anzutresgene autoleucel (IMA203) / Immatics - LARVOL DELTA

Reactivation of Tebentafusp-Induced Skin Toxicity Following PRAME-Specific TCR-T Cell Therapy in Uveal Melanoma (DGHO 2025) - "We report a case of reactivated skin toxicity following PRAME-specific TCR-T therapy in a uveal melanoma patient previously treated with Tebentafusp.A 65-year-old male with metastatic uveal melanoma, refractory to multiple treatments including Tebentafusp, received an IMA203 TCR-T-cell product within compassionate use. This case highlights the importance of considering prior immune-related toxicities when managing solid tumor patients undergoing cellular therapies. Ongoing deep immunophenotyping of peripheral blood via spectral flow cytometry will be presented to further elucidate immune dynamics underlying both therapeutic response and immune-mediated toxicity"

IO biomarker • Dermatology • Eye Cancer • Immunology • Melanoma • Pruritus • Solid Tumor • Uveal Melanoma • PRAME

A Case Series of TCR-T-cell therapy targeting PRAME in combination with BRAF-/MEK-inhibition in three melanoma patients with active CNS metastases (DGHO 2025) - "Low grade CRS and ICANS were successfully treated with tocilizumab and high-dose dexamethasone. Here we show that application of IMA203 or IMA203CD8 TCR-T cells in three heavily pretreated melanoma patients with active CNS metastases and combination with MAPKi was safe with clinically manageable side effects. Additionally, regression of the tumor occurred following TCR-T treatment and although individual contribution of MAPKi and TCR-T cells to the observed CNS responses cannot ultimately be distinguished, CNS activity of IMA203 and IMA203CD8 seems likely given due to disease progression under previous MAPKi treatment."

Clinical • Combination therapy • IO biomarker • Melanoma • Solid Tumor • PRAME

SUPRAME: A Phase 3 trial evaluating IMA203 PRAME-directed TCR T-cell therapy vs investigator's choice in previously treated advanced cutaneous melanoma (SITC 2025) - P1/2, P3 | "Patients in the control arm will receive nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (US), or chemotherapy. The trial is currently enrolling patients in the US and Germany and plans to enroll patients in France, the Netherlands, Canada, and the United Kingdom.Acknowledgements Study funding provided by Immatics US, Inc.Trial Registration NCT06743126Ethics Approval The protocol and all amendments were approved by the appropriate institutional review board or independent ethics committee at each participating study site. The study is being conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines."

IO biomarker • Metastases • P3 data • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • HLA-A • PRAME

A first-in-human, phase 1 trial of IMA203 PRAME-directed TCR T-cell therapy with PRAME-encoding mRNA-4203 in previously treated, unresectable or metastatic cutaneous melanoma or synovial sarcoma (SITC 2025) - P1, P1/2 | "Patients undergo lymphodepletion with cyclophosphamide (500 mg/m2 and fludarabine 30 mg/m2 x 4 days), followed by a one-time infusion of IMA203 and low-dose IL-2 given subcutaneously x10 days. and Moderna Inc.Trial Registration NCT06946225Ethics Approval The protocol and all amendments were approved by the appropriate institutional review board or independent ethics committee at each participating study site. The study is being conducted in accordance with the principles of the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines."

First-in-human • IO biomarker • Metastases • P1 data • Cutaneous Melanoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • HLA-A • PRAME

Quality of starting material result in high manufacturability and favorable product phenotype of IMA203, a PRAME-directed TCR T-cell therapy (SITC 2025) - P1/2 | "Notably, IMA203 manufacturing achieved a 95% success rate at the RP2D (1-10x109 TCR T cells).1 Furthermore, the process consistently yielded final IMA203 product with enriched effector memory and co-stimulatory profiles, reflecting both phenotypic fitness and process robustness. This supports the importance of an optimized TCR T-cell product manufacturing process alongside quality starting material, thereby achieving a high success rate, and promising clinical activity.Acknowledgements Study funding provided by Immatics US, Inc.Trial Registration NCT03686124"

