LETETRESGENE AUTOLEUCEL for Synovial sarcoma | Myxoid liposarcoma | Round cell liposarcoma

Inclusion criteria

• {"criterion_text":"- 1. For participants <18 years of age, (or the legal minimum age in the relevant country) their legal guardian must give informed consent. Pediatric subjects will be included in age-appropriate discussion in order to obtain assent.\n- 9.Participant is either currently being treated with or has completed at least one standard-of-care treatment including anthracycline-containing regimens (e.g., doxorubicin alone, doxorubicin with ifosfamide) for advanced disease. Participants who are intolerant to anthracycline may receive ifosfamide alone unless intolerant to or ineligible to receive ifosfamide. Participants who received anthracycline-based therapy in the neoadjuvant/adjuvant setting and progressed will be eligible.\n- 10.Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a validated test in a designated central lab prior to leukapheresis.\n- 11.Participant's tumor has been pathologically reviewed by a designated central laboratory with confirmed positive NY-ESO-1 expression defined as ≥30% of cells that are 2+ or 3+ by immunohistochemistry.\n- 12. Left ventricular ejection fraction ≥45% with no evidence of clinically significant pericardial effusion.\n- 13. Performance status: for participants <16 years of age, Lansky >60, or for participants ≥16 and <18 years of age, Karnofsky >60, or for participants ≥18 years of age, Eastern Cooperative Oncology Group (ECOG) of 0-1.\n- 14.Participant must have adequate organ function and blood cell counts, within 7 days prior to the day of leukapheresis procedure, as indicated in the protocol. For a detailed list of Inclusion Criteria, please refer to the protocol section 6.1.\n- For a detailed list of Inclusion Criteria, please refer to the protocol Page No. 173-178\n- 2.Participant must be ≥10 years of age at the time of signing the informed consent. Participant scheduled to receive clinical drug product supply must weigh ≥40 kg. For participant scheduled to receive intended commercial drug product supply and weighing <40kg, the Investigator must also consult with the Medical Monitor prior to inclusion.\n- 3.Participant has a diagnosis of synovial sarcoma or myxoid/ round cell liposarcoma, confirmed by local histopathology and with evidence of disease-specific translocation\n- 4. Participant has advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma.\n- 5. Male or female. Contraception requirements will apply at the time of leukapheresis and treatment.\n- 6. A representative tumor tissue specimen (archived or fresh biopsy) with associated pathology report should be available to perform NY-ESO-1 antigen expression analysis, unless a recent NY-ESO-1 expression test result from the same designated central laboratory, following the same procedures, has already been performed under a separate company sponsored protocol or under another substudy.\n- Leukapheresis Eligibility Screening All the Inclusion Criteria from Section 6.1.1 must apply again prior to leukapheresis. In addition, the following criteria must also apply:\n- 7. Life expectancy ≥24 weeks\n- 8. Participant has confirmed evidence of a relevant disease-specific translocation per below: • For synovial sarcoma, presence of a translocation involving chromosome 18 (SYT gene) and/or chromosome X (SSX1, SSX2 or SSX4 genes); • For myxoid/round cell liposarcoma, presence of a translocation involving chromosome 12 (DDIT3 gene) and/or chromosome 16 (FUS gene) and/or chromosome 22 (EWSR1 gene)."}

