Synovial sarcoma and Myxoid/Round Cell Liposarcoma (MRCLS) MedDRA version: 20.0 Level: PT Classification code 10042863 Term: Synovial sarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10073137 Term: Myxoid liposarcoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Classification code 10073139 Term: Round
Conditions
Interventions
Product Name: GSK3377794
Product Code: GSK3377794
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: N/A
CAS Number: N/A
Current Sponsor code: Letetresgene autoleucel (lete-cel
GSK3377794)
Other descriptive name: NY-ESO-1c259T
Concentration unit: billion organisms billion organisms
Concentration type: range
Concentration number: 1-15
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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. 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 also 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. 3.Participant has a diagnosis of synovial sarcoma or myxoid/ round cell liposarcoma, confirmed by local histopathology with evidence of diseasespecific translocation. Note: Evidence of a relevant disease-specific translocation is required at latest prior to leukapheresis (Inclusion 8). 4. Participant has advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma. Unresectable refers to a tumor lesion in which clear surgical excision margins cannot be obtained without leading to significant functional compromise. 5. Male or female. Contraception requirements will apply at the time of leukapheresis and treatment. 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 GSKsponsored protocol or under another substudy. For guidance on acceptable specimen material see Tumor Biopsies under Section 5.1 Leukapheresis Eligibility Screening -Prior to finalizing participant treatment plan, please note that bridging/standard of care anti-cancer therapy is allowed under Section 7.1.2 conditions but that there are washout requirements prior to leukapheresis and prior to lymphodepletion. Additional considerations should be given to accumulated radiotherapy prior to lymphodepletion.All the Inclusion Criteria from Section 6.1.1 must apply again prior to leukapheresis. In addition, the following criteria must also apply: 7. Life expectancy =24 weeks 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). Note: Methods, such as, but not limited to, fluorescence in situ hybridization (FISH) assay or Next Generation Sequencing (NGS) or Immuno HistoChemistry (IHC) using fusion-specific antibody are commonly used to detect translocations. 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 (metastatic or inoperable) 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. 10.Participant must be positive for HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 alleles by a validated t
Exclusion criteria
Exclusion criteria: 1.Participant has been previously treated for advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma. 2. Central nervous system metastases. 3. Any other prior malignancy that is not in complete remission. Exceptions include: a. completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma (e.g. melanoma in situ, basal cell carcinoma, prostate cancer in-situ, periosteal osteosarcoma) b. previous malignancies that have been definitively treated, and have been in remission for 5 years may be enrolled upon consultation with sponsor Medical Monitor or designee 4. Previous treatment with genetically engineered NY-ESO-1-specific T cells. 5. Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody. 6. Prior gene therapy using an integrating vector. 7. Previous allogeneic hematopoietic stem cell transplant. 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. Leukapheresis Eligibility Screening: Participants are not eligible for leukapharesis if any of the Exclusion criteria from section 6.2.1 apply. Please note in particular that mandatory washout period restrictions must be respected (Table 5) before starting leukapheresis. In addition, participants are not eligible for leukapharesis if any of the following criteria apply: 9.Participant has history of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease (e.g. Crohn's disease, systemic lupus) requiring steroids or other immunosuppressive treatments. 10. Uncontrolled intercurrent illness including, but not limited to: a. Ongoing or active infection (including, but not limited to systemic fungal 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 e. Interstitial lung disease (participants with existing pneumonitis as a result of radiation are not excluded; however, participants cannot be oxygen dependent) 11. Current active liver or biliary disease. 12. QTc >480 msec 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. 14. Pregnant or breastfeeding females (due to risk to fetus or newborn). 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 standard of care lines of therapy are allowed only if guidelines and washout periods are followed. 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 the washout period Investigator in agreement with the Sponsor's Medical Monitor 17. Participant has active infection with HIV, HBV, HCV, EBV, CMV, syphilis, or HTLV as defined in the protocol 18. has known psychiatric or substance abuse d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of NY-ESO-1-Specific (c259) T Cells, alone or in combination with other anti-cancer agents, in HLA-A*02:01, HLAA* 02:05 and/or HLA-A*02:06 participants with NY-ESO-1- and/or LAGE-1a positive solid tumors;Secondary Objective: - To further evaluate the efficacy of NY-ESO-1 Specific (c259) T Cells alone or in combination with other anti-cancer agents in HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 participants with NY-ESO-1 and/or LAGE-1a positive solid tumors - To evaluate the safety and tolerability of NY-ESO- 1 Specific (c259) T Cells alone or in combination with other anti-cancer agents in HLA-A*02:01, HLA-A*02:05 and/or HLA-A* 02:06 participants with NY-ESO-1- and/or LAGE-1a positive solid tumors;Primary end point(s): Overall Response Rate (ORR) per RECIST v1.1 (assessed by investigator for Substudy 1 and assessed by independant review committee for Substudy 2);Timepoint(s) of evaluation of this end point: Up to 5 Years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To further evaluate the efficacy of NY-ESO-1 - Time to Response (TTR) - Duration of Response (DoR) - Disease Control Rate (DCR) - Progression Free Survival (PFS) - Overall Survival (OS) for Substudy 2 To evaluate the safety and tolerability of NYESO-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);Timepoint(s) of evaluation of this end point: Up to 5 Years | — |
Countries
Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed