A study of NY-ESO-1 T-cells (GSK3377794) in synovial sarcoma and myxoid/round cell liposarcoma patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Uswm Ct Llc

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

21 Apr 2020 → ongoing

Decision date (initial)

2024-06-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

USWM CT, LLC

External identifiers

EU CT number

2024-513032-14-00

EudraCT number

2019-000415-87

ClinicalTrials.gov

NCT03967223

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic, Others

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, HLA A*02:05 and/or HLA A*02:06 participants with NY ESO 1 and/or LAGE-1a positive solid tumors

Secondary objectives 2

1. 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.
2. 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

Conditions and MedDRA coding

Synovial sarcoma and Myxoid/Round Cell Liposarcoma (MRCLS)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 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. 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.
3. 3.Participant has a diagnosis of synovial sarcoma or myxoid/ round cell liposarcoma, confirmed by local histopathology and with evidence of disease-specific translocation
4. 4. Participant has advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma.
5. 5. Male or female. Contraception requirements will apply at the time of leukapheresis and treatment.
6. 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.
7. 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:
8. 7. Life expectancy ≥24 weeks
9. 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).
10. 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.
11. 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.
12. 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.
13. 12. Left ventricular ejection fraction ≥45% with no evidence of clinically significant pericardial effusion.
14. 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.
15. 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.
16. For a detailed list of Inclusion Criteria, please refer to the protocol Page No. 173-178

Exclusion criteria 26

1. 1.Participant has been previously treated for advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma.
2. 2. Central nervous system metastases.
3. 3. Any other prior malignancy that is not in complete remission.
4. 4. Previous treatment with genetically engineered NY-ESO-1-specific T cells.
5. 5. Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.
6. 6. Prior gene therapy using an integrating vector.
7. 7. Previous allogeneic hematopoietic stem cell transplant.
8. 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.
9. 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:
10. 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.
11. 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
12. 11. Current active liver or biliary disease.
13. 12. QTc >480 msec
14. 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.
15. 14. Pregnant or breastfeeding females
16. 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.
17. 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.
18. 17. Participant has active infection with HIV, HBV, HCV, EBV, CMV, syphilis, or HTLV as defined in the protocol
19. 18. Has known psychiatric or substance abuse disorders that would interfere with cooperating with study requirements.
20. 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:
21. 19. Participant has received cytotoxic therapy within 3 weeks prior to lymphodepleting chemotherapy.
22. 20. Systemic corticosteroids or any other immunosuppressive therapy within 2 weeks prior to lymphodepleting chemotherapy.
23. 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.
24. 22. All of the participant's measurable lesions have been irradiated within 3 months prior to lymphodepletion.
25. 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.
26. For a detailed list of Exclusion Criteria, please refer to protocol pages 178-182.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Response Rate (ORR) per RECIST v1.1

Secondary endpoints 2

1. To evaluate efficacy of NY-ESO -1 ∙ Time to Response (TTR) ∙ Duration of Response (DoR) ∙ Disease Control Rate (DCR) ∙ Progression Free Survival (PFS)
2. 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)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Uswm Ct Llc

Sponsor organisation

USWM Ct LLC

Address

4441 Springdale Road

City

Louisville

Postcode

40241-1086

Country

United States

Scientific contact point

Organisation

USWM Ct LLC

Contact name

Regulatory Affairs

Public contact point

Organisation

USWM Ct LLC

Contact name

Regulatory Affairs

Third parties 11

Locations

4 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications