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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.
Purpose:
The cancer/testis antigen New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a promising target in myxoid/round cell liposarcoma (MRCLS).
Methods:
In this pilot study, we assessed the adoptive T-cell therapy NY-ESO-1c259T letetresgene autoleucel (lete-cel) in patients with human leukocyte antigen (HLA)-A*02:01-, HLA-A*02:05-, and/or HLA-A*02:06-positive advanced/metastatic NY-ESO-1-expressing MRCLS. Patients underwent a reduced-dose (cohort 1) or standard-dose (cohort 2) lymphodepletion regimen (LDR). The primary end point was investigator-assessed overall response rate (ORR). Safety was assessed through adverse event (AE) reports. Correlative biomarker analyses were performed post hoc. The trial is registered at ClinicalTrials.gov (identifier: NCT02992743).
Results:
Of 23 enrolled patients, 10 in cohort 1 and 10 in cohort 2 received lete-cel. Investigator-assessed ORR was 20% (95% CI, 2.5 to 55.6) and 40% (95% CI, 12.2 to 73.8), median duration of response was 5.3 months (95% CI, 1.9 to 8.7) and 7.5 months (95% CI, 6.0 to not estimable [NE]), and median progression-free survival was 5.4 months (95% CI, 2.0 to 11.5) and 8.7 months (95% CI, 0.9 to NE) in cohorts 1 and 2, respectively. AEs included cytokine release syndrome and cytopenias, consistent with T-cell therapy/LDR. Post hoc correlative biomarkers showed T-cell expansion and persistence in both cohorts.
Conclusion:
To our knowledge, this study is the first demonstrating the clinical promise of lete-cel in HLA-/NY-ESO-1-positive patients with advanced MRCLS.
Insights
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.
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.
