Phase 1a study results for IMA203CD8, a PRAME-directed T-cell receptor (TCR) T-cell therapy, in ovarian cancer.

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5509 Background: Pts with advanced ovarian cancer (OC) that progresses after platinum-based chemotherapy and subsequent treatment are lacking therapeutic options for durable clinical benefit. TCR T-cell therapies enable immune recognition of intracellular tumor antigens presented by HLA, expanding the therapeutic landscape beyond targets accessible to conventional immunotherapies. PRAME is a cancer-associated antigen expressed across >50 cancers, including OC. IMA203CD8 is a TCR T-cell therapy that engineers CD8+ and CD4+ T cells to detect and destroy PRAME-expressing tumor cells that evade conventional therapeutic approaches. Results from a phase 1a basket trial (NCT03686124) indicated the potential to target several PRAME+ tumors. Here we present updated dose-escalation results for the subset of pts with OC. Methods: Pts were ≥18 y, HLA-A*02:01+, had R/R solid tumors, measurable disease (RECIST 1.1), ECOG PS 0-1, and had exhausted SOC options, including platinum therapy. Following leukapheresis and IMA203CD8 manufacture, pts underwent lymphodepletion (LD) with Cy (500 mg/m 2 × 4 d) and Flu (30 mg/m 2 × 4 d), followed by IMA203CD8 infusion +/- low-dose SUBQ IL-2. Dose escalation is ongoing. Results: As of Oct 27, 2025, 16 heavily pretreated pts with OC were infused with IMA203CD8. Most common TEAEs were LD-related cytopenias (100%). Cytokine release syndrome occurred in 100% of pts and was mostly mild to moderate (G1: 44%, G2: 50%, G3: 6%). Immune effector cell–associated neurotoxicity syndrome occurred in 1 pt (G1: 6%). Tolerability in pts with OC was generally consistent with the known IMA203CD8 safety profile. Eleven pts were efficacy evaluable with ≥1 post-baseline scan (median 4 prior lines of therapy) after treatment with IMA203CD8 across escalating dose levels (median: 2.26×10 9 total TCR T cells; range: 1.4-7.1×10 9 TCR T cells). Tumor reduction was observed in 7 pts with maximum reduction of 74%; 3 responses were >6 mo and durable disease control occurred for up to 12 mo. A dose-dependent signal of activity was observed in pts treated at higher doses (n=5; range: 2.3-7.1×10⁹ TCR T cells), including 2 confirmed partial responses (PRs) with 1 ongoing metabolic complete response (CRs) at 6 mo, and 1 unconfirmed PR. All responses were observed in pts without post-infusion low-dose IL-2. Updated results from ≥20 efficacy-evaluable pts (including several unconfirmed PRs and CRs after data cutoff) with longer follow-up will be presented. Conclusions: In pts with metastatic and/or relapsed OC, IMA203CD8 demonstrated a tolerability profile consistent with prior experience in other solid tumors and encouraging dose-dependent antitumor activity, including durable objective responses according to RECIST. Dose escalation with and without IL-2 at higher doses is currently ongoing to determine RP2D and unlock the full potential of IMA203CD8 in OC. Clinical trial information: NCT03686124 .

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