Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma
Condition: Neoplasms
MeSH terms: Liposarcoma; Liposarcoma, Myxoid
Intervention: letetresgene autoleucel (GSK3377794); Cyclophosphamide; Fludarabine
Intervention description: Letetresgene autoleucel (GSK3377794) as an IV infusion.; Cyclophosphamide will be used as a lymphodepleting chemotherapy.; Fludarabine will be used as a lymphodepleting chemotherapy.
Intervention MeSH terms: Cyclophosphamide; Fludarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myxoid/ round cell liposarcoma; Letetresgene autoleucel; Immuno-oncology; T Cell Receptor; Leukapheresis; NY-ESO-1; Adoptive TCR T-cell therapy

Summary:

      This trial will evaluate safety and efficacy of Letetresgene autoleucel (GSK3377794) in
      participants with advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant is greater than equal to (>=)18 years of age at the time of signing the
             study informed consent.

          -  Participant has a diagnosis of advanced (metastatic or inoperable) high grade myxoid
             liposarcoma / myxoid round cell liposarcoma confirmed histologically and by the
             presence of the reciprocal chromosomal translocation t(12;16) (q13;p11) or t(12; 22)
             (q13;q12).

          -  Participant has measurable disease according to RECIST v1.1 criteria.

          -  Participant must have previously received or be intolerant to anthracycline based
             therapy for advanced (metastatic or inoperable) disease.

          -  Participants who received neoadjuvant/adjuvant anthracycline based therapy and
             progressed within 6 months of completion of therapy will be eligible.

          -  Participant must be HLA A*02:01, HLA A*02:05 and/or HLA-A*02:06 positive.

          -  Participant's tumor (either the most recent archival specimen or a fresh biopsy) is
             positive for NY-ESO-1 expression by a designated central laboratory.

          -  Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.

          -  Participant has a left ventricular ejection fraction >=45%.

          -  Participant is fit for apheresis and has adequate venous access for the cell
             collection.

          -  Participants must satisfy pregnancy and contraceptive requirements per protocol and
             have adequate organ function per protocol specified values.

        Exclusion Criteria:

          -  Any previous gene therapy using an integrating vector.

          -  Any previous allogeneic hematopoietic stem cell transplant.

          -  Participant has history of allergic reactions attributed to compounds of similar
             chemical or biologic composition to fludarabine, cyclophosphamide or other agents used
             in the study.

          -  Participant has history of chronic or recurrent (within the last year prior to
             screening) severe autoimmune or immune mediated disease requiring steroids or other
             immunosuppressive treatments.

          -  Participant has known active brain or leptomeningeal metastases.

          -  Participant has other prior malignancy that is not in complete remission.

          -  Participant has uncontrolled intercurrent illness including, but not limited to:

          -  (i) Ongoing or active infection.

          -  (ii) Clinically significant cardiac disease

          -  (iii) Interstitial lung disease (participants with existing pneumonitis as a result of
             radiation are not excluded, however, participants must not be oxygen dependent).

          -  Participant has active infection with Human Immunodeficiency Virus (HIV), Hepatitis B
             virus (HBV), ), Hepatitis C virus (HCV) or human T-lymphotropic virus (HTLV).