letetresgene autoleucel (GSK3377794) / Adaptimmune, US WorldMeds - LARVOL DELTA

Safety and efficacy of letetresgene autoleucel alone or with pembrolizumab for relapsed/refractory multiple myeloma. (PubMed, Blood Adv) - P1 | "Two responders, but none of the non-responders, exhibited elevated cytokine levels post lete-cel infusion. Lete-cel had a manageable safety profile consistent with other lete-cel studies and demonstrated clear but transient antitumor activity in patients with RRMM."

Journal • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology • CTAG1B • CTAG2 • HLA-A • IL6

Safety and Tolerability of Letetresgene Autoleucel (Lete-cel; GSK3377794): Pilot Studies in Patients With Advanced Non-Small Cell Lung Cancer. (PubMed, Clin Cancer Res) - "Extensive HLA-A*02 and antigen expression testing was performed to identify potential participants. Lete-cel was generally well tolerated and had no unexpected AEs. Anti-tumor activity was observed in a limited number of patients."

IO biomarker • Journal • Metastases • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Hematological Disorders • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CTAG1B • CTAG2 • HLA-A

Lete-cel in patients with synovial sarcoma or myxoid/round cell liposarcoma: Planned interim analysis of the pivotal IGNYTE-ESO trial. (ASCO 2024) - P2 | "LD (fludarabine 120 mg/m 2 , cyclophosphamide 2700–3600 mg/m 2 , cumulative) was dose reduced for predefined risk factors. IGNYTE-ESO SS2 met the primary endpoint success criterion at this planned IA, with a 40% ORR consistent across SyS and MRCLS, and a known safety profile of hematologic toxicity and CRS. This supports the potential of lete-cel as a novel therapy for pts with advanced or metastatic SyS and MRCLS."

Clinical • Anemia • Hematological Disorders • Leukopenia • Liposarcoma • Neutropenia • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • Thrombocytopenia • CTAG1B

Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma. (PubMed, J Clin Oncol) - P2 | "To our knowledge, this study is the first demonstrating the clinical promise of lete-cel in HLA-/NY-ESO-1-positive patients with advanced MRCLS."

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Hematological Disorders • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • CTAG1B • HLA-A

Primary efficacy and safety of letetresgene autoleucel (lete-cel; GSK3377794) pilot study in patients with advanced and metastatic myxoid/round cell liposarcoma (MRCLS). (ASCO 2022) - P2 | " This is an open label, study of lete-cel in pts with advanced or metastatic MRCLS following reduced-dose (Cohort 1 [C1]; 30 mg/m2 fludarabine [flu] x 3d + 600 mg/m2 cyclophosphamide [cy] x 3d) or standard dose (Cohort 2 [C2]; 30 mg/m2 flu x 4d + 900 mg/m2 cy x 3d) lymphodepletion (LD). Treatment with a single dose of lete-cel showed anti-tumor activity, including response and long median PFS with an acceptable safety profile in pts with advanced and metastatic MRCLS."

Clinical • Graft versus Host Disease • Hematological Disorders • Immunology • Inflammation • Liposarcoma • Neutropenia • Oncology • Sarcoma • Solid Tumor • CTAG1B • HLA-A

Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma (clinicaltrials.gov) - P2 | N=7 | Completed | Sponsor: USWM, LLC (dba US WorldMeds) | Active, not recruiting ➔ Completed | Trial completion date: Jul 2026 ➔ Mar 2026

Trial completion • Trial completion date • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B

Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma or Myxoid/Round Cell Liposarcoma (clinicaltrials.gov) - P2 | N=82 | Completed | Sponsor: USWM CT, LLC | Active, not recruiting ➔ Completed

Trial completion • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • DDIT3 • EWSR1 • FUS • SSX1

IGNYTE-ESO: Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors (clinicaltrials.gov) - P2 | N=103 | Active, not recruiting | Sponsor: USWM CT, LLC | Trial completion date: Jul 2026 ➔ Jul 2028

Trial completion date • Oncology • Solid Tumor • CTAG1B

Efficacy and safety of engineered TCR-T cell therapy (afami-cel, lete-cel) in pediatric synovial sarcoma. (ASCO 2026) - P1, P1/2, P2 | "Engineered TCR-T cell therapy targeting NY-ESO-1 (lete-cel) or MAGE-A4 (afami-cel) has shown responses and durable responses in the pediatric SyS population. The safety profile in this age group is consistent with that observed in the adult population. TCR-T represents a potential new treatment paradigm for pediatric SyS patients."

