IMA203 / Immatics - LARVOL DELTA

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

ACTengine IMA203 (PRAME) (GlobeNewswire) - "Patient enrollment for SUPRAME is forecasted 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 are enrolled in 1Q 2026. The final analysis is planned for 4Q 2026. Immatics aims to submit a Biologics License Application (BLA) in 1Q 2027 for full approval and to launch IMA203 in 3Q 2027....In addition to cutaneous melanoma, Immatics intends to expand the IMA203 TCR-T opportunity to treat uveal melanoma patients and will continue to evaluate IMA203 in this patient population through the ongoing Phase 1b trial."

FDA filing • Launch US • P3 data • Trial status • Cutaneous Melanoma • Melanoma • Uveal Melanoma

Development, Clinical Efficacy and Translational Analysis of PRAME Targeting with TCR Transduced T cells via IMA203 (SITC-SSC 2025) - No abstract available

Clinical • PRAME

SUPRAME-ACTengine® IMA203 vs. Investigator's Choice of Treatment in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma (clinicaltrials.gov) - P3 | N=360 | Recruiting | Sponsor: Immatics US, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Cutaneous Melanoma • Melanoma • Oncology • Skin Cancer • Solid Tumor

SUPRAME-ACTengine® IMA203 vs. Investigator's Choice of Treatment in Previously Treated, Unresectable or Metastatic Cutaneous Melanoma (clinicaltrials.gov) - P3 | N=360 | Not yet recruiting | Sponsor: Immatics US, Inc.

Metastases • New P3 trial • Cutaneous Melanoma • Melanoma • Oncology • Skin Cancer • Solid Tumor

Sequential Dosing of Next-Generation IMA203CD8 TCR-T-Cell Therapy Targeting PRAME in Combination with BRAF-/MEK-Inhibition in a Melanoma Patient with Progressive Disease - a Case Report (ASH 2024) - "Dexamethasone and Tocilizumab were initiated, which led to quick termination of ICANS but he had continuous high fever and intermittent oxygen dependency (CRS grade II), so that Anakinra was added alongside high-dose Dexamethasone and Tocilizumab on day +3. Additionally, as we could previously show with IMA203 TCR-T cells, IMA203CD8 TCR-T cells can be administered simultaneously with MAPKi and the combination is feasible, safe, and possibly beneficial. Although the individual contribution of the second IMA203CD8 infusion on the tumor response currently cannot be ultimately distinguished, longer follow-up and detailed assessment of the immune response will shed more light on the potential benefits of a delayed second infusion of T-cell therapies, as this novel approach could help increase anti-tumor activity of TCR- and CAR-T-cell therapies and enhance T-cell status potentially long-term with reduced T-cell exhaustion."

Case report • Clinical • Combination therapy • CNS Disorders • Melanoma • Oncology • Solid Tumor • IL2 • PRAME

A case series of IMA203 TCR-T-cell therapy targeting PRAME in combination with BRAF-/MEK-inhibition in two melanoma patients with active CNS metastases (SITC 2024) - "On day +2, the patient developed CRS and ICANS grade I, which were treated with tocilizumab/dexamethasone. Conclusions Here we show that application of IMA203 TCR-T in two heavily pretreated melanoma patients with active CNS metastases and the combination with MAPKi was safe with clinically manageable CRS and CNS side effects. Even though it is hard to discern the individual contribution of MAPKi and IMA203 to the observed CNS responses, we think that it is reasonable to assume CNS activity of IMA203 given disease progression under previous MAPKi treatment."

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

Enhanced pharmacology data of next-generation IMA203CD8 TCR-T monotherapy targeting PRAME (SITC 2024) - P1 | "Background ACTengine IMA203 TCR-T targeting an HLA-bound PRAME peptide demonstrated deep and durable responses in melanoma and beyond at doses up to 10bn TCR-T cells. Conclusions Next-generation TCR-T IMA203CD8 showed promising anti-tumor activity with manageable TEAEs at doses up to 0.800x109 TCR-T cells/m2 BSA. Updated translational and clinical data focused on melanoma and synovial sarcoma will be presented."

Monotherapy • Melanoma • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD4 • CD8 • HLA-A • PRAME

ACTengine IMA203 TCR-T targeting PRAME shows deep and durable anti-tumor activity in heavily pretreated solid cancer patients (SITC 2024) - P1 | "PFS and translational data will be presented at the conference. Conclusions IMA203 TCR-T was well tolerated and demonstrated deep and durable objective responses in heavily pretreated solid tumor patients, highlighting IMA203 as a novel and promising treatment option for melanoma and other solid cancers."

