| Arm | Count |
|---|---|
| SNS-301 Added to Pembrolizumab in Participants on a CPI >12 Weeks With a BOR SD/uPD * SNS-301
* Pembrolizumab
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.
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. | 21 |
| SNS-301 Added to Pembrolizumab in Participants CPI Naive/ First Line Systemic Therapy * SNS-301
* Pembrolizumab
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.
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. | 4 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 3 |
| Overall Study | Lack of Efficacy | 1 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Study termination by Sponsor | 18 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | SNS-301 Added to Pembrolizumab in Participants on a CPI >12 Weeks With a BOR SD/uPD | Total | SNS-301 Added to Pembrolizumab in Participants CPI Naive/ First Line Systemic Therapy |
|---|---|---|---|
| Age, Continuous | 62.6 years STANDARD_DEVIATION 7.42 | 61.1 years STANDARD_DEVIATION 8.92 | 53.3 years STANDARD_DEVIATION 13.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 21 Participants | 25 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 18 Participants | 2 Participants |
| Region of Enrollment United States | 21 Participants | 25 Participants | 4 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 1 Participants |
| Sex: Female, Male Male | 17 Participants | 20 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 21 | 0 / 4 |
| other Total, other adverse events | 16 / 21 | 2 / 4 |
| serious Total, serious adverse events | 5 / 21 | 1 / 4 |
Outcome results
Primary
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.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SNS-301 Added to Pembrolizumab in Participants on a CPI >12 Weeks With a BOR SD/uPD | Disease Control Rate by RECIST 1.1 and iRECIST | 9 participants |
| SNS-301 Added to Pembrolizumab in Participants CPI Naive/ First Line Systemic Therapy | Disease Control Rate by RECIST 1.1 and iRECIST | 1 participants |
Primary
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.
Time frame: 12 weeks
Population: A total of 18 patients were evaluable in patients who had previous pembrolizumab group and 1 patient was evaluable in the CPI naive group. One patient had a partial response with a DOR of 48.3 weeks. All other patients had stable disease or has progressive disease at the 12 week timeframe.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SNS-301 Added to Pembrolizumab in Participants on a CPI >12 Weeks With a BOR SD/uPD | Duration of Response by RECIST 1.1 and iRECIST | 48.3 weeks |
| SNS-301 Added to Pembrolizumab in Participants CPI Naive/ First Line Systemic Therapy | Duration of Response by RECIST 1.1 and iRECIST | 0 weeks |
Primary
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
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SNS-301 Added to Pembrolizumab in Participants on a CPI >12 Weeks With a BOR SD/uPD | Number of Participants With Adverse Events of SNS-301 in Addition to Pembrolizumab | 16 Participants |
| SNS-301 Added to Pembrolizumab in Participants CPI Naive/ First Line Systemic Therapy | Number of Participants With Adverse Events of SNS-301 in Addition to Pembrolizumab | 3 Participants |
Primary
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.
Time frame: 12 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| SNS-301 Added to Pembrolizumab in Participants on a CPI >12 Weeks With a BOR SD/uPD | Objective Response Rate by RECIST and iRECIST | Partial Response | 1 Participants |
| SNS-301 Added to Pembrolizumab in Participants on a CPI >12 Weeks With a BOR SD/uPD | Objective Response Rate by RECIST and iRECIST | Stable Disease | 8 Participants |
| SNS-301 Added to Pembrolizumab in Participants on a CPI >12 Weeks With a BOR SD/uPD | Objective Response Rate by RECIST and iRECIST | Progressive Disease | 9 Participants |
| SNS-301 Added to Pembrolizumab in Participants CPI Naive/ First Line Systemic Therapy | Objective Response Rate by RECIST and iRECIST | Partial Response | 0 Participants |
| SNS-301 Added to Pembrolizumab in Participants CPI Naive/ First Line Systemic Therapy | Objective Response Rate by RECIST and iRECIST | Stable Disease | 1 Participants |
| SNS-301 Added to Pembrolizumab in Participants CPI Naive/ First Line Systemic Therapy | Objective Response Rate by RECIST and iRECIST | Progressive Disease | 0 Participants |
Primary
Overall Survival
Overall survival calculated from date of treatment to date of death.
