Phase 1 Clinical Update of IMA203, an Autologous TCR T Targeting PRAME in Patients with PD1 Refractory Metastatic Melanoma
Martin Wermke1, Winfried Alsdorf2, Dejka M. Araujo3, Antonia Busse4, Manik Chatterjee5, Leonel Hernandez Aya6, Norbert Hilf7, Tobias A.W. Holderried8, Amir A. Jazaeri3, M. Alper Kursunel7, Andrea Mayer-Mokler7,
Regina Mendrzyk7, Ali Mohamed9, Sapna P. Patel10, Ran Reshef11, Apostolia-Maria Tsimberidou3, Steffen Walter9, Toni Weinschenk7, Jason J. Luke12, Cedrik M. Britten7
1University Hospital Dresden, Germany; 2University Medical Center Hamburg-Eppendorf, Germany; 3The University of Texas, MD Anderson Cancer Center, Houston, Texas, USA; 4Charité-Universitätsmedizin Berlin, Germany; 5University Hospital Wuerzburg, Germany; 6University of Miami, Florida, USA; 7Immatics GmbH, Tuebingen, Germany; 8University Hospital Bonn, Germany; 9Immatics US Inc, Stafford, Texas, USA; 10University of Colorado Cancer Center, Aurora, Colorado, USA; 11Columbia University,
New York, New York, USA; 12University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting
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Chicago, IL • May 30 - June 3, 2025
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Frequent recurrence and limited long-term survival with unresectable or metastatic melanoma highlight the critical need for new treatments that deliver deeper, more durable responses1-3
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IMA203 is a PRAME-directed TCR T-cell therapy engineered to recognize an intracellular PRAME-derived peptide presented by HLA-A*02:01 on the cell surface and initiate a potent and specific anti-tumor response4
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IMA203 exhibited favorable tolerability, with anticipated lymphodepletion-associated cytopenias, mostly mild-to-moderate CRS,
infrequent ICANS, and no IMA203-related grade 5 events
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One-time infusion of IMA203 has promising clinical activity in heavily pretreated patients with metastatic melanoma (n=33):
- cORR: 56% (18/32)
- mDOR: 12.1 mo (range: 1.8+, 32.6+) at mFU of 13.4 mo
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mPFS: 6.1 mo (range: 1.4, 34.0+) at mFU of 14.4 mo
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mOS: 15.9 mo (range: 2.4, 34.2+) at mFU of 14.4 mo
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Encouraging activity was seen in both cutaneous melanoma (cORR 50%) and uveal melanoma (cORR 67%)
Data cutoff: April 7, 2025.
HLA, human leukocyte antigen; PRAME, preferentially expressed antigen in melanoma; TCR, T-cell receptor.
1. Mooradian MJ, et al. Oncology (Williston Park). 2019;33:141-148. 2. Hamid O, et al. Ann Oncol. 2019;30:582-588. 3. Goldinger SM, et al. Eur J Cancer. 2022;162:22-33. 4. Wermke M, et al. Nat Med. 2025; doi: 10.1038/s41591-025- 2
03650-6 [online ahead of print].
PRAME is expressed in more
than 50 cancers
Precision targeting of PRAME peptide with IMA2031
|
PRAME prevalence in selected indications |
|
|
Indication |
% PRAME positive tumorsa |
|
Cutaneous Melanoma |
95% |
|
Uterine Carcinoma |
95% |
|
Uterine Carcinosarcoma |
95% |
|
Synovial Sarcoma |
95% |
|
Uveal Melanoma |
90% |
|
Mucosal melanoma |
90% |
|
Ovarian Carcinoma |
85% |
|
Squamous Cell NSCLC |
70% |
|
TNBC |
65% |
a Data on file: PRAME target prevalence is based on a proprietary mass spec-guided expression threshold applied to RNAseq data (approximate values; values between 95-100% shown as 95%).
HLA, human leukocyte antigen; NSCLC, non-small cell lung cancer; PRAME, preferentially expressed antigen in melanoma; TCR, T-cell receptor; TNBC, triple-negative breast cancer. 3
1 Wermke M, et al. Nat Med. 2025; doi: 10.1038/s41591-025-03650-6 [online ahead of print].
Key Objectives
Primary:
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Tolerability
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Determination of RP2D (Phase 1a)
Secondary:
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IMA203 T cell engraftment, persistence
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Efficacy
Key Eligibility Criteria
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Confirmed advanced and/or metastatic solid tumor
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Patients ≥ 18 years of age
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ECOG performance status 0-1
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HLA-A*02:01 and PRAME positive
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Patients having received, or not been eligible for all available indicated SOC treatment
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Adequate organ function
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No active brain metastasis
Data cutoff: April 7, 2025.
a Outpatient administration at investigator's discretion.
SCREENING/MANUFACTURING
TREATMENT / OBSERVATION FU
HLA-A*02:01 Testing
(blood) Inclusion of HLA-A*02:01-
positive patients
Leukapheresis
IMA203
One-time infusion
Prevalence1:
US: 41%
EU: 48%
Manufacturing
of IMA203
~2 weeks turnaround time (applying CD8/CD4 T cell selection, incl. QC release testing)
95% success rate to reach RP2D
PRAME Testing
Biopsy or archived tissue Inclusion of PRAME-positive patients
Lymphodepletion
Fludarabine 30mg/m2Cyclophosphamide 500mg/m2Days -6 to -3
Low Dose IL-2a
1M IU SC Days 1-5;
1M IU SC BID Days 6-10
Patient Journey
Total Safety
Population
(N=74)
RP2D defined at
1-10x109TCR T cells
n=1 in Phase 1a
started lymphodepletion but did not receive IMA203
n=27
Phase 1a Dose Escalation
(DL1-4)
n=46
Phase 1b Dose Expansion
(RP2D)
n=13
non-melanoma
Melanoma Efficacy Populationa
(n=33)
n=14
cutaneous melanoma
n=16
uveal melanoma
n=3
other melanomab
Data cutoff: April 7, 2025.
a Melanoma efficacy population excludes 1 patient with uveal melanoma with ongoing unconfirmed PR from cORR; bMucosal melanoma n=2, melanoma of unknown primary n=1;
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Immatics NV published this content on May 31, 2025, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 31, 2025 at 12:04 UTC.
