Tecelra (afamitresgene autoleucel) / Adaptimmune, US WorldMeds - LARVOL DELTA

FINAL ANALYSIS FROM SPEARHEAD-1 COHORT 1 OF AFAMITRESGENE AUTOLEUCEL (“AFAMI-CEL” [FORMERLY ADP-A2M4]) IN ADVANCED SYNOVIAL SARCOMA AND MYXOID/ROUND CELL LIPOSARCOMA (CTOS 2022) - No abstract available

Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Autologous T cell therapy for MAGE-A4 solid cancers in HLA-A*02 patients: a phase 1 trial. (PubMed, Nat Med) - P1 | "In addition, afami-cel has an acceptable benefit-risk profile, with early and durable responses, especially in patients with metastatic SS. Although the small trial size limits conclusions that can be drawn, the results warrant further testing in larger studies."

Journal • P1 data • Head and Neck Cancer • Hematological Disorders • Inflammation • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • HLA-A • IFNG • MAGEA4

Afamitresgene autoleucel for advanced synovial sarcoma and myxoid round cell liposarcoma (SPEARHEAD-1): an international, open-label, phase 2 trial. (PubMed, Lancet) - P1, P2 | "Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies."

Journal • Metastases • P2 data • Hematological Disorders • Leukopenia • Liposarcoma • Neutropenia • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • HLA-A • MAGEA4

Cell therapy in sarcoma: current landscape and future directions. (PubMed, J Immunother Cancer) - "This constituted only the second approval of a cell therapy in a solid tumor following lifileucel in melanoma and demonstrated the potential of cell therapies in sarcomas...However, the broader application of these therapies is hindered by the lack of targetable sarcoma-restricted immunogenic epitopes, spatiotemporal intratumoral heterogeneity, and a profoundly immunosuppressive tumor microenvironment that impedes effector-cell trafficking, expansion and persistence. While cell therapies hold promise for integration into precision medicine approaches for sarcomas, their successful implementation will require careful evaluation of clinical feasibility, logistical considerations and cost-effectiveness to optimize patient outcomes."

Journal • Review • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • MAGEA4

CRISPR-Cas editing technologies for viral-mediated gene therapies of human diseases: Mechanisms, progress, and challenges. (PubMed, Mol Ther Nucleic Acids) - "Since then, the US FDA has approved nearly 30 new viral gene therapy programs, with notable examples including Zolgensma, Spinraza, Hemgenix, Zynteglo, Lyfgenia, Kymriah, Skysona, and Tecelra...In this review, we examine the range of these therapeutics and their viral carriers, focusing primarily on LVs and AAVs. We provide a snapshot of the current status of the field and highlight some of the current challenges in the clinical application of gene therapy, with particular emphasis on viral CRISPR-Cas-based technologies and their future potential."

Journal • Review • Gene Therapies • Genetic Disorders

AN EVALUATION OF AFAMITRESGENE AUTOLEUCEL FOR THE TREATMENT OF ADVANCED SYNOVIAL SARCOMA AND MYXOID ROUND CELL LIPOSARCOMA. (PubMed, Expert Rev Anticancer Ther) - "However, challenges remain regarding HLA restriction, tumor microenvironment resistance, manufacturing delays and cost. Future efforts should focus on broadening applicability, optimizing combinations, and ensuring equitable access."

Journal • Review • Hematological Disorders • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • MAGEA4

Update on pediatric soft tissue sarcomas. (PubMed, Curr Opin Pediatr) - "Pediatric STS are rare and biologically heterogeneous. Genomic advances have refined risk stratification and uncovered therapeutic targets; further progress relies on international collaboration and trials."

IO biomarker • Journal • Review • Alveolar Soft Tissue Sarcoma • Oncology • Pediatrics • Rhabdomyosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • FOXO1 • MYOD1 • NTRK • TP53

A PHASE II STUDY OF HIGH DOSE IFOSFAMIDE IN METASTATIC/LOCALLY ADVANCED SYNOVIAL SARCOMA FROM A TERTIARY CARE CENTER IN INDIA (CTOS 2025) - "Others treatment options like Anlotinib and cellular therapies like afamitresgene autoleucel are either expensive or not suitable due to very low positivity of HLA-02 in Indian populationAs Indian and international data is lacking, we are doing this phase II study and analyse the effectiveness of this drug in this particular sarcoma type.Primary objective: • To study single agent ifosfamide in relapsed metastatic synovial sarcoma patients as determined by overall response rate (Complete response + Partial Response)Secondary objectives include overall survival, Toxity profiles, Quality of life analysis and median progression free survival Study design: Single arm, Phase II, Simon 2-stage clinical trial Study setting: The study will be conducted at Department of Medical Oncology, BRAIRCH, AIIMS, New Delhi... N/A"

