Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

Phase 2Active Not RecruitingNCT04044768

USWM CT, LLC52 enrolled

Overview

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) .

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Synovial Sarcoma Myxoid Liposarcoma

Interventions

afamitresgene autoleucel (previously ADP-A2M4)GENETIC

Single infusion of autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) Dose: 1.0 x109 to 10x109 transduced by a single intravenous infusion

Eligibility

Sex: ALLMin age: 10 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (26)

City of Hope

Duarte, California, United States

Outcomes

Primary Outcomes

Overall Response Rate (ORR) (Cohort 1)

Percentage of participants with confirmed tumor response (complete \[CR\] or partial \[PR\] response) to treatment as assessed using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 by Independent Radiologist review (Cohort 1)

Time frame: 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

Adverse Events (AE) Including Serious Adverse Events (SAE), SAE, and Adverse Events of Special Interest (AESI) (Cohort 1)

An AE was defined as any untoward medical occurrence in a subject or clinical study participant temporally associated with the use of the study intervention, whether or not considered related to the study intervention. Therefore, an AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. The number of participants with AEs (including SAE), SAE and AESI including cytokine release syndrome, neurotoxicity, ICANS, prolonged cytopenia are presented.

Time frame: 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).

The Number of Participants With Replication Competent Lentivirus (RCL)

The presence of RCL was assessed by qPCR targeting a segment of the vesicular stomatitis virus glycoprotein (VSV G) coding sequence.

Time frame: 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).

Insertional Oncogenesis (IO)

Deoxyribonucleic acid (DNA) from participants peripheral blood mononuclear cell (PBMC) samples was subjected to lentiviral vector integration site analysis by next-generation sequencing, thus evaluating both the clonality status of the transduced cell population and the genomic localization of individual integration sites. The count of participants with integration sites representing more than 5% of all unique sites is presented.

Data from ClinicalTrials.gov

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Stanford Cancer Center

Palo Alto, California, United States

University of Colorado

Aurora, Colorado, United States

Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Moffitt Cancer Center

Tampa, Florida, United States

Northwestern University Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, United States

National Cancer Institute

Bethesda, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

...and 16 more locations

Time frame: From 10 months post T-cell infusion up to 20 months post T-cell infusion (as of the data cut off)

Best Overall Response (BOR) (Cohort 1)

BOR is the best response recorded from the start of T-cell infusion until disease progression/recurrence as assessed by Independent Radiologist review. Response categories are confirmed CR, confirmed PR, stable disease and confirmed progressive disease (PD). Best overall response is a stable disease, if CR or PR are unconfirmed.

Time frame: 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.

Time to Response (TTR) (Cohort 1)

TTR was defined as the interval (weeks) from the date of T-cell infusion to the earliest date of the first documented confirmed CR or confirmed PR as assessed by Independent Radiologist review. TTR (in weeks) = \[date of initial confirmed CR or PR - date of T-cell infusion + 1\]/7.

Time frame: 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.

Duration of Response (DoR) (Cohort 1)

DoR (in months) is defined as ((date of PD (or censoring) - date of initial confirmed CR/PR + 1)/365.25)\*12 as assessed by Independent Radiologist review. Outcome Measure not yet reached as participants are ongoing in study

Time frame: From initial confirmed response (CR or PR) until PD (or censored date) as of data cut off.

Progression Free Survival (PFS) (Cohort 1)

PFS is defined as the time from T-cell infusion to the date of the first documentation of PD or death due to any cause, whichever occurs first, as assessed by Independent Radiologist review. PFS (in weeks) was calculated as (date of PD/death \[or censored date\] - first T-cell infusion date + 1)/7.

Time frame: 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

Overall Survival (OS) (Cohort 1)

OS is defined as the time from the date of T-cell infusion to the date of death (due to any reason) or censored date. OS in months was calculated as ((death date - first T-cell infusion date + 1)/365.25)\*12. Outcome Measure not yet reached as participants are ongoing in study

Time frame: From T-cell infusion to death due to any reason (or censored date) as of data cut off (up to 2.6 years).

Peak Persistence (Cohort 1)

Peak persistence of afamitresgene autoleucel cells was reported as vector copy numbers per microgram of genomic DNA from peripheral blood mononuclear cell (PBMC).

Time frame: From T-cell infusion to 3.2 years (as of data cut off).

Time Taken to Achieve Peak Expansion of Genetically Engineered T-cells in PBMCs

Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by flow cytometry

Time frame: 2.5 years

Quantitation of Genetically Engineered T-cells in PBMCs

Quantitation of genetically engineered T-cells in PBMCs by flow cytometry

Time frame: 2.5 years

Time Taken to Achieve Peak Expansion of Genetically Engineered T-cells in PBMCs

Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by qPCR

Time frame: 2.5 years

In Vitro Diagnostic (IVD) Assay for Screening

Development and validation of the MAGE-A4 antigen expression companion diagnostic assay

Time frame: 2.5 years