Trial Outcomes & Findings for Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma (NCT NCT04044768)

This was a Phase 2, single-arm, open-label study of afamitresgene autoleucel in HLA-A\*02+ participants with MAGE-A4 expressing metastatic or inoperable (advanced) synovial sarcoma or myxoid/round cell liposarcoma (MRCLS) (Cohort 1). Eligible participants received between 1.0 × 10\^9 to 10.0 × 10\^9 transduced cells of afamitresgene autoleucel, administered as a single IV infusion following lymphodepletion with fludarabine and cyclophosphamide.

NOTE: Cohort 1 participant Flow, demographics and efficacy cut off was 29Aug2022; Cohort 1 safety cut off was 29Mar2023

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

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)

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.

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

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.

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.

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.

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

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.

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

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

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

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

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

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