Tecelra (afamitresgene autoleucel) / Adaptimmune - LARVOL DELTA

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

Metastases • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

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

From lactation to tumor immune modulation: emerging roles of prolactin in regulating tumor antigen presentation in breast cancer (IMMUNOLOGY 2025) - "In an in vivo syngeneic mouse model with 4T1 TNBC cells, systemic knockdown of the prolactin receptor (LFPRLR) restored antigen presentation, increasing CD80 expression on dendritic cells and macrophages, reducing PD-L1, and activating CD4+ and CD8+ T cells. Our findings reveal a novel role for prolactin in inhibiting immune cell antigen presentation within the tumor microenvironment, suggesting that targeting PRLR signaling could enhance anti-tumor immunity."

IO biomarker • Breast Cancer • Immune Modulation • Immunology • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD4 • CD8 • CD80 • PD-L1 • PRLR • TAP1

Development of MAGE-A4 IHC 1F9 pharmDx for melanoma-associated antigen 4 (MAGE-A4) detection in FFPE synovial sarcoma specimens for afamitresgene autoleucel therapy (AACR 2025) - "These studies demonstrated high analytical assay performance and observer scoring precision of the MAGE-A4 IHC 1F9 pharmDx assay in SyS and combined with sqNSCLC specimens at MAGE-A4 TIPS (≥ 2+) ≥ 75%."

Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • MAGEA4

Allele-specific HLA LOH frequencies and survival outcomes in cancer: a real-world analysis (AACR 2025) - "For instance, A*02:01-specific LOH was associated with worse survival in CRC (HR 0.5355, 95% CI 0.2991-0.9589), but showed a trend toward improved survival in LUAD (HR 1.342, 95% CI 0.7713-2.336), in all patients treated with any therapy.Our findings highlight that over 90% of cancer cases found in the database are genomically intact at the HLA class I locus, preserving the molecular complex needed for TCR-HLA:driver mutation-based therapies. However, the association of A*02:01-specific LOH with poorer survival in CRC and the opposite trend in LUAD underscores the need for further investigation into allele-specific factors that may influence outcomes across various cancer types, treatment lines, and therapeutic modalities."

Clinical • IO biomarker • Real-world • Real-world evidence • Colorectal Cancer • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • TP53

Nursing Considerations for Cell Therapy With Afamitresgene Autoleucel (Afami-cel) in Patients With Solid Tumors (ONS 2025) - P2 | "Patients then receive intravenous lymphodepleting chemotherapy (fludarabine 30 mg/m2/day on days −7 to −4 and cyclophosphamide 600 mg/m2/day on days −7 to −5) before afami-cel infusion... The Figure shows adverse events of interest occurring in SPEARHEAD-1 and some clinical management recommendations. Nurses should be aware of the symptoms and management of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), which can occur in the ~week after infusion and may be serious. To assist with management, the immune effector cell−associated encephalopathy (ICE) score may be used to grade ICANS, and the Penn, CTCAE, and Lee scales for CRS."

Clinical • IO biomarker • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • HLA-A • MAGEA4

Solid tumour cellular therapy - principles of toxicity management. (PubMed, Immunooncol Technol) - "Extrapolating from experience with CAR T in the field of haemato-oncology, coupled with the historical use of high-dose interleukin-2 in solid tumour therapeutic regimens and more recently lifileucel and afami-cel, has led to the development of core principles for managing toxicity, which is discussed here. Looking to the future, a rapidly developing field with next-generation ACT products, a basic knowledge of such core principles will be an important foundation for healthcare professionals working in this space."

Adverse events • Journal • Review • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Gene and Cell Therapy for Sarcomas: A Review. (PubMed, Cancers (Basel)) - "Rexin-G: the first tumor-targeted gene therapy vector designed to target all advanced solid malignancies, including chemo-refractory osteosarcomas and soft tissue sarcomas, was approved by the Philippine FDA in 2007. Gendicine was the first oncolytic virus approved for intratumoral delivery in China in 2003... The future of gene and cell therapy for sarcomas holds great promise, as research moves to late-stage clinical development. The integration of gene and cell therapies into standard sarcoma treatment protocols has the potential to significantly improve the quality of life and outcomes for patients with this rare and challenging group of cancers."