IO biomarker • Melanoma • Oncology • Solid Tumor • B3GAT1 • CD27 • CD28 • CD8 • HLA-A • PD-1 • PRAME • SELL

SUPRAME: A phase III trial evaluating IMA203 T-cell receptor (TCR) T-cell therapy vs investigator's choice in previously treated advanced cutaneous melanoma (ESMO 2025) - P1/2, P3 | "Pts in the control arm will receive nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (US), or chemotherapy. Legal entity responsible for the study Immatics GmbH. Funding Immatics GmbH."

IO biomarker • Metastases • P3 data • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • HLA-A • PRAME

Efficacy and safety of IMA203, a PRAME-directed T-cell receptor (TCR) T-cell therapy, in patients with previously treated advanced or metastatic uveal melanoma from a phase I trial (ESMO 2025) - P1/2 | "UM with prior tebentafusp, measurable disease (RECIST 1.1) and ECOG PS 0-1. Tolerability was favorable. Further study in a larger UM cohort is warranted and planned."

Clinical • IO biomarker • Metastases • P1 data • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • HLA-A • PRAME

Immatics Highlights Compelling Anti-Tumor Activity of Anzu-cel PRAME Cell Therapy in Metastatic Uveal Melanoma at the ESMO 2025 Presidential Symposium (GlobeNewswire) - "As of September 24, 2025, 16 patients with metastatic uveal melanoma were administered a one-time infusion of anzu-cel....Confirmed objective response rate (cORR) of 67% (10/151). Disease control rate (DCR) of 88% (14/16). Median duration of response (mDOR) of 11 months (min 4.4, max 31.6 months). Median progression-free survival (mPFS) of 8.5 months (min 1.4, max 32.9) at a mFU of 10.4 months. The PFS rate was 69% at six months and 39% at 12 months."

P1 data • Uveal Melanoma

Development Path for Anzu-cel in Metastatic Uveal Melanoma (GlobeNewswire) - "Based on the promising clinical data in patients with metastatic uveal melanoma, Immatics has initiated a Phase 2 cohort with approximately 30 uveal melanoma patients planned. The cohort is being conducted at select centers in the U.S. and Germany with deep expertise in uveal melanoma. Given the high prevalence of PRAME expression in uveal melanoma, prospective PRAME testing is no longer required for inclusion in the clinical trial."

Trial status • Uveal Melanoma

Phase 1 study update on IMA203, an autologous TCR T cell therapy against PRAME in patients with PD1-refractory metastatic melanoma (ADO 2025) - No abstract available

Clinical • Metastases • P1 data • Melanoma • Solid Tumor • PD-1 • PRAME

ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors (clinicaltrials.gov) - P1/2 | N=375 | Recruiting | Sponsor: Immatics US, Inc. | Phase classification: P1 ➔ P1/2 | Trial completion date: Dec 2028 ➔ Jun 2032

Monotherapy • Phase classification • Trial completion date • Breast Cancer • Melanoma • Oncology • Solid Tumor • Triple Negative Breast Cancer

ACTengine® IMA203 Combined With mRNA-4203 (clinicaltrials.gov) - P1 | N=15 | Recruiting | Sponsor: Immatics US, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cutaneous Melanoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

SUPRAME: a Phase 3 study of IMA203, a modified TCR T-cell therapy, versus investigator-choice therapy in previously treated patients with advanced cutaneous melanoma (ADO 2025) - No abstract available

Clinical • Metastases • P3 data • Cutaneous Melanoma • Melanoma • Solid Tumor

ACTengine® IMA203 Combined With mRNA-4203 (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Immatics US, Inc. | Initiation date: May 2025 ➔ Aug 2025

Trial initiation date • Cutaneous Melanoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Phase 1 clinical update of IMA203, an autologous TCR-T targeting PRAME in patients with PD1 refractory metastatic melanoma. (ASCO 2025) - P1, P3 | "IMA203 TCR-T was well tolerated and showed durable objective responses in patients with advanced melanoma. Given its promising risk/benefit profile and high PRAME prevalence in melanoma, a registration-directed Phase 3 trial (SUPRAME; NCT06743126) is underway to further evaluate its efficacy in patients with previously treated (2L) advanced cutaneous melanoma."

