Study of GSK3901961 In Previously Treated Advanced (Metastatic OR Unresectable) Synovial Sarcoma/ Myxoid/Round Cell Liposarcoma, and Previously Treated Metastatic Non-Small Cell Lung Cancer
Study Details
Study Description
Brief Summary
The primary purpose of this sub study is to assess the safety, tolerability and determine recommended Phase 2 dose (RP2D) of GSK3901961 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 metastatic Non-Small Cell Lung Cancer (NSCLC) and previously treated, advanced (metastatic or unresectable) Synovial Sarcoma/ Myxoid/Round Cell Liposarcoma SS/MRCLS.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
Detailed Description
This study is a substudy of the Master record - (209012) NCT04526509.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: GSK3901961 Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive high dose of GSK3901961 after completing lymphodepleting chemotherapy. The first study participant receiving GSK3901961 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 GSK3901961 will receive the full dose as a single, i.e., one-time, infusion. |
Drug: GSK3901961
GSK3901961 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 Time Curve From Zero to Time 28 Days AUC(0-28) [Up to 28 days]
Eligibility Criteria
Criteria
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
-
Participant has histologically or cytologically confirmed Stage IV NSCLC
-
Participant has been previously treated with SOC for Stage IV NSCLC
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 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 209012 Substudy 1