Journal • Review • Gene Therapies • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma

Expanding the Therapeutic Reach of Chimeric Antigen Receptor T-Cells and Bispecific T-Cell Engagers Across Solid Tumors. (PubMed, JCO Precis Oncol) - "In this review, we discuss the landmark data that led to the commercialization of four novel FDA-approved T-cell-based therapeutics in solid malignancies, including tarlatamab for small cell lung cancer, afamitresgene autoleucel for synovial sarcoma, lifileucel for metastatic melanoma, and tebentafusp for metastatic uveal melanoma...Some solutions include addressing on-target, off-tumor toxicity; improving the manufacturing of CARs; optimizing the tissue-specific tumor microenvironment by combating immune desert tumors; and discovering natural tumor neoantigens and non-self-epitopes generated by tumor-specific mutations. These concepts can help provide transformative benefits for patients with solid malignancies in the coming years."

IO biomarker • Journal • Review • Brain Cancer • Breast Cancer • CNS Tumor • Eye Cancer • Genito-urinary Cancer • Glioblastoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lung Cancer • Lymphoma • Melanoma • Multiple Myeloma • Neuroblastoma • Oncology • Prostate Cancer • Sarcoma • Small Cell Lung Cancer • Solid Tumor • Synovial Sarcoma • Uveal Melanoma • HER-2 • IL13RA2 • PSCA

Afamitresgene autoleucel: first cell therapy for synovial sarcoma. (PubMed, Trends Pharmacol Sci) - No abstract available

Journal • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Adaptimmune Provides Q4 and Full Year 2024 Business Update (Adaptimmune Press Release) - "20 Authorized Treatment Centers (ATCs) now accepting referrals; On track to have the full network of approximately 30 ATCs open by end of 2025."

Commercial • Sarcoma • Spindle Cell Sarcoma

Features of HLA-A*02 in Identifying Eligible Patients for Tecelra TCR-T Therapy. (PubMed, Cancer Sci) - "Using computational tools, the study identifies specific HLA-A*02 alleles, such as HLA-A*02:07, HLA-A*02:05, and others, with low affinity for the GV10 peptide or a risk of inducing alloreactivity. These findings provide insights into patient selection for Tecelra therapy, suggesting exclusion criteria for certain HLA-A*02 subtypes to optimize treatment efficacy and minimize adverse reactions."

Journal • HLA-A • MAGEA4

Tecelra's Approval: A Breakthrough in Synovial Sarcoma Therapy. (PubMed, Curr Drug Discov Technol) - No abstract available

Journal • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

A Review of CAR T Cells and Adoptive T-Cell Therapies in Lymphoid and Solid Organ Malignancies. (PubMed, Med Sci Monit) - "A tumor-infiltrating lymphocyte (TIL) therapy, lifileucel, is FDA-approved for advanced melanoma...The results from ongoing studies and clinical trials are awaited in solid tumors (melanoma, sarcomas, and carcinomas). This article reviews recent developments and ongoing challenges in adoptive T-cell therapies, including CAR T-cell therapies, in lymphoid and solid organ malignancies."

Journal • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Mantle Cell Lymphoma • Melanoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Emerging treatments for sarcoma: from 2024 onward. (PubMed, Expert Opin Emerg Drugs) - "While these strategies have demonstrated some success, the overall improvements in survival have often been modest, irrespective of the therapeutic modality. This underscores critical concerns regarding the true cost-benefit balance and the potential for adverse effects, particularly when evaluated over extended follow-up periods."

Journal • Review • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

Long-Term Survival of Patients with Advanced/Metastatic Synovial Sarcoma or Myxoid/Round Cell Liposarcoma Who Received the T-Cell Receptor T-Cell Therapy, Afamitresgene Autoleucel, in the Phase 2 Spearhead-1 Trial (TCT-ASTCT-CIBMTR 2025) - P2 | "To date, survival of ~3 years after treatment with afami-cel has been observed in 25% of pts with advanced/metastatic SyS or MRCLS in Cohort 1 of SPEARHEAD-1; work is ongoing to delineate potential mechanisms/factors influencing this."

Clinical • IO biomarker • Metastases • P2 data • Hematological Disorders • Liposarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • MAGEA4

FDA Comments - Tecelra (TCT-ASTCT-CIBMTR 2025) - No abstract available

Novel Therapeutics in Soft Tissue Sarcoma. (PubMed, Cancers (Basel)) - "Examples are the tyrosine kinase inhibitors avapritinib and ripretinib in gastrointestinal stromal tumours (GIST), the immune check point inhibitor atezolizumab in alveolar soft part tissue sarcoma, the γ-secretase inhibitor nirogacestat in desmoid tumours, the NTRK inhibitors larotrectinib and entrectinib in tumours with NTRK fusions, the mTOR inhibitor nab-sirolimus in PEComa, and the EZH-2 inhibitor tazemetostat in epithelioid sarcoma...The challenges in drug development in soft tissue sarcoma are due to the rarity and the molecular heterogeneity of the disease and the fact that many subtypes are associated with complex karyotypes or non-targetable molecular alterations. We believe that progress maybe possible with a better understanding of the complex biology, the development of novel compounds for difficult targets such as proteolysis targeting chimeras (Protacs), the utilisation of modern clinical trial designs, and enhanced collaboration of academia with industry..."

Journal • Review • Angiosarcoma • Desmoid Tumors • Gastrointestinal Cancer • Gastrointestinal Disorder • Leiomyosarcoma • Liposarcoma • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Synovial Sarcoma • Targeted Protein Degradation • Undifferentiated Pleomorphic Sarcoma • HLA-A • MAGEA4 • NTRK

SPEARHEAD-1: Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma (clinicaltrials.gov) - P2 | N=52 | Active, not recruiting | Sponsor: Adaptimmune | Recruiting ➔ Active, not recruiting | N=120 ➔ 52

Enrollment change • Enrollment closed • Liposarcoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • HLA-A • MAGEA4

MSK Research Highlights, December 18, 2024 (Memorial Sloan Kettering Cancer Center) - "The first human leukocyte antigen (HLA)-restricted therapies were recently approved by the U.S. Food and Drug Administration (FDA) for certain cancers including the T cell receptor therapies tebentafusp and afami-cel, based on studies led by MSK's Alexander Shoushtari, MD...However, HLA genotyping is not currently assessed in routine next-generation sequencing panels that match patients with precision therapies."

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

First Patient Treated with Adaptimmune's TECELRA (afamitresgene autoleucel) (Adaptimmune Press Release) - "TECELRA is the first engineered cell therapy for a solid tumor cancer approved in the U.S., and the first new therapy option in more than a decade for synovial sarcoma....The patient was treated at Moffitt Cancer Center....In August 2024, the U.S. Food and Drug Administration (FDA) granted accelerated approval of TECELRA for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are HLA-A*02:01P, -A*02:02P, -A*02:03P, or -A*02:06P positive and whose tumor expresses the MAGE-A4 antigen as determined by FDA-approved or cleared companion diagnostic devices."

Launch US • Synovial Sarcoma

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) and the NCCN Drugs & Biologics Compendium (NCCN Compendium) for Soft Tissue Sarcoma, Version 4.2024. (NCCN)

NCCN guideline • Soft Tissue Sarcoma

IMPACT OF AFAMI-CEL ON THE HEALTH STATE OF PATIENTS WITH ADVANCED SYNOVIAL SARCOMA OR MYXOID/ROUND CELL LIPOSARCOMA: COHORT 1 OF SPEARHEAD-1 (CTOS 2024) - P1 | "The patient-reported outcomes in this small dataset suggest that afami-cel can positively impact the health status of patients with advanced SyS or MRCLS, with the clinical responses to afami-cel associated with maintenance or improvement in patients' overall health and quality of life.1. D'Angelo, SP et al. Lancet."

Clinical • Metastases • Liposarcoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • MAGEA4

TRANSLATIONAL ANALYSES REVEAL MECHANISMS OF AFAMI-CEL'S ANTI-TUMOR ACTIVITY IN SYNOVIAL SARCOMA (CTOS 2024) - No abstract available

Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma