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

• ClinicalTrials.gov Identifier: NCT06048705
• Recruitment Status: Terminated
• First Posted: September 21, 2023
• Results First Posted: May 10, 2024
• Last Update Posted: May 10, 2024
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

Tracking Information

• First Submitted Date: September 15, 2023
• First Posted Date: September 21, 2023
• Results First Submitted Date: November 20, 2023
• Results First Posted Date: May 10, 2024
• Last Update Posted Date: May 10, 2024
• Actual Study Start Date: March 9, 2021
• Actual Primary Completion Date: June 8, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 24, 2023)

• Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 28 days ]
  DLT events were graded according to NCI-CTCAE v5.0. DLTs were defined as Grade (Gr) 4 (life-threatening and death) related to GSK3901961 2) Gr 3 (Severe or medically significant) at least possibly related to GSK3901961 and do not resolve to Gr <=1 (or Baseline) within 7 days from the onset of the event 3) Gr >=3 non-infectious pneumonitis not responding to oxygen supplementation and systemic steroid treatment 4) Any Gr 3 cytokine release syndrome (CRS) at least possibly related to GSK3901961 that does not improve to Gr <2 (moderate) toxicity within 7 days with or without dexamethasone 5) Any Gr 4 CRS at least possibly related to study product that does not improve to Gr <=2 (or Baseline) within 7 days 6) Any Gr 3 or greater neurotoxicity that does not resolve to Gr <=2 within 72 hours 7) Any Gr >=3 organ toxicity (exclusive of CRS toxicity) involving major organ systems that persists for >72 hours and occurs within 28 days of infusion.
• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity [ Time Frame: Up to approximately 21 months ]
  An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose can result in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth or is medically significant or requires intervention to prevent one or the outcomes listed above. AEs and SAEs were graded according to NCI-CTCAE v5.0. Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences; Grade 5- Death related to AE. AEs which start or worsen on or after T-cell infusion are classified as treatment emergent. SAEs are subset of AEs. Results for maximum severity grades has been presented.
• Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) [ Time Frame: Up to approximately 21 months ]
  An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. AESIs included events of Cytokine Release Syndrome (CRS), Haematopoietic cytopenias (including pancytopenia and aplastic anaemia), Graft versus Host Disease (GvHD), Immune Effector-Cell Associated Neurotoxicity Syndrome (ICANS), Guillain-Barre Syndrome (GBS), Pneumonitis and treatment-related inflammatory response at tumor site(s) and Neutropenia Grade 4 lasting more than or equal to 28 days. AEs which start or worsen on or after T-cell infusion are classified as treatment emergent.

Original Primary Outcome Measures (submitted: September 15, 2023)

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

Current Secondary Outcome Measures (submitted: November 24, 2023)

• Overall Response Rate (ORR) Assessed by Investigator According to RECIST v1.1 [ Time Frame: Up to approximately 21 months ]
  Overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1 relative to the total number of participants in the analysis population. Partial response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response (CR) was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.
• Duration of Response (DoR) [ Time Frame: Up to approximately 21 months ]
  DoR is defined as the interval of time (in months) from first documented evidence of the confirmed response (PR or CR) as assessed by local investigators to the date of disease progression per RECIST v1.1 or death due to any cause, among participants with a confirmed response of PR or CR. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.
• Maximum Transgene Expansion (Cmax) of GSK3901961 [ Time Frame: Up to 21 days ]
  Cmax was defined as peak cell expansion during the interventional phase. Blood samples were collected to measure Cmax.
• Time to Cmax (Tmax) of GSK3901961 [ Time Frame: Up to 21 days ]
  Tmax was defined as time to peak cell expansion during the interventional phase. Blood samples were collected to measure Tmax.
• Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) [ Time Frame: Up to 28 days ]
  Area under the cell expansion-time curve from first T-cell infusion to Day 28. Blood samples were collected to measure AUC (0-28 days).

Original Secondary Outcome Measures (submitted: September 15, 2023)

• Overall Response Rate (ORR) assessed by investigator according to RECIST v1.1 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: Up to approximately 21 months ]
• Time to Cmax (Tmax) [ Time Frame: Up to approximately 21 months ]
• Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) [ Time Frame: Up to 28 days ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: Assessment of Safety and Recommended Phase 2 Dose of Autologous T Cells Engineered With an Affinity-enhanced TCR Targeting NYESO1 and LAGE1a, and Co-expressing CD8α (GSK3901961) in Participants With NYESO1 and/or LAGE1a Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma / Myxoid/Round Cell Liposarcoma; or NYESO1 and/or LAGE1a Positive Previously Treated Metastatic Non-Small Cell Lung Cancer
• 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 A*02:01, HLA-A*02:05 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.
• Detailed Description: This study is a substudy of the Master record - (209012) NCT04526509.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neoplasms

Intervention

• Drug: GSK3901961
  GSK3901961 was administered.
• Drug: Cyclophosphamide
  Cyclophosphamide was administered as lymphodepleting chemotherapy.
• Drug: Fludarabine
  Fludarabine was administered as lymphodepleting chemotherapy.

Study Arms

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.

Interventions:

• Drug: GSK3901961
• Drug: Cyclophosphamide
• Drug: Fludarabine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: September 15, 2023): 7
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: June 8, 2023
• Actual Primary Completion Date: June 8, 2023 (Final data collection date for primary outcome measure)

Eligibility 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-A*02:01, HLA-A*02:05, 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Germany, Netherlands, Sweden, United States

Administrative Information

• NCT Number: NCT06048705
• Other Study ID Numbers: 209012 Substudy 1
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• URL: http://www.gsk.com/en-gb/innovation/trials/data-transparency/

• Current Responsible Party: GlaxoSmithKline
• Original Responsible Party: Same as current
• Current Study Sponsor: GlaxoSmithKline
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

• PRS Account: GlaxoSmithKline
• Verification Date: November 2023