Investigational Drug
IMA203
HealthScout AI Analysis
Show HealthScout AI Analysis
Overview
IMA203 is an autologous TCR-T cell therapy engineered to recognize a PRAME-derived peptide presented by HLA-A*02:01 on tumor cells. Early-phase clinical data in multiple advanced solid tumors, including melanoma and sarcoma, show antitumor activity and a manageable safety profile. A randomized Phase 3 trial (SUPRAME; NCT06743126) in previously treated cutaneous melanoma began enrolling in early 2025. (doi.org)
Mechanism of action
- Target: PRAME (preferentially expressed antigen in melanoma), a cancer/testis antigen broadly expressed across solid tumors with limited expression in normal tissues. The IMA203 TCR recognizes the HLA‑A*02:01–restricted PRAME peptide “SLLQHLIGL.” (doi.org)
- Modality: Patient T cells are genetically modified ex vivo to express an affinity‑enhanced, PRAME‑specific TCR; patients receive lymphodepleting chemotherapy followed by a single IMA203 infusion and low‑dose subcutaneous IL‑2. (doi.org)
Efficacy
Phase 1 (NCT03686124; multi‑tumor, HLA‑A*02:01+ PRAME+ patients)
- Among 40 infused patients, overall response rate (unconfirmed or confirmed) was 52.5% (21/40); confirmed ORR was 28.9% (11/38). Median duration of response was 4.4 months (range 2.4–23.0). Responses were observed across multiple indications, with higher confirmed response frequencies at higher IMA203 doses. (doi.org)
Melanoma subset (Phase 1b update presented at ASCO 2025)
- Reported 6‑ and 12‑month PFS rates of 53% and 27%, respectively; 12‑month OS rate of 61%; and deep responses (≥50% tumor reduction) in 42% (14/33) of patients assessed. These data supported advancement to Phase 3. Note: company-reported conference data. (immatics.gcs-web.com)
Ongoing randomized trial
- SUPRAME (NCT06743126) compares IMA203 to investigator’s choice (e.g., nivolumab/relatlimab, lifileucel, single‑agent PD‑1, ipilimumab, or chemotherapy) with BICR‑assessed PFS as the primary endpoint. Enrollment target ≈360 patients. (cdek.pharmacy.purdue.edu)
Safety
- In Phase 1 (40 infused; 41 started lymphodepletion), IMA203 was generally manageable: severe cytokine release syndrome occurred in 4.9% (2/41), and severe neurotoxicity was not observed. Cytopenias were common, consistent with lymphodepletion. The maximum tolerated dose was not reached. (doi.org)
Development status and designations
- FDA granted RMAT designation to IMA203 in October 2023 for multiple PRAME‑expressing solid tumors, facilitating expedited interactions and potential priority review pathways. (investors.immatics.com)
- A global Phase 3 program in cutaneous melanoma is underway with interim analysis planned after a prespecified number of PFS events; BLA submission is targeted for 2027 per company guidance. (rss.globenewswire.com)
Further reading
- Wermke M, Araujo DM, et al. Autologous T cell therapy for PRAME+ advanced solid tumors in HLA‑A*02+ patients: a phase 1 trial. Nature Medicine (2025). (doi.org)
- Phase 1 trial listing (NCT03686124): design, procedures, and IL‑2 support. (mycancergenome.org)
- Phase 3 SUPRAME trial listing (NCT06743126): randomized design and comparators. (cdek.pharmacy.purdue.edu)
- ASCO 2025 company summary of melanoma Phase 1b outcomes (conference presentation). (immatics.gcs-web.com)
- FDA RMAT designation announcement for IMA203. (investors.immatics.com)
Notes: IMA203 is also referenced in some registries as anzutresgene autoleucel (anzu‑cel). (cdek.pharmacy.purdue.edu)
Last updated: Oct 2025
Active trials using IMA203
Found 3 active trials using this drug:
HealthScout AI summary: Adults with HLA‑A*02:01–positive unresectable or metastatic cutaneous melanoma (post–PD‑1) or synovial sarcoma needing further therapy receive autologous PRAME‑targeted TCR‑T cells (ACTengine IMA203) after lymphodepletion plus low‑dose IL‑2, combined with a PRAME mRNA vaccine (mRNA‑4203) to boost PRAME‑specific T‑cell responses. Key exclusions include active brain metastases, significant autoimmune/cardiac disease, prior allogeneic transplant, active viral infections, and hypersensitivity to study agents.
ClinicalTrials.gov ID: NCT06946225
HealthScout AI summary: Adults with unresectable or metastatic cutaneous (including acral) melanoma who are HLA‑A*02:01 positive and have progressed after PD‑1 therapy (and BRAF‑directed therapy if mutated) are randomized to autologous PRAME‑targeted TCR‑T cells (IMA203) after lymphodepletion with short-course low‑dose IL‑2 support versus investigator’s choice of approved therapies (e.g., nivolumab/relatlimab, anti‑PD‑1, ipilimumab, lifileucel, or chemotherapy). Key exclusions include mucosal/uveal melanoma, active CNS disease, significant autoimmune/cardiac comorbidities, active infections, and LDH >2× ULN.
ClinicalTrials.gov ID: NCT06743126
HealthScout AI summary: Adults with PRAME-expressing, recurrent/refractory solid tumors (HLA‑A*02:01+, ECOG 0–1) receive autologous PRAME‑specific TCR‑T therapy (IMA203 or IMA203CD8) after cyclophosphamide/fludarabine lymphodepletion, with low‑dose IL‑2 support and an arm combining IMA203 with nivolumab. IMA203 targets a PRAME peptide via engineered TCR, while IMA203CD8 co‑expresses CD8αβ to enable CD4/CD8 T‑cell tumor killing; nivolumab (PD‑1 inhibitor) is tested for potential synergy.
ClinicalTrials.gov ID: NCT03686124