Clinical • Hematological Disorders • Pediatrics • Rhabdomyosarcoma • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • MAGEA4

The Landscape of Clinical Trials for TCR-T Cell Therapy. (PubMed, Am J Clin Oncol) - "NY-ESO-1 is the most prominent target, followed by MAGE-A4, KRAS, PRAME, HPV16 E6/E7, and HBV surface antigen, with letetresgene autoleucel and LioCyx-M004 being the most investigated TCR-T products. Collectively, TCR-T therapy is a promising field in tumor immunotherapy with continuous research investment and advancing clinical progress."

Journal • Head and Neck Cancer • Hematological Disorders • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CTAG1B • KRAS • MAGEA4 • PRAME

208750/04: Long-Term Follow-Up (LTFU) of Participants Treated with Adoptive Cell Therapies (clinicaltrialsregister.eu) - P1 | N=5 | Recruiting | Sponsor: USWM Ct LLC | N=10 ➔ 5

Enrollment change • Hematological Malignancies • Liposarcoma • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma (clinicaltrials.gov) - P2 | N=7 | Active, not recruiting | Sponsor: USWM, LLC (dba US WorldMeds) | Trial completion date: Jul 2025 ➔ Jul 2026

Trial completion date • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B

Letetresgene autoleucel in advanced non-small cell lung cancer: a step towards truly personalized immunotherapy? (PubMed, Transl Lung Cancer Res) - No abstract available

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma

INTEGRATED EFFICACY AND SAFETY ANALYSIS OF LETETRESGENE AUTOLEUCEL, A T-CELL RECEPTOR T-CELL THERAPY, ACROSS CLINICAL TRIALS OF PATIENTS WITH SYNOVIAL SARCOMA AND MYXOID/ROUND CELL LIPOSARCOMA (CTOS 2025) - No abstract available

Clinical • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Integrated efficacy and safety analysis of letetresgene autoleucel, a T-cell receptor T-cell therapy, across clinical trials of patients with synovial sarcoma and myxoid/round cell liposarcoma (SITC 2025) - P1, P2 | "(Horsham, UK), funded by Adaptimmune.Trial Registration Lete-cel pilot trial in SyS (CT.gov, NCT01343043) Lete-cel pilot trial in MRCLS (CT.gov, NCT02992743) Lete-cel phase 2 IGNYTE-ESO (CT.gov NCT03391778)Ethics Approval This was a secondary analysis of existing clinical trial data and did not require ethical approval. Written informed consent was obtained from participants at the time each trial was conducted.Abstract 320 Table 1View inline•Open as popupIntegrated efficacy analysis outcomes from previously treated patients with SyS or MRCLS who received lete-cel treatment in interventional clinical trials (independent review)"

Clinical • IO biomarker • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B

NY-ESO-1 targeting in non-small cell lung cancer: promise and challenges of letetresgene autoleucel. (PubMed, Transl Lung Cancer Res) - No abstract available

Journal • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • CTAG1B

Adoptive T-Cell Therapy in Sarcomas. (PubMed, Curr Oncol Rep) - "The FDA approval of afamitresgene autoleucel for advanced synovial sarcoma and the breakthrough designation of letetresgene autoleucel for myxoid/round cell liposarcoma signify a major turning point...Tumour infiltrating lymphocyte therapy, including lifileucel, is under investigation with checkpoint inhibitors or oncolytic agents to enhance efficacy and manage toxicity...Challenges include HLA restriction, tumour heterogeneity, and manufacturing complexity. Future strategies involving novel antigens, multi-targeting, and combinatorial regimens could broaden patient eligibility and improve therapeutic outcomes."

