Back to resultsSPEARHEAD-3 Pediatric Study
Primary Purpose
Synovial Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST), Neuroblastoma
Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Afamitresgene autoleucel
Sponsored by
About this trial
This is an interventional treatment trial for Synovial Sarcoma
Eligibility Criteria
Inclusion Criteria: Age 2-21 years Body weight ≥ 10 kg Subject has histologically confirmed diagnosis of any one of the following cancers: (A) Synovial Sarcoma, (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma Must have previously received a systemic chemotherapy Measurable disease according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only). HLA-A*02 positive Tumor shows MAGE-A4 expression confirmed by central laboratory. Performance Status: ECOG 0-1 or Lansky Score ≥ 80 Exclusion Criteria: HLA-A*02:05 in either allele; or any A*02 having same protein sequence as HLA-A*02:05 History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide. History of autoimmune or immune mediated disease Known central nervous system (CNS) metastases. Other prior malignancy that is not considered by the Investigator to be in complete remission Clinically significant cardiovascular disease Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus Pregnant or breastfeeding
Sites / Locations
- Stanford University
- University of Colorado
- National Institue of Health
- Dana Farber Cancer Institute
- Washington University
- Memorial Sloan Kettering Kids
- Duke University School of Medicine
- Cincinnati Children's Hospital Medical Center
- Children's Hospital of Philedephia
- UT Southwestern Medical Center
- Seattle Children's Hospital
- University of Wisconsin Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Afamitresgene autoleucel
Arm Description
Outcomes
Primary Outcome Measures
Incidence, duration, and severity of Treatment Emergent Adverse Events as assessed by Investigator Evaluation.
Determination of incidence, severity and duration of adverse events
Incidence of dose limiting toxicities DLTs
AEs including serious adverse events (SAEs)
Incidence, severity, and duration of the AEs of special interest
Replication competent lentivirus (RCL)
T-cell clonality and insertional oncogenesis (IO)
Secondary Outcome Measures
Efficacy: Objective response rate (ORR) assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (or by International Neuroblastoma Response Criteria [INRC] 2017 in NB subjects)
ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 or INRC, 2017
Time to response (TTR)
For patients who are observed to respond to afamitresgene autoleucel in the time from date of infusion to achieve a partial response or complete response (TTR) is assessed
Duration of Response (DoR)
For patients who are observed to respond to afamitresgene autoleucel the DoR is the date of initial response (including confirmation) from date of infusion up until disease progression
Best overall response (BOR)
BOR is assessed by the investigator per RECIST V1.1 or INCR, 2017 (for NB subjects)
Progression Free Survival (PFS)
PFS is assessed by the investigator from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or INCR, 2017 (for NB subjects) or death.
Overall Survival (OS)
OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death.
Pharmacokinetics (PK). Characterize the in vivo cellular pharmacokinetics (PK) profile of afamitresgene autoleucel by evaluation of PBMC samples for peak persistence.
Obtain PBMC samples for the evaluation of peak persistence of afamitresgene autoleucel.
Development and validation of an invitro diagnostic (IVD) assay for the screening of tumor antigen expression for regulatory approval.
Retention of additional tumor tissue during Pre-Screening to enable development and validation of the MAGE-A4 antigen expression companion diagnostic (CDx) assay.
Invitro diagnostic (IVD) assay for screening
Development and validation of the MAGE-A4 antigen expression companion diagnostic assay
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05642455
Brief Title
SPEARHEAD-3 Pediatric Study
Official Title
A Phase 1/2 Open Label, Basket Study to Assess the Safety, Tolerability and Anti-Tumor Activity of Afamitresgene Autoleucel in Pediatric Subjects With MAGE-A4 Positive Tumors
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 31, 2023 (Anticipated)
Primary Completion Date
October 1, 2026 (Anticipated)
Study Completion Date
July 30, 2038 (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 pediatric basket study to investigate the safety and efficacy of afamitresgene autoleucel in HLA-A*02 eligible and MAGE-A4 positive subjects aged 2-21 years of age with advanced cancers
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Synovial Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST), Neuroblastoma, Osteosarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Afamitresgene autoleucel
Arm Type
Experimental
Intervention Type
Genetic
Intervention Name(s)
Afamitresgene autoleucel
Intervention Description
Single infusion of afamitresgene autoleucel Dose: For subjects ≥10 kg to <40 kg: starting dose of 0.025 - 0.200 x 10'9 transduced cells/kg. For subjects ≥40 kg 1.0x109 to 10x109 transduced by a single intravenous infusion
Primary Outcome Measure Information:
Title
Incidence, duration, and severity of Treatment Emergent Adverse Events as assessed by Investigator Evaluation.
