Clinical trial NCT04044768: Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
Official title: A Phase 2 Single Arm Open-Label Clinical Trial of ADP-A2M4 SPEAR™ T Cells in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Synovial Sarcoma
Myxoid Liposarcoma
Keywords: Cell Therapy
T Cell Therapy
SPEAR T Cell
Sarcoma
MRCLS
MAGE A-4
Immuno-oncology
Lead sponsor: Adaptimmune
Sponsor class: INDUSTRY
First posted: 2019-08-05
Enrollment: 52
Sex: ALL
Minimum age (years): 10
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a study to investigate the efficacy and safety of ADP-A2M4 in HLA-A\*02 eligible and MAGE-A4 positive subjects with metastatic or inoperable (advanced) Synovial Sarcoma (Cohort 1, 2 and 3 ) or MRCLS (Cohort 1) .


Eligibility criteria: Key Inclusion Criteria

* Age ≥16 (10 years at selected sites) and \<=75 years
* Diagnosis of advanced synovial sarcoma (Cohort 1, Cohort 2 and Cohort 3) or myxoid liposarcoma / myxoid round cell liposarcoma (Cohort 1 only) confirmed by cytogenetics.
* Previously received either an anthracycline or ifosfamide containing regimen.
* Measurable disease according to RECIST v1.1 prior to lymphodepletion
* HLA-A\*02:01, HLA-A\*02:02, HLA-A\*02:03 or HLA-A\*02:06 positive
* Tumor shows MAGE-A4 expression confirmed by central laboratory. North America Only (United States and Canada): Tumor (either an archival specimen or a fresh biopsy) shows MAGE-A4 expression of ≥1+ staining in ≥10% of the cells by immunohistochemistry.
* ECOG Performance Status of 0 or1. For subjects aged ≥10 to ≥16 years old:

Lansky Score ≥60%.

• Left ventricular ejection fraction (LVEF) ≥50%.

Note: other protocol defined Inclusion criteria may apply

Key Exclusion Criteria:

* HLA-A\*02:05 in either allele
* Received or plans to receive the following therapy/treatment prior to leukapheresis or lymphodepleting chemotherapy: Cytotoxic chemotherapy, Tyrosine kinase inhibitor (TKI) (e.g. pazopanib), Immune therapy (including monoclonal antibody therapy, checkpoint inhibitors,), Anti-cancer Vaccine, Gene therapy using an integrating vector (subjects who have received a gene therapy using a lentiviral vector may be eligible for the study), Corticosteroids or any other immunosuppressive therapy, Investigational treatment or interventional clinical trial, Allogeneic hematopoietic stem cell transplant, Radiotherapy to the target lesions, Major surgery
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
* History of autoimmune or immune mediated disease
* Symptomatic CNS metastases including leptomeningeal disease.
* 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.

Primary outcomes:
measure: Overall Response Rate (ORR) (Cohort 1)
timeFrame: From T-cell infusion until disease progression/recurrence as of data cut off (up to 2 years). Response was assessed at Week 4, Week 8, Week 12, Week 16, and Week 24, and every 2 months +/- 28 days until confirmed disease progression.
Secondary outcomes:
measure: Adverse Events (AE) Including Serious Adverse Events (SAE), SAE, and Adverse Events of Special Interest (AESI) (Cohort 1)
timeFrame: AEs, SAEs, and AESIs were collected at each visit from the start of lymphodepletion of the first subject until the last subject discontinued the interventional phase in cohort 1 as of the safety cut off (up to 3.2 years).
measure: The Number of Participants With Replication Competent Lentivirus (RCL)
timeFrame: From T-cell infusion to months 3, 6, and 12 post-infusion, then annually post-infusion (up to 2.8 years as of the data cut off).
measure: Insertional Oncogenesis (IO)
timeFrame: From 10 months post T-cell infusion up to 20 months post T-cell infusion (as of the data cut off)
measure: Best Overall Response (BOR) (Cohort 1)
timeFrame: From T-cell infusion until disease progression/recurrence as of data cut off (up to 2.6 years). Response was assessed at Week 4, Week 8, Week 12, Week 16, and Week 24, and every 2 months +/- 28 days until confirmed disease progression.
measure: Time to Response (TTR) (Cohort 1)
timeFrame: From T-cell infusion until first documented confirmed CR or confirmed PR. Response was assessed at Week 4, Week 8, Week 12, Week 16, and Week 24, and every 2 months +/- 28 days until confirmed disease progression.
measure: Duration of Response (DoR) (Cohort 1)
timeFrame: From initial confirmed response (CR or PR) until PD (or censored date) as of data cut off.
measure: Progression Free Survival (PFS) (Cohort 1)
timeFrame: From T-cell infusion until first documented PD or death due to any cause (or censored date), whichever occurs first, as of data cut off (up to 2.6 years). Response was assessed at Week 4, 8,12,16, 24, and every 2 months until confirmed PD
measure: Overall Survival (OS) (Cohort 1)
timeFrame: From T-cell infusion to death due to any reason (or censored date) as of data cut off (up to 2.6 years).
measure: Peak Persistence (Cohort 1)
timeFrame: From T-cell infusion to 3.2 years (as of data cut off).
measure: Time Taken to Achieve Peak Expansion of Genetically Engineered T-cells in PBMCs
timeFrame: 2.5 years
measure: Quantitation of Genetically Engineered T-cells in PBMCs
timeFrame: 2.5 years
measure: Time Taken to Achieve Peak Expansion of Genetically Engineered T-cells in PBMCs
timeFrame: 2.5 years
measure: In Vitro Diagnostic (IVD) Assay for Screening
timeFrame: 2.5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic Jacksonville
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Bethesda
country: United States
facility: National Cancer Institute
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutch
state: Washington
city: Milwaukee
country: United States
facility: Medical College of WI Froedtert Hospital
state: Wisconsin
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Lyon
country: France
facility: Centre Leon Berard
city: Pessac
country: France
facility: Hospital Haut Leveque, CHU Bordeaux
city: Villejuif
country: France
facility: Gustave Roussy Cancer Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
state: Cataluna
city: Madrid
country: Spain
facility: Start Madrid-FJD, Fundación Jimѐnez Díaz
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: London
country: United Kingdom
facility: UCLH Cancer Clinical Trials Unit
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: MD Anderson Cancer Center; Houston TX 77030
name: Dejka Araujo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: D'Angelo SP, Araujo DM, Abdul Razak AR, Agulnik M, Attia S, Blay JY, Carrasco Garcia I, Charlson JA, Choy E, Demetri GD, Druta M, Forcade E, Ganjoo KN, Glod J, Keedy VL, Le Cesne A, Liebner DA, Moreno V, Pollack SM, Schuetze SM, Schwartz GK, Strauss SJ, Tap WD, Thistlethwaite F, Valverde Morales CM, Wagner MJ, Wilky BA, McAlpine C, Hudson L, Navenot JM, Wang T, Bai J, Rafail S, Wang R, Sun A, Fernandes L, Van Winkle E, Elefant E, Lunt C, Norry E, Williams D, Biswas S, Van Tine BA. Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial. Lancet. 2024 Apr 13;403(10435):1460-1471. doi: 10.1016/S0140-6736(24)00319-2. Epub 2024 Mar 27.
citation: Sanderson JP, Crowley DJ, Wiedermann GE, Quinn LL, Crossland KL, Tunbridge HM, Cornforth TV, Barnes CS, Ahmed T, Howe K, Saini M, Abbott RJ, Anderson VE, Tavano B, Maroto M, Gerry AB. Preclinical evaluation of an affinity-enhanced MAGE-A4-specific T-cell receptor for adoptive T-cell therapy. Oncoimmunology. 2019 Nov 24;9(1):1682381. doi: 10.1080/2162402X.2019.1682381. eCollection 2020.