Back to resultsSPEARHEAD 2 Study in Subjects With Recurrent or Metastatic Head and Neck Cancer
Primary Purpose
Head and Neck Cancer
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ADP-A2M4 in combination with pembrolizumab.
Sponsored by
About this trial
This is an interventional treatment trial for Head and Neck Cancer focused on measuring Cell Therapy, T-cell Therapy, SPEAR T-Cell, Head and Neck Cancer, MAGE-A4, ADP-A2M4, Immuno-oncology
Eligibility Criteria
Key Inclusion Criteria
- Age ≥18 and <75 years
- Diagnosis of head and neck squamous cell carcinoma with metastatic or unresectable, recurrent disease. confirmed by histology cytology.
- Checkpoint inhibitor naïve and indicated for pembrolizumab or currently receiving pembrolizumab (monotherapy). May have received prior platinum containing chemotherapy regimen or checkpoint inhibitor therapy.
- Subjects that have already received pembrolizumab (alone or in combination) and are progressing or have completed immune checkpoint inhibitor therapy for recurrent/metastatic disease, may still be enrolled and will skip Part A of the study.
These subjects will enroll into Part B when manufactured T cells are available.
- Measurable disease according to RECIST v1.1.
- HLA-A*02 positive by central laboratory.
- Tumor shows MAGE-A4 expression confirmed by central laboratory.
- ECOG Performance Status of 0 or 1.
- Left ventricular ejection fraction (LVEF) ≥50%.
Note: other protocol defined Inclusion criteria may apply
Key Exclusion Criteria:
- Positive for any HLA-A*02 allele other than: one of the inclusion alleles, HLA- A*02:07P or HLA-A*02 null alleles
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study or history of severe hypersensitivity to another monoclonal antibody.
- History of autoimmune or immune mediated disease
- Leptomeningeal disease, carcinomatous meningitis or CNS metastases.
- Other prior malignancy that is not considered by the Investigator to be in complete remission
- Clinically significant cardiovascular disease
- Uncontrolled intercurrent illness
- Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
- Pregnant or breastfeeding
Note: other protocol defined Exclusion criteria may apply.
Sites / Locations
- Mayo Clinic Phoenix
- University of California San Diego
- University of Kansas Medical Center
- Karmanos Cancer Insitute
- Providence Cancer Institute Franz Head and Neck Clinic
- Vanderbilt-Ingram Cancer Center
- MD Anderson Cancer Center
- West Virginia University Cancer Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ADP-A2M4 T cells in combination with pembrolizumab
Arm Description
Outcomes
Primary Outcome Measures
Efficacy: Overall Response Rate (ORR)
ORR is defined as the proportion of complete responses or partial responses as assessed by RECIST v1.1
Secondary Outcome Measures
Best overall response (BOR)
BOR defined as the best response recorded from the date of T cell infusion until disease progression.
Time to response (TTR)
TTR defined as the duration between T cell infusion and the initial date of the confirmed response.
Duration of response (DoR)
DoR defined as the duration from the initial date of the confirmed response to the date of PD (or death).
Duration of stable disease (DoSD)
DoSD defined as the duration from the date of T cell infusion to the date of PD (or death).
Progression- free survival (PFS)
PFS defined as the interval between the date T cell infusion and the earliest date of disease progression based on RECIST v1.1 or death due to any cause.
Overall survival (OS)
OS defined the duration between T cell infusion and death due to any cause.
To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining incidence of Adverse events (AEs) including serious adverse events (SAEs)
Determination of incidence, severity and duration of adverse events through assessment of adverse events including SAEs. Adverse events will be collected and graded as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining the incidence, severity and duration of the AEs of special interest
Adverse events of special interest will be listed along with duration and toxicity grade.
To evaluate safety of ADP-A2M4 with pembrolizumab through measurement of Replication-competent Lentivirus in genetically engineered T-cells
Evaluation of RCL using PCR-based assay in peripheral blood.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04408898
Brief Title
SPEARHEAD 2 Study in Subjects With Recurrent or Metastatic Head and Neck Cancer
Official Title
A Phase 2 Pilot Study of ADP-A2M4 in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Head and Neck Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
November 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Challenges with recruitment
Study Start Date
July 2, 2020 (Actual)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2021 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Adaptimmune
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This is a study to investigate the efficacy and safety of ADP-A2M4 in combination with pembrolizumab in HLA-A*02 eligible and MAGE-A4 positive subjects with recurrent or metastatic Head and Neck cancer.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
Cell Therapy, T-cell Therapy, SPEAR T-Cell, Head and Neck Cancer, MAGE-A4, ADP-A2M4, Immuno-oncology
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ADP-A2M4 T cells in combination with pembrolizumab
Arm Type
Experimental
Intervention Type
Genetic
Intervention Name(s)
ADP-A2M4 in combination with pembrolizumab.
Intervention Description
Single infusion of autologous genetically modified ADP-A2M4 Dose: 1.0 x109 to 10x109 transduced cells by a single intravenous infusion Repeat doses of pembrolizumab every 3 weeks. Dose: 200mg
Primary Outcome Measure Information:
Title
Efficacy: Overall Response Rate (ORR)
Description
ORR is defined as the proportion of complete responses or partial responses as assessed by RECIST v1.1
Time Frame
2.5 years
Secondary Outcome Measure Information:
Title
Best overall response (BOR)
Description
BOR defined as the best response recorded from the date of T cell infusion until disease progression.
Time Frame
2.5 years
Title
Time to response (TTR)
Description
TTR defined as the duration between T cell infusion and the initial date of the confirmed response.
Time Frame
2.5 years
Title
Duration of response (DoR)
Description
DoR defined as the duration from the initial date of the confirmed response to the date of PD (or death).
Time Frame
2.5 years
Title
Duration of stable disease (DoSD)
Description
DoSD defined as the duration from the date of T cell infusion to the date of PD (or death).
Time Frame
2.5 years
Title
Progression- free survival (PFS)
Description
PFS defined as the interval between the date T cell infusion and the earliest date of disease progression based on RECIST v1.1 or death due to any cause.
Time Frame
2.5 years
Title
Overall survival (OS)
Description
OS defined the duration between T cell infusion and death due to any cause.
Time Frame
2.5 years
Title
To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining incidence of Adverse events (AEs) including serious adverse events (SAEs)
Description
Determination of incidence, severity and duration of adverse events through assessment of adverse events including SAEs. Adverse events will be collected and graded as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Time Frame
2.5 years
Title
To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining the incidence, severity and duration of the AEs of special interest
Description
Adverse events of special interest will be listed along with duration and toxicity grade.
Time Frame
2.5 years
Title
To evaluate safety of ADP-A2M4 with pembrolizumab through measurement of Replication-competent Lentivirus in genetically engineered T-cells
Description
Evaluation of RCL using PCR-based assay in peripheral blood.
Time Frame
15 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria
Age ≥18 and <75 years
Diagnosis of head and neck squamous cell carcinoma with metastatic or unresectable, recurrent disease. confirmed by histology cytology.
Checkpoint inhibitor naïve and indicated for pembrolizumab or currently receiving pembrolizumab (monotherapy). May have received prior platinum containing chemotherapy regimen or checkpoint inhibitor therapy.
Subjects that have already received pembrolizumab (alone or in combination) and are progressing or have completed immune checkpoint inhibitor therapy for recurrent/metastatic disease, may still be enrolled and will skip Part A of the study.
These subjects will enroll into Part B when manufactured T cells are available.
Measurable disease according to RECIST v1.1.
HLA-A*02 positive by central laboratory.
Tumor shows MAGE-A4 expression confirmed by central laboratory.
ECOG Performance Status of 0 or 1.
Left ventricular ejection fraction (LVEF) ≥50%.
Note: other protocol defined Inclusion criteria may apply
Key Exclusion Criteria:
Positive for any HLA-A*02 allele other than: one of the inclusion alleles, HLA- A*02:07P or HLA-A*02 null alleles
History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study or history of severe hypersensitivity to another monoclonal antibody.
History of autoimmune or immune mediated disease
Leptomeningeal disease, carcinomatous meningitis or CNS metastases.
Other prior malignancy that is not considered by the Investigator to be in complete remission
Clinically significant cardiovascular disease
Uncontrolled intercurrent illness
Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
Pregnant or breastfeeding
Note: other protocol defined Exclusion criteria may apply.
Facility Information:
Facility Name
Mayo Clinic Phoenix
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
University of California San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Karmanos Cancer Insitute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Providence Cancer Institute Franz Head and Neck Clinic
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
West Virginia University Cancer Institute
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
12. IPD Sharing Statement
Learn more about this trial
SPEARHEAD 2 Study in Subjects With Recurrent or Metastatic Head and Neck Cancer
We'll reach out to this number within 24 hrs