Clinical • Metastases • P1 data • Cutaneous Melanoma • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • HLA-A • PD-1 • PRAME

SUPRAME: A phase 3 trial comparing IMA203, an engineered T-cell receptor expressing T cell therapy (TCR-T) vs investigator's choice in patients with previously treated advanced cutaneous melanoma. (ASCO 2025) - P3 | "Following lymphodepletion with cyclophosphamide (500 mg/m2 x 4 days) and fludarabine (30 mg/m2 x 4 days), 1-10x109 IMA203 TCR-T cells will be administered, followed by low-dose IL-2 (1mio IU daily x5 days, twice daily x5 days). Patients in the control arm will receive approved investigator's choice of standard treatment (nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (US), chemotherapy)...Secondary endpoints include OS, ORR, safety and patient-reported outcomes (EORTC QLQ-C30, EQ-5D-5L). The trial will enroll patients in the US and Europe."

Clinical • IO biomarker • Metastases • P3 data • Cutaneous Melanoma • Eye Cancer • Melanoma • Oncology • Solid Tumor • Uveal Melanoma • BRAF • HLA-A • PRAME

Trial-in-Progress Poster Summary – IMA203 SUPRAME Phase 3 Trial (GlobeNewswire) - "Based on the positive clinical data and supported by the FDA RMAT designation, Immatics advanced its PRAME cell therapy, IMA203, into the randomized-controlled Phase 3 SUPRAME trial...SUPRAME is planned to be conducted in more than 50 sites in North America and Europe....Patient enrollment and randomization for the trial was initiated in early 2025 and is expected to be completed in 2026....A pre-specified interim data analysis will be triggered upon the occurrence of a defined number of events for PFS (progressive disease or death), anticipated to occur after approximately 200 patients. Immatics aims to submit a Biologics License Application (BLA) to the FDA in 1Q 2027 for full approval."

FDA filing • Trial status • Cutaneous Melanoma

Immatics IMA203 PRAME Cell Therapy Data Presented at 2025 ASCO Annual Meeting Continues to Show Strong Anti-tumor Activity and Durability in Patients with Metastatic Melanoma (GlobeNewswire) - P1b | N=476 | ACTengine (NCT03686124) | Sponsor: Immatics US, Inc. | "Extended Phase 1b trial follow-up on IMA203 PRAME cell therapy in 33 heavily pretreated patients with metastatic melanoma demonstrates favorable tolerability and promising clinical activity with ongoing deep and durable objective responses up to >2.5 years; IMA203 PRAME cell therapy one-time infusion in all melanoma patients shows cORR of 56%; mDOR of 12.1 months at mFU of 13.4 months; mPFS of 6.1 months; mOS of 15.9 months: Cutaneous melanoma subgroup post-checkpoint inhibitor shows cORR of 50%, mDOR not reached at mFU of 16.7 months; mPFS of 6.0 months....Uveal melanoma subgroup, including tebentafusp-refractory patients shows cORR of 67%, mDOR of 11.0 months at mFU of 13.4 months; mPFS of 8.5 months."