Journal • Review • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD276 • CTAG1B • FGFR4 • HER-2 • MAGEA4

US WorldMeds Completes Acquisition of Adaptimmune's Cell-Therapy Portfolio; Ensures Continued Patient Access to Tecelra and Advances Development of lete-cel (PRNewswire) - "US WorldMeds (USWM) reported the successful closing of the previously announced acquisition of Adaptimmune Therapeutics plc's (Adaptimmune) cell–therapy assets-including TECELRA (afamitresgene autoleucel), lete–cel, afami–cel, and uza–cel. The acquisition was first announced on July 28, 2025 and has now been finalized. Under the terms of the Asset Purchase Agreement, USWM paid $55 million in cash at closing and will fund up to an additional $30 million in performance-based milestone payments tied to commercial and regulatory outcomes....Key Highlights: (i) Patient care continuity: TECELRA will remain available to patients without interruption, now under USWM's stewardship; (ii) Future development: USWM plans to bring lete–cel to the U.S. market, with potential regulatory approval anticipated in 2026, and will continue development of uza–cel in collaboration with Galapagos."

Commercial • FDA approval • Liposarcoma • Spindle Cell Sarcoma • Synovial Sarcoma

Adaptimmune Announces Entry into Definitive Agreement for Sale of TECELRA, lete-cel, afami-cel and uza-cel Cell Therapies to US WorldMeds (Adaptimmune Press Release) - "Adaptimmune Therapeutics plc...announced its entry into a definitive agreement for the sale of TECELRA, lete-cel, afami-cel, and uza-cel cell therapies to US WorldMeds. Consummation of the sale is expected to occur before the end of the week....Adaptimmune will retain rights to its preclinical assets including PRAME, CD70, and its allogeneic program; Adaptimmune will restructure to support the transition of these therapies to US WorldMeds and to maximize value from its remaining assets."

Commercial • Spindle Cell Sarcoma • Synovial Sarcoma

Adaptimmune Reports Q1 Financial Results and Provides Business Update (Adaptimmune Press Release) - "TECELRA launch 2025 YTD metrics: 28 ATCs available; 21 patients aphresed; and 14 doses invoiced; $4.0 million Tecelra net sales in Q1 2025....Initiate rolling BLA for lete-cel to treat synovial sarcoma and MRCLS in Q4 2025."

FDA filing • Launch • Sales • Liposarcoma • Sarcoma • Synovial Sarcoma

Safety and Tolerability of Lete-cel in NSCLC-Letter. (PubMed, Clin Cancer Res) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Safety and Tolerability of Lete-cel in NSCLC-Reply. (PubMed, Clin Cancer Res) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Review of Adoptive Cellular Therapies for the Treatment of Sarcoma. (PubMed, Cancers (Basel)) - "Engineered TCRs, particularly those targeting MAGE-A4 and NY-ESO-1, have shown promising clinical results in synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS), leading to the recent FDA approval of afamitresgene autoleucel (afami-cel) and letetresgene autoleucel (lete-cel)...Future research will focus on optimizing lymphodepleting regimens, mitigating toxicity, enhancing in vivo persistence, and combining ACT with other therapeutic agents. As clinical trials expand, ACT holds the potential to revolutionize sarcoma treatment by offering durable, targeted therapies for previously refractory disease."

Journal • Review • Hematological Malignancies • Liposarcoma • Melanoma • Multiple Myeloma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD276 • CTAG1B • HER-2 • MAGEA4

Letetresgene Autoleucel: A Milestone in Treatment of Myxoid/Round Cell Liposarcoma. (PubMed, J Clin Oncol) - No abstract available

Journal • Liposarcoma • Oncology • Sarcoma • Solid Tumor

Adaptimmune Provides Q4 and Full Year 2024 Business Update (Adaptimmune Press Release) - "Lete-cel on track to initiate rolling BLA submission late 2025; approval anticipated 2026...Implemented additional cost reduction for the PRAME and CD70 programs. The Company anticipates this will generate an additional $75m to $100m in aggregate cost savings over the next 4 years."

FDA approval • FDA filing • Pricing • Oncology • Soft Tissue Sarcoma • Synovial Sarcoma