Metastases • P2 data • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

THE PATTERN.ORG SARCOMA CONSORTIUM: BUILDING A MULTI-INSTITUTIONAL DATA RESOURCE FOR THE SARCOMA RESEARCH COMMUNITY (CTOS 2025) - "Molecularly focused research has led to breakthroughs, notably afami-cel in synovial sarcoma and nab-sirolimus in PEComa... This pilot sarcoma data consortium project combined efforts from RCRF, UNC and PICI. These data offer some preliminary insights into the cohort, but we seek additional partners to facilitate a multi-institutional consortium around sarcoma sample and data collection and sharing. We plan to bring additional institutions in as we expand this resource in the coming year."

Clinical • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTLA4 • PD-1

SINGLE-CELL RNA SEQUENCING OF AFAMITRESGENE AUTOLEUCEL INDICATES MECHANISMS OF PERSISTENCE AND ANTI-TUMOR ACTIVITY (CTOS 2025) - "We hypothesize that MP with T-cell subsets poised for sustained effector function and long-lived memory formation are capable of longer post-infusion persistence, sustaining higher afami-cel pharmacokinetic exposure, and will discuss the gene expression programs underlying these different cellular potentials."

IO biomarker • Liposarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD4 • MAGEA4

Preclinical Proof of Concept for Decentralized Manufacturing of a MAGE-A4/CD8alpha-Expressing Autologous T-Cell Therapy for Solid Tumors (ASH 2024) - P1, P2 | "We investigated suitability of a decentralized, rapid, and fresh cell manufacturing platform to produce T cells expressing the MAGE-A4 TCR and CD8α co-receptor compared with the established central manufacturing process for uza-cel. Importantly, the GDM platform could significantly reduce total vein-to-vein time for eligible patients from several weeks to ~1 week. The GDM system will be used to supply MAGE-A4/CD8α–expressing T cells for a proof-of-concept clinical trial to assess their safety and efficacy in patients with advanced head and neck cancer."

IO biomarker • Preclinical • Genito-urinary Cancer • Head and Neck Cancer • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • Urothelial Cancer • CD4 • IFNG • MAGEA4

Discovery and validation of DARKFOXTM, a novel alternative open reading frame of FOXM1 that is an attractive cancer antigen for peptide-HLA targeting immunotherapy (SITC 2025) - "Background Targeted immunotherapies are a highly promising treatment strategy for solid tumors, exemplified by the recent FDA approvals of tebentafusp and afamitresgene autoleucel, which target Class I peptide-HLA (pHLA) antigens...It is characterised by minimal presence in normal tissues, homogeneous intratumoral expression, and robust presentation by HLA on the surface of tumor cells. ENA101, an EnTiCE® bispecific T-cell engager targeting DARKFOX-A3, is currently in IND-enabling studies."

IO biomarker • Esophageal Adenocarcinoma • Esophageal Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOXM1

Single-cell RNA sequencing of afamitresgene autoleucel indicates mechanisms of persistence and anti-tumor activity (SITC 2025) - P2 | "(Glasgow, UK) funded by Adaptimmune. The authors would like to thank the patients, their families, caregivers, and the teams involved in the SPEARHEAD-1 trial.Trial Registration SPEARHEAD-1 is registered at ClinicalTrials.gov with ID NCT04044768.Ethics Approval SPEARHEAD-1 was approved by local or independent institutional review boards or ethics committees at each participating site and all patients provided written informed consent."

IO biomarker • Liposarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD4 • MAGEA4

Discovery and validation of DARKFOXTM, a novel alternative open reading frame of FOXM1 that is an attractive cancer antigen for peptide-HLA targeting immunotherapy (SITC 2025) - "Background Targeted immunotherapies are a highly promising treatment strategy for solid tumors, exemplified by the recent FDA approvals of tebentafusp and afamitresgene autoleucel, which target Class I peptide-HLA (pHLA) antigens...It is characterised by minimal presence in normal tissues, homogeneous intratumoral expression, and robust presentation by HLA on the surface of tumor cells. ENA101, an EnTiCE® bispecific T-cell engager targeting DARKFOX-A3, is currently in IND-enabling studies."

IO biomarker • Esophageal Adenocarcinoma • Esophageal Cancer • Oncology • Ovarian Cancer • Solid Tumor • FOXM1

Current progress and latest therapeutic options in immuno-oncology (PubMed, Dtsch Med Wochenschr) - "For solid cancers, these comprise the antibody-drug-conjugate Mirvetuximab Soravtansine for platinum-resistant ovarian cancer, the monoclonal antibody Zolbetuximab for Claudin-18.2 positive gastric adenocarcinoma and the checkpoint inhibitor Tislelizumab for esophageal squamous cell carcinoma. For the treatment of relapsed or refractory hematologic B cell malignancies, the use of bispecific T cell engaging antibodies like the BCMA-CD3 targeting Teclistamab and CD20-CD3 targeting Glofitamab were approved by the EMA recently.Combinatorial approaches of conventional chemotherapy and checkpoint inhibitors for the treatment of cholangiocarcinoma, urothelial carcinoma and endometrial carcinoma received recent approval.A CD38 antibody-based bridging therapy for the treatment of newly diagnosed multiple myeloma and the Glofitamab-based approach in combination with Gemcitabine and Oxaliplatin for relapsed DLBCL are the latest additions for hematologic malignancies after promising..."

Journal • Review • Biliary Cancer • Cholangiocarcinoma • Diffuse Large B Cell Lymphoma • Endometrial Cancer • Esophageal Cancer • Esophageal Squamous Cell Carcinoma • Gastric Adenocarcinoma • Gastric Cancer • Hematological Disorders • Hematological Malignancies • Melanoma • Multiple Myeloma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Squamous Cell Carcinoma • Synovial Sarcoma • Urothelial Cancer • CLDN18

Advancing human leukocyte antigen-based cancer immunotherapy: from personalized to broad-spectrum strategies for genetically heterogeneous populations. (PubMed, Trends Cancer) - "Human leukocyte antigen (HLA)-based immunotherapeutics, such as tebentafusp-tebn and afamitresgene autoleucel, have expanded the treatment options for HLA-A*02-positive patients with rare solid tumors such as uveal melanoma, synovial sarcoma, and myxoid liposarcoma...Last, we emphasize the urgent need for further research to better understand HLA allotype heterogeneity and its influence on tumor immunopeptidome-driven immune responses. We anticipate that these strategies will accelerate the development and implementation of both personalized and broad-spectrum HLA-based immunotherapies, and will ultimately improve cancer treatment across genetically heterogeneous patient populations worldwide."

Heterogeneity • Journal • Review • Eye Cancer • Liposarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • Uveal Melanoma • HLA-A

Future Directions and Priorities for Cellular Therapy in Sarcoma: A Report from the Strategic Advances in Sarcoma Science Cell Therapy Breakout. (PubMed, Cancers (Basel)) - "Sarcomas are promising targets for adoptive cell therapy (ACT), as shown by afami-cel's success in synovial sarcoma, but broader impact requires new target discovery, optimal cell selection, improved conditioning, combination treatments, deeper tumor microenvironment understanding, and predictive biomarkers to achieve more durable responses for more patients."

IO biomarker • Journal • Review • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • MAGEA4

Clinical Utility of the Companion Diagnostic and Clinical Trial MAGE-A4 Expression Assays in Identifying Adults With Advanced Synovial Sarcoma for Treatment With Afamitresgene Autoleucel (CAP 2025) - P2 | "Despite being slightly more selective than the CTA, the MAGE-A4 CDxA demonstrated similar clinical utility to the CTA in selecting patients with MAGE-A4–positive SyS who may be eligible for afami-cel. Efficacy Results for Patients With Synovial Sarcoma in SPEARHEAD-1 Based on MAGE-A4 CDxA/CTA Status All authors are shareholders of Adaptimmune. Wang discloses that Adaptimmune sponsored Agilent development of the MAGE-A4 IHC 1F9 PharmDx."

Clinical • Companion diagnostic • IO biomarker • IO Companion diagnostic • Metastases • Melanoma • Sarcoma • Solid Tumor • Synovial Sarcoma • MAGEA4

Adaptimmune Reports Q2 Financial Results and Provides Business Update (Adaptimmune Press Release) - "Q2 Tecelra sales of $11.1m with 16 patients invoiced represents >150% growth vs Q1 2025."

Sales • Soft Tissue Sarcoma • Spindle Cell Sarcoma • Synovial Sarcoma

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

Top advances of the year: Sarcoma. (PubMed, Cancer) - No abstract available

Journal • Oncology • Sarcoma • Solid Tumor

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

New frontier of gene therapy: Tecelra's promise for metastatic synovial sarcoma. (PubMed, J Pak Med Assoc) - No abstract available

Journal • Gene Therapies • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Development of Afami-Cel–Engineered Cell Therapy for Advanced Synovial Sarcoma (ASCO 2025) - No abstract available

Metastases • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma