Study of GSK3845097 in Previously Treated Participants With Advanced Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Terminated

CT.gov ID

NCT05943990

Collaborator

(none)

Enrollment

Locations

Arm

22.1

Actual Duration (Months)

0.2

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To assess the safety, tolerability and determine recommended phase 2 dose (RP2D) of GSK3845097 in HLA-A02:01, HLA-A02:05 and/or HLA-A*02:06 positive participants with New York esophageal squamous cell carcinoma (NY-ESO)-1 and/or Cancer testis antigen 2 (LAGE-1a) positive, previously treated, advanced (metastatic or unresectable) Synovial Sarcoma (SS) and Myxoid/Round Cell Liposarcoma (MRCLS).

Condition or Disease	Intervention/Treatment	Phase
Neoplasms	Drug: GSK3845097 Drug: Cyclophosphamide Drug: Fludarabine	Phase 1

Detailed Description

This study is a substudy of the Master record - (209012) NCT04526509.

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Assessment of Safety and Recommended Phase 2 Dose of Autologous T Cells Engineered With an Affinity-enhanced TCR Targeting NY ESO 1 and LAGE 1a, and Co-expressing the dnTGF-βRII (GSK3845097) in Participants With NY ESO 1 and/or LAGE 1a Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

Actual Study Start Date :

Dec 21, 2020

Actual Primary Completion Date :

Oct 24, 2022

Actual Study Completion Date :

Oct 24, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK3845097 Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive high dose of GSK3845097 after completing lymphodepleting chemotherapy. The first study participant receiving GSK3845097 will receive the total assigned dose as 2 separate infusions 7 days apart, in aliquots of 30% (first infusion) and 70% (second infusion) of the total target dose , respectively. Based on the dose limiting toxicities reported in the first participant, then all subsequent participants treated with GSK3845097 will receive the full dose as a single, i.e., one-time, infusion.	Drug: GSK3845097 GSK3845097 was administered. Drug: Cyclophosphamide Cyclophosphamide was administered as lymphodepleting chemotherapy. Drug: Fludarabine Fludarabine was administered as lymphodepleting chemotherapy.

Arm

Intervention/Treatment

Experimental: GSK3845097

Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive high dose of GSK3845097 after completing lymphodepleting chemotherapy. The first study participant receiving GSK3845097 will receive the total assigned dose as 2 separate infusions 7 days apart, in aliquots of 30% (first infusion) and 70% (second infusion) of the total target dose , respectively. Based on the dose limiting toxicities reported in the first participant, then all subsequent participants treated with GSK3845097 will receive the full dose as a single, i.e., one-time, infusion.

Drug: GSK3845097

GSK3845097 was administered.

Drug: Cyclophosphamide

Cyclophosphamide was administered as lymphodepleting chemotherapy.

Drug: Fludarabine

Fludarabine was administered as lymphodepleting chemotherapy.

Outcome Measures

Primary Outcome Measures

Number of Participants with Dose Limiting Toxicities (DLTs) [Up to approximately 21 months]
Number of Participants with Adverse Events (AEs), Serious AEs and Adverse Events of Special Interest (AESI) based on Severity [Up to approximately 21 months]

Secondary Outcome Measures

Overall Response Rate (ORR) assessed by investigator according to RECIST v1.1 [Up to approximately 21 months]
Overall response rate was defined as the percentage of participants with a confirmed complete response (CR) or a confirmed partial response (PR) relative to the total number of participants within the relevant cohort and analysis population at any time per Response evaluation criteria in solid tumors (RECIST) version 1.1 as determined by the local investigators.
Duration of Response (DoR) [Up to approximately 21 months]
Duration of response was defined as, in the subset of participants who show a confirmed CR or PR as assessed by local investigators, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.
Maximum transgene expansion (Cmax) [Up to approximately 21 months]
Time to Cmax (Tmax) [Up to approximately 21 months]
Area under the concentration time curve from zero to time t AUC(0-t) [Up to approximately 21 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participant must be >=18 years of age and weighs ≥40 kg on the day of signing informed consent
Participant must be positive for HLA-A02:01, HLA-A02:05, and/or HLA-A*02:06 alleles
Participant's tumor must have tested positive for NY-ESO-1 and/or LAGE-1a expression by a GSK designated laboratory
Performance status: Eastern Cooperative Oncology Group of 0-1
Participant must have adequate organ function and blood cell counts 7 days prior to leukapheresis
Participant must have measurable disease according to RECIST v1.1.
Participant has advanced (metastatic or unresectable) SS or MRCLS confirmed by local histopathology with evidence of disease-specific translocation
Participant has completed at least one standard of care (SOC) treatment including anthracycline containing regimen unless intolerant to or ineligible to receive the therapy.
Participants who are not candidates to receive anthracycline should have received ifosfamide unless also intolerant to or ineligible to receive ifosfamide. Participants who received neoadjuvant/adjuvant anthracycline or ifosfamide based therapy and progressed will be eligible

Exclusion Criteria:

Central nervous system (CNS) metastases, with certain exceptions for CNS metastases in NSCLC as specified in the protocol
Any other prior malignancy that is not in complete remission
Clinically significant systemic illness
Prior or active demyelinating disease
History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments
Previous treatment with genetically engineered NY-ESO-1-specific T cells, NY-ESO-1 vaccine or NY-ESO-1 targeting antibody
Prior gene therapy using an integrating vector
Previous allogeneic hematopoietic stem cell transplant within the last 5 years or solid organ transplant
Washout periods for prior radiotherapy and systemic chemotherapy must be followed
Major surgery within 4 weeks prior to lymphodepletion
Pregnant or breastfeeding females

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	New Haven	Connecticut	United States	06504
2	GSK Investigational Site	Jacksonville	Florida	United States	32224
3	GSK Investigational Site	Tampa	Florida	United States	33612
4	GSK Investigational Site	Atlanta	Georgia	United States	30322
5	GSK Investigational Site	Westwood	Kansas	United States	66205
6	GSK Investigational Site	Lexington	Kentucky	United States	40536
7	GSK Investigational Site	Baltimore	Maryland	United States	21287
8	GSK Investigational Site	Saint Louis	Missouri	United States	63110
9	GSK Investigational Site	New York	New York	United States	10032
10	GSK Investigational Site	New York	New York	United States	10065
11	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19111
12	GSK Investigational Site	Houston	Texas	United States	77030
13	GSK Investigational Site	Melbourne	Victoria	Australia	3000
14	GSK Investigational Site	Toronto	Ontario	Canada	M5G 2M9
15	GSK Investigational Site	Montréal	Quebec	Canada	H1T 2M4
16	GSK Investigational Site	Muenchen	Bayern	Germany	81377
17	GSK Investigational Site	Hannover	Niedersachsen	Germany	30625
18	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	50937
19	GSK Investigational Site	Dresden	Sachsen	Germany	01307
20	GSK Investigational Site	Amsterdam		Netherlands	1066 CX
21	GSK Investigational Site	Stockholm		Sweden	SE-171 64