Clinical • Angiosarcoma • Breast Cancer • Lung Cancer • Melanoma • Mucosal Melanoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • HLA-A • PRAME

Combination of a TCR-engineered autologous PRAME-targeting T cell therapy with a PRAME-encoding mRNA for the treatment of solid tumors (SITC 2024) - "A FIH clinical combination study of IMA203 with the selected mRNA-LNP construct is planned. For the FIH phase 1 trial, the safety, tolerability and efficacy of the combination therapy will be evaluated in up to 15 patients with advanced or recurrent cutaneous melanoma and synovial sarcoma."

IO biomarker • Cutaneous Melanoma • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CD69 • CD8 • HLA-A • IFNG • IL2RA • PRAME • TNFRSF9

Preclinical Data on New Approaches for TCR-T Based Cell Therapies (GlobeNewswire) - "As part of Immatics’ long-term strategy to expand its PRAME franchise, the Company has conducted preclinical studies for the potential future clinical development of next-generation TCR-T-based cell therapies targeting PRAME to further enhance the efficacy and durability of IMA203. These efforts include the evaluation of TCR-T cells armored with membrane-bound IL-15 (mbIL15) targeting tumor types with low PRAME copy numbers, such as squamous non-small-cell lung cancer and squamous head and neck cancers....The preclinical data will be presented during poster sessions at SITC."

Preclinical • Lung Non-Small Cell Squamous Cancer • Squamous Cell Carcinoma of Head and Neck

ACTengine IMA203 Monotherapy Phase 1b Trial (GlobeNewswire) - P1b | N=476 | ACTengine (NCT03686124) | Sponsor: Immatics US | "The data announced today include all infused patients in the Phase 1b dose expansion part of the trial (N=412), consisting of the 28 melanoma patients...and 13 non-melanoma patients, of which 10 non-melanoma patients were reported on November 8, 2023....IMA203 monotherapy has maintained a favorable tolerability profile with no treatment-related Grade 5 events in the entire safety population (N=703 Phase 1a and Phase 1b patients across all dose levels and all tumor types)....The Company is on track to commence SUPRAME, the registration-enabling Phase 3 randomized-controlled clinical trial in melanoma for IMA203, in December 2024....Patient enrollment for SUPRAME is forecast to be completed in 2026, and a pre-specified interim analysis is planned for early 2026. Immatics aims to submit a Biologics License Application (BLA) in early 2027 for full approval."

FDA filing • New P3 trial • P1 data • Melanoma

The Society for Immunotherapy of Cancer Announces Late-Breaking Abstracts and Press Briefing Presented at 39th Annual Meeting (PRWeb) - "The Society for Immunotherapy of Cancer (SITC) received over 1,500 abstract submissions in 2024, and has announced titles and authors for 42 accepted Late-Breaking Abstracts (LBA). New for 2024, all of the Late-breaking Abstracts contain late-breaking data from interventional clinical trials in humans. The abstracts will be presented at SITC's upcoming 39th Annual Meeting & Pre-Conference Programs taking place November 6–10, 2024, in Houston, TX and virtually."

Clinical data • Melanoma • Non Small Cell Lung Cancer • Solid Tumor

Therapy of brain metastases with T cell receptor-modified T cells (ADO 2024) - "In addition to local ablative therapies (resections, stereotaxies) of the brain metastases, vemurafenib + cobimetinib was initiated in the case of BRAFV600E mutation, which resulted in stabilization for 1.5 years. Subsequent ICI therapy with ipilimumab + nivolumab did not provide any benefit to the superficial cerebral metastases...T cells are obtained using leukapheresis and then genetically modified so that they express a proprietary TCR (ACTengine® IMA203). After lymphodepletion (fludarabine 25 mg/m2, cyclophospamide 500 mg/m2), the patient's modified autologous T cells were reinfused... Different TCR therapies are currently being tested in clinical trials by various companies. TCR-T therapy also appears to be a promising treatment option for patients with brain metastases."

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

Therapeutic Challenges of Recurrent Mucosal Melanoma (ADO 2024) - "The patient then received nivolumab in combination with ipilimumab, accompanied by the intralesional administration of talimogene laherparepvec (T-VEC)...During maintenance therapy with nivolumab, local progression occurred again, so that therapy with paclitaxel 40 mg/m2 BSA was administered three times (Immunopax regimen). Due to further local progression, inclusion in the IMA-203 Phase I study (EudraCT No...The patient received bridging therapy with pembrolizumab until the start of the study. On the one hand, the case demonstrates the often poor response rate of existing therapies, but on the other hand it also demonstrates the variety of options for mucosal melanoma. It could serve as a stimulus for the development of optimized, individualized therapy concepts and clinical trials for mucosal melanoma."

Cutaneous Melanoma • Melanoma • Mucosal Melanoma • Oncology • Solid Tumor