Description
Determination of incidence, severity and duration of adverse events
Incidence of dose limiting toxicities DLTs
AEs including serious adverse events (SAEs)
Incidence, severity, and duration of the AEs of special interest
Replication competent lentivirus (RCL)
T-cell clonality and insertional oncogenesis (IO)
Time Frame
3.5 years
Secondary Outcome Measure Information:
Title
Efficacy: Objective response rate (ORR) assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (or by International Neuroblastoma Response Criteria [INRC] 2017 in NB subjects)
Description
ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 or INRC, 2017
Time Frame
3.5 years
Title
Time to response (TTR)
Description
For patients who are observed to respond to afamitresgene autoleucel in the time from date of infusion to achieve a partial response or complete response (TTR) is assessed
Time Frame
3.5 years
Title
Duration of Response (DoR)
Description
For patients who are observed to respond to afamitresgene autoleucel the DoR is the date of initial response (including confirmation) from date of infusion up until disease progression
Time Frame
3.5 years
Title
Best overall response (BOR)
Description
BOR is assessed by the investigator per RECIST V1.1 or INCR, 2017 (for NB subjects)
Time Frame
3.5 years
Title
Progression Free Survival (PFS)
Description
PFS is assessed by the investigator from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or INCR, 2017 (for NB subjects) or death.
Time Frame
3.5 years
Title
Overall Survival (OS)
Description
OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death.
Time Frame
15 years
Title
Pharmacokinetics (PK). Characterize the in vivo cellular pharmacokinetics (PK) profile of afamitresgene autoleucel by evaluation of PBMC samples for peak persistence.
Description
Obtain PBMC samples for the evaluation of peak persistence of afamitresgene autoleucel.
Time Frame
3.5 years
Title
Development and validation of an invitro diagnostic (IVD) assay for the screening of tumor antigen expression for regulatory approval.
Description
Retention of additional tumor tissue during Pre-Screening to enable development and validation of the MAGE-A4 antigen expression companion diagnostic (CDx) assay.
Time Frame
3.5 years
Title
Invitro diagnostic (IVD) assay for screening
Description
Development and validation of the MAGE-A4 antigen expression companion diagnostic assay
Time Frame
3.5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 2-21 years
Body weight ≥ 10 kg
Subject has histologically confirmed diagnosis of any one of the following cancers: (A) Synovial Sarcoma, (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma
Must have previously received a systemic chemotherapy
Measurable disease according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only).
HLA-A*02 positive
Tumor shows MAGE-A4 expression confirmed by central laboratory.
Performance Status: ECOG 0-1 or Lansky Score ≥ 80
Exclusion Criteria:
HLA-A*02:05 in either allele; or any A*02 having same protein sequence as HLA-A*02:05
History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide.
History of autoimmune or immune mediated disease
Known central nervous system (CNS) metastases.
Other prior malignancy that is not considered by the Investigator to be in complete remission
Clinically significant cardiovascular disease
Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
Pregnant or breastfeeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tara O'Donohue, MD
Organizational Affiliation
Memorial Sloan Kettering Kids
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sneha Ramakrishna, MD
Facility Name
University of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045,
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Vanessa Fabrizio,, MD
Facility Name
National Institue of Health
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
80292
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Glod, MD
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
10065
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Natalie Collins, MD
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amy Armstrong, MD
Facility Name
Memorial Sloan Kettering Kids
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tara O'Donohue, MD
Facility Name
Duke University School of Medicine
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kris Mahadeo, MD
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Brian Turpin, MD
Facility Name
Children's Hospital of Philedephia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shelby Brizzolara-Dove, BS
Phone
267-425-5544
Email
CancerTrials@chop.edu
First Name & Middle Initial & Last Name & Degree
Theodore Laetsch, MD
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matt Campbell, MD
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Albert, MD
Facility Name
University of Wisconsin Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53715
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Capitini
12. IPD Sharing Statement
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SPEARHEAD-3 Pediatric Study
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