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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma.

Sandra P D'Angelo1, Mihaela Druta2, Brian A Van Tine3

  • 1Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|January 21, 2025
PubMed
Summary
This summary is machine-generated.

This pilot study shows promising results for letetresgene autoleucel (lete-cel) in advanced myxoid/round cell liposarcoma (MRCLS) patients. The adoptive T-cell therapy demonstrated clinical activity and T-cell expansion in NY-ESO-1-positive individuals.

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Area of Science:

  • Oncology
  • Immunotherapy
  • Cancer Genetics

Background:

  • Myxoid/round cell liposarcoma (MRCLS) is a rare soft tissue sarcoma.
  • The cancer/testis antigen New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is expressed in MRCLS, making it a potential therapeutic target.
  • Adoptive T-cell therapy offers a novel approach to target cancer-specific antigens.

Purpose of the Study:

  • To evaluate the safety and efficacy of letetresgene autoleucel (lete-cel), an adoptive T-cell therapy targeting NY-ESO-1, in patients with advanced or metastatic MRCLS.
  • To assess the clinical response in patients positive for human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05, and/or HLA-A*02:06.

Main Methods:

  • A pilot study involving two cohorts of patients with advanced/metastatic NY-ESO-1-expressing MRCLS.
  • Patients received lete-cel after a reduced-dose (cohort 1) or standard-dose (cohort 2) lymphodepletion regimen (LDR).
  • Overall response rate (ORR) was the primary endpoint; safety and correlative biomarker analyses were also conducted.

Main Results:

  • Of 20 treated patients, ORR was 20% in cohort 1 and 40% in cohort 2.
  • Median duration of response was 5.3 months (cohort 1) and 7.5 months (cohort 2).
  • Median progression-free survival was 5.4 months (cohort 1) and 8.7 months (cohort 2); T-cell expansion and persistence were observed.

Conclusions:

  • Letetresgene autoleucel (lete-cel) demonstrates clinical promise in HLA and NY-ESO-1-positive patients with advanced MRCLS.
  • This study provides the first evidence of lete-cel's potential in this patient population.
  • The observed T-cell expansion and persistence support the mechanism of action for this adoptive T-cell therapy.