Time frame: 36 months
Population: Study stopped prematurely; no patients were assessed at 36 months thus no data collected. At the time of termination, four deaths occurred in the patients previously receiving pembrolizumab group and no deaths in the CPI naive group.
Primary
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.
Time frame: 12 weeks
Population: 19/25 patients were evaluable for this assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SNS-301 Added to Pembrolizumab in Participants on a CPI >12 Weeks With a BOR SD/uPD | Progression Free Survival by RECIST 1.1 and iRECIST | 9 Participants |
| SNS-301 Added to Pembrolizumab in Participants CPI Naive/ First Line Systemic Therapy | Progression Free Survival by RECIST 1.1 and iRECIST | 1 Participants |
Secondary
Antigen-specific Response
Measure levels at pretreatment, changes during treatment and at progression or end of study
Time frame: 12 weeks
Population: 16/25 patients were evaluable for this assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| SNS-301 Added to Pembrolizumab in Participants on a CPI >12 Weeks With a BOR SD/uPD | Antigen-specific Response | 0 ASPH antigen-specific responders |
| SNS-301 Added to Pembrolizumab in Participants CPI Naive/ First Line Systemic Therapy | Antigen-specific Response | 0 ASPH antigen-specific responders |
Secondary
Immune Gene Transcript Profiling
Determine gene signature pretreatment, during treatment and at progression
Time frame: 12 weeks
Population: Blood samples were collected. However, due to the lack of ASPH-specific T-cell responses in patients treated with SNS-301 and the subsequent discontinuation of the clinical trial, the samples were not analyzed and no data were generated.
Secondary
Profiling of Pro-inflammatory/Immunosuppressive Molecules
Measure levels at pretreatment, changes during treatment and at progression or end of study
Time frame: 12 weeks
Population: Blood samples were collected. However, due to the lack of ASPH-specific T-cell responses in patients treated with SNS-301 and the subsequent discontinuation of the clinical trial, the samples were not analyzed and no data were generated.
Secondary
TCR Sequencing
Determine TCR diversity pretreatment, changes during treatment and at progression or end of study
Time frame: 12 weeks
Population: Blood samples were collected. However, due to the lack of ASPH-specific T-cell responses in patients treated with SNS-301 and the subsequent discontinuation of the clinical trial, the samples were not analyzed and no data were generated.
Other Pre-specified
ASPH Expression
Determine pretreatment expression, changes during treatment and at progression
Time frame: 12 weeks
Population: Blood samples were collected. However, due to the lack of ASPH-specific T-cell responses in patients treated with SNS-301 and the subsequent discontinuation of the clinical trial, the samples were not analyzed and no data were generated.
Other Pre-specified
ctDNA
Determine ctDNA profile pretreatment, changes during treatment and at progression
Time frame: 12 weeks
Population: Blood samples were collected. However, due to the lack of ASPH-specific T-cell responses in patients treated with SNS-301 and the subsequent discontinuation of the clinical trial, the samples were not analyzed and no data were generated.
Other Pre-specified
Cytokine/Chemokine Profiling
Determine cytokine/chemokine profile pretreatment, changes during treatment and at progression
Time frame: 12 weeks
Population: Blood samples were collected. However, due to the lack of ASPH-specific T-cell responses in patients treated with SNS-301 and the subsequent discontinuation of the clinical trial, the samples were not analyzed and no data were generated.
Other Pre-specified
Immune Related Expression
Determine immune expression pretreatment, changes during treatment and at progression
Time frame: 12 weeks
Population: Blood samples were collected. However, due to the lack of ASPH-specific T-cell responses in patients treated with SNS-301 and the subsequent discontinuation of the clinical trial, the samples were not analyzed and no data were generated.
Other Pre-specified
Tumor Specific Oncoproteins
Determine expression pretreatment, during treatment and at progression
Time frame: 12 weeks
Population: Blood samples were collected. However, due to the lack of ASPH-specific T-cell responses in patients treated with SNS-301 and the subsequent discontinuation of the clinical trial, the samples were not analyzed and no data were generated.