IMA203CD8 / Immatics - LARVOL DELTA

A phase I trial of IMA203CD8, a PRAME-directed TCR T cell therapy in PRAME-positive solid tumors (ESMO-IO 2025) - P1/2 | "Complete data, including recently treated pts will be presented.Conclusions IMA203CD8 demonstrated manageable safety and encouraging activity in pts with PRAME+ solid tumors with limited treatment options, including ovarian cancer. Dose escalation with and without IL-2 is ongoing.Clinical trial identification NCT03686124.Editorial acknowledgement Clinical Care Solutions provided support in the writing of this abstract.Legal entity responsible for the study Immatics."

P1 data • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • CD4 • CD8 • HLA-A • PRAME

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 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

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

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 IMA203CD8 TCR-T (GEN2) Monotherapy (PRAME) (GlobeNewswire) - "The next clinical data update including dose escalation and ovarian cancer is planned in 2025."

P1 data • Ovarian Cancer

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 IMA203CD8 (GEN2) Monotherapy Phase 1 Dose Escalation Trial (GlobeNewswire) - P1b | N=476 | ACTengine (NCT03686124) | Sponsor: Immatics US | "As of data cut-off on September 30, 2024, 444 heavily pretreated HLA-A*02:01 and PRAME-positive patients with solid tumors were infused with IMA203CD8 monotherapy....10 of 17 responses were ongoing, of which three confirmed responses were ongoing at 14+, 15+ and 24+ months....Deep responses with ≥50% tumor size reduction were observed in 11 out of 17 responders. This group included two patients with complete response of target lesions, of which one patient showed a complete metabolic response according to PET-CT scan. 41% (14/34) confirmed objective response rate (cORR) and 41% (17/41) objective response rate (ORR). Median duration of response (mDOR) of 9.2 months at a median follow-up (mFU) of 13.1 months. Tumor shrinkage7 of 84% (32/38) and disease control rate8 at week 6 of 85% (34/40)."

P1 data • Solid Tumor

Immatics Announces Upcoming Oral and Poster Presentations at the Society for Immunotherapy of Cancer Annual Meeting 2024 (GlobeNewswire) - "Immatics N.V...today announced upcoming oral and poster presentations at the 39^th Annual Meeting of the Society for Immunotherapy of Cancer in Houston, Texas from November 6 - 10, 2024."

Clinical data • Solid Tumor

ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors (clinicaltrials.gov) - P1 | N=476 | Recruiting | Sponsor: Immatics US, Inc. | N=186 ➔ 476

Enrollment change • Breast Cancer • Oncology • Sarcoma • Solid Tumor • Triple Negative Breast Cancer

Immatics Announces Second Quarter 2024 Financial Results and Business Update (GlobeNewswire) - "The next data update, which will include translational and clinical data for IMA203, as well as further details on the clinical trial design for the planned IMA203 Phase 2/3 study, will be presented in 2H 2024 at a medical conference....Immatics is continuing dose escalation of IMA203CD8 (GEN2) with the goal of defining the optimal dose for further development. The next data update for IMA203CD8 (GEN2) is planned for 2H 2024 with a focus on continued dose escalation data in melanoma patients."

Clinical protocol • P1 data • Melanoma

Immatics Announces Full Year 2023 Financial Results and Corporate Update (GlobeNewswire) - "ACTengine IMA203 (PRAME): The full trial design is currently being developed and is subject to further alignment with the FDA as part of the ongoing discussions. The Phase 2/3 trial is planned to start in 2024; A next data update for both Phase 1b cohorts with IMA203 GEN1 and IMA203CD8 GEN2 is planned for 2H 2024."

Clinical protocol • New P2/3 trial • P1 data • Oncology • Solid Tumor

Immatics Reports Interim Clinical Data from ACTengine IMA203 and IMA203CD8 TCR-T Monotherapies Targeting PRAME in an Ongoing Phase 1 Trial (GlobeNewswire) - P1 | N=186 | NCT03686124 | Sponsor: Immatics US, Inc. | "IMA203CD8 GEN2 TCR cell therapy targeting PRAME – first clinical data from Cohort C: Manageable tolerability, dose escalation ongoing; Initial clinical activity with 56% (5/9) cORR and 58% ORR (7/12) observed during dose escalation dose levels 3 and 4; 6 out of 7 responses ongoing with longest response at >12 months; Reduction of tumor size was observed in 11 out of 12 patients, with a deepening of response from initially stable disease (SD) to partial response (PR) observed in two patients."

P1 data • Oncology • Solid Tumor

ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors (clinicaltrials.gov) - P1 | N=186 | Recruiting | Sponsor: Immatics US, Inc. | N=102 ➔ 186

Combination therapy • Enrollment change • Monotherapy • Oncology • Solid Tumor

Immatics Announces Full Year 2022 Financial Results and Corporate Update (GlobeNewswire) - "ACTengine^® IMA203 (PRAME)...Immatics’ focus for 2023 is to advance its monotherapy product candidates, 1st-generation IMA203 TCR-T (Cohort A) and 2nd-generation IMA203CD8 TCR-T (Cohort C) in the last-line therapy setting. Data generated throughout 2023 with longer follow-up to assess durability of response is intended to identify the most promising cohort to advance towards pivotal trials and potential commercialization. The clinical data update on all three cohorts is planned for 2H 2023."