Exclusion criteria

• {"criterion_text":"- 1.Participant has been previously treated for advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma.\n- 9.Participant has history of chronic or recurrent severe autoimmune or immune mediated disease (e.g. Crohn's disease, systemic lupus) requiring steroids or other immunosuppressive treatments.\n- 10. Uncontrolled intercurrent illness including, but not limited to: a. Ongoing or active infection b. Clinically significant cardiac disease defined by congestive heart failure New York Heart Association (NYHA) Class 3 /Class 4 c. Uncontrolled clinically significant arrhythmia d. Acute coronary syndrome (angina or myocardial infarction) in last 6 months\n- 11. Current active liver or biliary disease.\n- 12. QTc >480 msec\n- 13. Participant has a history of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, other agents used in the study.\n- 14. Pregnant or breastfeeding females\n- 15. Prior/concomitant therapy: any prior treatment-related toxicities must be Common terminology criteria for adverse events <=Grade 1 at the time of initiating study intervention (except for non-clinically significant toxicities). Other lines of therapy are allowed only if guidelines and washout periods are followed.\n- 16. Investigational treatment within 30 days or 5 half-lives (whichever is shorter) prior to leukapheresis. Investigational vaccines (other than NY-ESO-1 vaccines that are not allowed) must follow washout periods in the protocol.\n- 17. Participant has active infection with HIV, HBV, HCV, EBV, CMV, syphilis, or HTLV as defined in the protocol\n- 18. Has known psychiatric or substance abuse disorders that would interfere with cooperating with study requirements.\n- 2. Central nervous system metastases.\n- Mandatory washout periods must be respected before starting lymphodepletion. In addition to confirming treatment fitness (Section 6.2.3.1), participants cannot proceed with lymphodepletion or treatment if any of the following criteria apply:\n- 19. Participant has received cytotoxic therapy within 3 weeks prior to lymphodepleting chemotherapy.\n- 20. Systemic corticosteroids or any other immunosuppressive therapy within 2 weeks prior to lymphodepleting chemotherapy.\n- 21. Participant has received ≥50 Gy to a significant volume of the pelvis, long bones or spine, or a cumulative dose of radiation that, in the Investigator's opinion would predispose patients to prolonged cytopenia after lymphodepletion.\n- 22. All of the participant's measurable lesions have been irradiated within 3 months prior to lymphodepletion.\n- 23.Participant has received live vaccine within 4 weeks prior to lymphodepletion or intends to receive live vaccine during the 3 month period following administration of GSK3377794. For a detailed list of Exclusion Criteria, please refer to protocol section 6.2.\n- For a detailed list of Exclusion Criteria, please refer to protocol pages 178-182.\n- 3. Any other prior malignancy that is not in complete remission.\n- 4. Previous treatment with genetically engineered NY-ESO-1-specific T cells.\n- 5. Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.\n- 6. Prior gene therapy using an integrating vector.\n- 7. Previous allogeneic hematopoietic stem cell transplant.\n- 8. Clinically significant systemic illness: serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction, that in the judgment of the Investigator would compromise the subject's ability to tolerate protocol therapy or significantly increase the risk of complications, or prior or active demyelinating disease.\n- Leukapheresis Eligibility Screening: Participants are not eligible if any of the exclusion criteria (section 6.2.1) apply. Please note that mandatory washout periods must be respected before starting leukapheresis. In addition, participants are not eligible if any of the following apply:"}

Primary endpoints

• {"endpoint_text":"- Overall Response Rate (ORR) per RECIST v1.1","definition_or_measurement_approach":"Assessed per RECIST v1.1 criteria"}

Secondary endpoints

• {"endpoint_text":"- To evaluate efficacy of NY-ESO -1 ∙ Time to Response (TTR) ∙ Duration of Response (DoR) ∙ Disease Control Rate (DCR) ∙ Progression Free Survival (PFS)","definition_or_measurement_approach":"Efficacy outcomes including Time to Response, Duration of Response, Disease Control Rate and Progression Free Survival as typically defined (TTR, DoR, DCR, PFS); specific measurement per protocol (RECIST v1.1 for response assessments)."}
• {"endpoint_text":"- To evaluate safety and tolerability of NY-ESO-1 ∙ Frequency and severity of Adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI; as defined in protocol) ∙ Laboratory parameters ∙ Replication Competent Lentivirus (RCL) ∙ Instances of Insertional oncogenesis (IO)","definition_or_measurement_approach":"Safety assessed by frequency and severity of AEs/SAEs/AESIs, laboratory parameters, RCL testing and monitoring/reporting for insertional oncogenesis as defined in protocol"}

France

Earliest CTIS Part Ii Submission Date

02-05-2024

Latest Decision Or Authorization Date

21-06-2024

Processing Time Days

50

Number Of Sites

2

Number Of Participants

4

Italy

Earliest CTIS Part Ii Submission Date

02-05-2024

Latest Decision Or Authorization Date

26-06-2024

Processing Time Days

55

Number Of Sites

2

Number Of Participants

4

Netherlands

Earliest CTIS Part Ii Submission Date

02-05-2024

Latest Decision Or Authorization Date

18-06-2024

Processing Time Days

47

Number Of Sites

1

Number Of Participants

6

Spain

Earliest CTIS Part Ii Submission Date

02-05-2024

Latest Decision Or Authorization Date

17-06-2024

Processing Time Days

46

Number Of Sites

2

Number Of Participants

7

Primary sponsor

Full Name

USWM Ct LLC

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

collection and entry of local lab data; other clinical operations responsibilities listed in CTIS

Name

Bioclinica Inc.

Responsibilities

medical imaging; patient-reported outcomes (listed roles in CTIS)

Name

Q Squared Solutions Limited

Responsibilities

Central Lab (Kit supplier, sample storage & management)

Third parties

• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical imaging; patient reported outcomes (two Bioclinica entries with duties including medical imaging and patient reported outcomes)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"collection and entry of local lab data; additionally multiple responsibilities (codes listed in CTIS) for clinical trial operations","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"MINARIS Regenerative Medicine GmbH","duties_or_roles":"QP release sites","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"XEVMPD and other safety/pharmacovigilance duties","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Miltenyi Biotec B.V. & Co. KG","duties_or_roles":"QP release sites","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Evidera Inc.","duties_or_roles":"Conducting and analyzing patient interviews","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"transgene persistence and RCL testing for PK and safety; remaining samples storage","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Central Lab (Kit supplier, sample storage & management) and other central lab functions","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"patient reported outcomes (second Bioclinica entry)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Certara USA Inc.","duties_or_roles":"PK parameters","organisation_type":"Pharmaceutical company"}