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

NCT05943990 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 209012 Substudy 22019-004446-14
• Study Type: interventional
• Target: 5
• Locations: 6 countries
• Sites: 21

Brief Summary

To assess the safety, tolerability and determine recommended phase 2 dose (RP2D) of GSK3845097 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, advanced (metastatic or unresectable) Synovial Sarcoma (SS) and Myxoid/Round Cell Liposarcoma (MRCLS).

Conditions

Neoplasms

Keywords

Adoptive T-cell therapy; Advanced synovial sarcoma; Advanced Myxoid/Round Cell Liposarcoma; Advanced tumors; GSK3845097; T cell receptor; Leukapheresis

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  DLT events were graded according to NCI-CTCAE v5.0. DLTs were defined as Grade (Gr) 4 (life-threatening and death) related to GSK3845097 2) Gr 3 (Severe or medically significant) at least possibly related to GSK3845097 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 GSK3845097 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.

  Up to 28 days

• Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity

  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.

  Up to approximately 21 months

• Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI)

  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.

  Up to approximately 21 months

Secondary Outcomes (5)

• Overall Response Rate (ORR) Assessed by Investigator According to RECIST v1.1

  Up to approximately 21 months

• Duration of Response (DoR)

  Up to approximately 21 months

• Maximum Transgene Expansion (Cmax) of GSK3845097

  Up to 21 days

• Time to Cmax (Tmax) of GSK3845097

  Up to 21 days

• Area Under the Time Curve From Zero to Time 28 Days (AUC[0-28])

  Up to 28 days

Study Arms (1)

GSK3845097

EXPERIMENTAL

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; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

GSK3845097 DRUG

GSK3845097 was administered.

GSK3845097

Cyclophosphamide DRUG

Cyclophosphamide was administered as lymphodepleting chemotherapy.

GSK3845097

Fludarabine DRUG

Fludarabine was administered as lymphodepleting chemotherapy.

GSK3845097

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Adaptimmune: lead

Study Sites (21)

GSK Investigational Site

New Haven, Connecticut, 06504, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32224, United States

Location

GSK Investigational Site

Tampa, Florida, 33612, United States

Location

GSK Investigational Site

Atlanta, Georgia, 30322, United States

Location

GSK Investigational Site

Westwood, Kansas, 66205, United States

Location

GSK Investigational Site

Lexington, Kentucky, 40536, United States

Location

GSK Investigational Site

Baltimore, Maryland, 21287, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

New York, New York, 10032, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19111, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

GSK Investigational Site

Melbourne, Victoria, 3000, Australia

Location

GSK Investigational Site

Toronto, Ontario, M5G 2M9, Canada

Location

GSK Investigational Site

Montreal, Quebec, H1T 2M4, Canada

Location

GSK Investigational Site

Munich, Bavaria, 81377, Germany

Location

GSK Investigational Site

Hanover, Lower Saxony, 30625, Germany

Location

GSK Investigational Site

Cologne, North Rhine-Westphalia, 50937, Germany

Location

GSK Investigational Site

Dresden, Saxony, 01307, Germany

Location

GSK Investigational Site

Amsterdam, 1066 CX, Netherlands

Location

GSK Investigational Site

Stockholm, SE-171 64, Sweden

Location

MeSH Terms

Conditions

Neoplasms; Liposarcoma, Myxoid

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Liposarcoma; Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• Adaptimmune Patient Enquiries

  Adaptimmune

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2023
• First Posted: July 13, 2023
• Study Start: December 21, 2020
• Primary Completion: October 24, 2022
• Study Completion: October 24, 2022
• Last Updated: November 13, 2024
• Results First Posted: March 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

CA (2); AU (1); NL (1); DE (4); US (12); SE (1)