P1 data • Oncology • Solid Tumor

Immatics Reports Interim Clinical Data Update on ACTengine IMA203 TCR-T Monotherapy Targeting PRAME (GlobeNewswire) - P1 | N=102 | ACTengine (NCT03686124) | Sponsor: Immatics US, Inc. | "Confirmed objective response rate (cORR): 50% (6/12) at target dose or above with at least 1 billion infused TCR-T cells across Phase 1a and 1b; thereof 80% cORR (4/5) in Phase 1b patients alone with all responses ongoing at data cut-off; Confirmed responses across different solid tumor types: cutaneous melanoma, ovarian cancer, head and neck cancer, uveal melanoma, and synovial sarcoma....IMA203 TCR-T is part of Immatics’ strategy to leverage the full clinical potential of targeting PRAME; next data read-outs on IMA203 monotherapy, IMA203 in combination with a checkpoint inhibitor and 2nd generation IMA203CD8 planned during 2023....In addition, we are excited to start a first-in-human trial with our half-life extended Bispecific against PRAME, TCER^® IMA402, also in 2023."

New trial • P1 data • Cutaneous Melanoma • Gynecologic Cancers • Head and Neck Cancer • Melanoma • Ocular Melanoma • Oncology • Ovarian Cancer • Sarcoma • Skin Cancer • Solid Tumor • Synovial Sarcoma • Uveal Melanoma

Immatics Announces First Cancer Patient Treated with Second-Generation ACTengine TCR-T Candidate IMA203CD8 Targeting PRAME (GlobeNewswire) - "Immatics N.V...announced the treatment of the first patient in its Phase 1b expansion cohort C (NCT03686124) evaluating IMA203CD8, the company’s 2nd generation TCR-T monotherapy approach where a proprietary CD8αβ co-receptor is added to PRAME-specific IMA203 T cells....The IMA203CD8 Phase 1b dose expansion cohort is expected to enroll up to 24 patients with different types of solid tumors across several clinical trial sites in the U.S. and in Germany....Each Phase 1b expansion cohort is designed to evaluate the observed objective response rate, demonstrate durability of response and provide the basis for entering registration trials. The next data readout for the IMA203 monotherapy cohort at RP2D is expected during 2H 2022 and an initial data readout for Cohort B and Cohort C is planned for YE2022."

P1 data • Trial status • Oncology • Solid Tumor

ACTengine® IMA203/IMA203CD8 as Monotherapy or in Combination With Nivolumab in Recurrent and/or Refractory Solid Tumors (clinicaltrials.gov) - P1 | N=102 | Recruiting | Sponsor: Immatics US, Inc. | N=42 ➔ 102

Combination therapy • Enrollment change • Monotherapy • Oncology • Solid Tumor

Clinical outcomes of solid cancer patients treated with autologous TCR-T cells targeting PRAME in the ongoing ACTengine® IMA203 phase 1 dose escalation trial (CIMT 2022) - "IMA203 T cells are infused after lymphodepletion with fludarabine, and cyclophosphamide followed by low-dose IL-2. In summary, IMA203 shows a manageable safety profile and, to our knowledge, is the first TCR-T product candidate associated with frequent objective responses across multiple solid tumors at doses below 1 billion transduced T cells. Three expansion cohorts are currently being initiated to further study the safety and anti-tumor activity of IMA203 in solid tumors: IMA203 monotherapy at target dose, combination with a checkpoint inhibitor and a next-gen product candidate IMA203CD8 utilizing IMA203 co-transduced with a CD8 co-receptor."

Clinical • Clinical data • P1 data • Eye Cancer • Head and Neck Cancer • Hematological Disorders • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • Uveal Melanoma • CD8 • HLA-A • PRAME

Enhanced preclinical anti-tumor activity of PRAME-specific next-generation TCR-T cells through CD8αβ co-expression (CIMT 2022) - "Here, we show preclinical data from our next-generation product candidate IMA203CD8 utilizing the IMA203 TCR co-transduced with a CD8 co-receptor. The differential functional profiles of TCR-T cells co-expressing different types of CD8 constructs suggests that optimizing the type of co-receptor is relevant to maximize anti-tumor response and reveals CD8αβ to be the optimal co-receptor for the IMA203 PRAME TCR. Harnessing the anti-tumor potency of CD4 T cells may enhance depth and durability of anti-tumor responses and potentially improve the clinical outcome of TCR-T in patients with solid cancer."

Preclinical • Oncology • Solid Tumor • CD4 • CD8 • HLA-A • PRAME

Immatics Announces Third Quarter 2021 Financial Results and Provides Business Update (GlobeNewswire) - "IND submission for IMA203CD8 as part of the Phase 1b study expansion cohort is expected in the first half of 2022...TCER® IMA402...Production of GMP material for a Phase 1 clinical study is planned in 2022...R&D expenses were €21.2 million ($24.5 million1) for the three months ended September 30, 2021...The increase is mainly due to expanded clinical activities for the ACTengine® IMA200 series, as well as GMP manufacturing for the TCER® compound, IMA401."

Commercial • New P1 trial • Hematological Malignancies • Oncology • Solid Tumor

Immatics Reports Clinical Responses across Multiple Solid Tumor Types in Ongoing ACTengine IMA203 Phase 1a Trial Targeting PRAME (GlobeNewswire) - "The IMA203CD8 product candidate has the potential to harness the potency of CD4 T cells. Engagement of CD4 T cells, in addition to CD8 T cells, might further enhance depth and durability of anti-tumor response and clinical outcome of TCR-T in solid cancer patients...IND submission for IMA203CD8 cohort is expected in the first half of 2022."

IND • Preclinical