P1 data • Cutaneous Melanoma • Uveal Melanoma

ACTallo: Developing an Allogeneic T Cell Therapy Platform Using Engineered γδ T Cells (ASGCT 2025) - "Autologous TCR-T therapies like ACTengine IMA203 targeting PRAME have demonstrated deep and durable objective responses in heavily pretreated patients with solid tumors in clinical trials...This data indicates that the ACTallo platform could be a promising pathway to enhance future TCR-T and CAR-T approaches for the benefit of cancer patients. Disease Focus of Abstract:Cancer Solid Tumors"

Graft versus Host Disease • Hematological Malignancies • Immunology • Oncology • Solid Tumor • Transplant Rejection • CD8 • PRAME

ACTallo: An engineered γδ T Cell therapy platform for adoptive cell therapies (CIMT 2025) - "Autologous CAR-T therapies have shown remarkable success against hematological malignancies while autologous TCR-T therapies such as ACTengine IMA203 targeting Preferentially Expressed Antigen in Melanoma (PRAME) have demonstrated positive responses in heavily pretreated patients with solid tumors in clinical trials...In vivo, a single dose of the engineered γδ T cells induced complete remission in a cell line derived xenograft tumor mouse model and the T cells persisted for several weeks. This data together with the versatility of the engineering strategy, demonstrates the potential of ACTallo as a promising platform for TCR-T cell therapies with the option for future exploration in CAR-T cell therapies."

IO biomarker • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Melanoma • Oncology • Solid Tumor • Transplant Rejection • PRAME

Beyond T cell persistence: comprehensive functionality assessment for ACTengine® IMA203 and IMA203CD8 TCR T-cell products (CIMT 2025) - P1 | "Along with long-term persistence of IMA203 T cells up to 2+ years, functionality assessment of a first set of ACTengine® IMA203 and IMA203CD8 samples demonstrated poly-functionality of the T cell products and maintained functionality up to 4.4 months post-infusion (latest timepoint analyzed). In summary, in-depth functionality assessment of ACTengine® IMA203 and IMA203CD8 T cell products and post-infusion PBMC samples provides valuable insights into the mode of action, determinants of durable therapy response as well as potential mechanisms of primary and secondary resistance."

IO biomarker • Melanoma • Oncology • Solid Tumor • CD8 • HLA-A • PRAME

Immatics Announces First Quarter 2025 Financial Results and Business Update (GlobeNewswire) - "IMA203 PRAME Cell Therapy: Randomized-controlled Phase 3 trial, SUPRAME, in previously treated advanced melanoma ongoing and expected to complete enrollment in 2026; IMA203 PRAME Cell Therapy: Phase 1b clinical trial ongoing with updated data in metastatic melanoma with substantially longer follow-up and additional uveal melanoma patients to be presented in an oral presentation at the 2025 ASCO Annual Meeting; IMA203CD8 PRAME Cell Therapy (GEN2): Phase 1a clinical trial in solid tumors ongoing with next data update, including dose escalation and ovarian cancer data, planned in 2025."

Enrollment status • P1 data • Cutaneous Melanoma • Ovarian Cancer

ACTengine® IMA203 Combined With mRNA-4203 (clinicaltrials.gov) - P1 | N=15 | Not yet recruiting | Sponsor: Immatics US, Inc.

New P1 trial • Cutaneous Melanoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Immatics Announces Upcoming Oral and Poster Presentation on IMA203 TCR T-cell Therapy at 2025 ASCO Annual Meeting (GlobeNewswire) - "Updated data from the Phase 1b trial of IMA203 in patients with metastatic melanoma with substantially longer follow-up compared to the last presentation in October 2024, and including data from additional uveal melanoma patients enrolled since then, will be highlighted in an oral presentation. In addition, a trial-in-progress poster on SUPRAME, the ongoing Phase 3 clinical trial evaluating IMA203 in patients with unresectable or metastatic cutaneous melanoma who have received prior treatment with a checkpoint inhibitor, will be presented at the conference."

P1 data • Trial status • Cutaneous Melanoma • Uveal Melanoma

Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial. (PubMed, Nat Med) - P1 | "Overall, IMA203 showed promising anti-tumor activity in multiple solid tumors, including refractory melanoma. ClinicalTrials.gov identifier: NCT03686124 ."

IO biomarker • Journal • P1 data • Hematological Malignancies • Melanoma • Oncology • Sarcoma • Solid Tumor • HLA-A • PRAME