Full Press Release Details
Immatics IMA203 PRAME Cell Therapy Data Presented
2025 ASCO Annual Meeting Continues to Show Strong
Anti-tumor Activity and Durability in Patients with Metastatic Melanoma
Texas and Tuebingen, Germany, May 31, 2025 - Immatics N.V. (NASDAQ: IMTX,
"Immatics" or the "Company"), a clinical-stage biopharmaceutical company active in the discovery and development
of T cell-redirecting cancer immunotherapies, today announced the presentation of expanded data from the ongoing Phase 1b clinical trial
evaluating IMA203 PRAME cell therapy in heavily pretreated patients with metastatic melanoma. The longer follow-up of patients demonstrates
a consistent and favorable tolerability profile as well as durable responses with a confirmed ORR of 56%. In addition, the Company provided
details from 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.
The data from the ongoing Phase 1b trial will be
presented on Saturday, May 31, 2025, during an oral presentation by Martin Wermke, M.D. The Trial in Progress poster (TiP) will be presented
at the conference on Monday, June 2, 2025, by Jason Luke, M.D., FACP, FASCO. The IMA203 slides, including the ASCO data and additional
data, are accessible in the Events & Presentations' section of the Investor & Media section of the Company's
"Patients with advanced melanoma post-failure
of checkpoint inhibition are left to face frequent and often rapid disease progression and limited long-term survival. These individuals
are in urgent need of new treatments that deliver deeper and more durable responses," said Cedrik Britten, M.D., Chief Medical Officer
at Immatics. "We believe the data presented today emphasize the strength, durability and tangible therapeutic potential of our one-time
infusion PRAME cell therapy, IMA203, in this patient population. These positive results reinforce our commitment to actively advance IMA203
through the ongoing Phase 3 SUPRAME trial to bring this PRAME therapy to the market as soon as possible."
"PRAME is a highly prevalent target that
is expressed in more than 50 cancers. This, combined with the data presented at ASCO, further strengthens our position as the global leader
in precision targeting of PRAME. We view our progress in melanoma as a critical step in our journey to building the broadest PRAME franchise
with the most indications and modalities and delivering novel PRAME immunotherapies to cancer patients with high unmet medical needs,"
said Harpreet Singh, Ph.D., Chief Executive Officer and Co-Founder at Immatics.
Oral Presentation Summary - IMA203 Phase 1b Trial
Patient Population: Heavily pretreated patients with metastatic
As of April 7, 2025, 33 heavily pretreated patients
with metastatic melanoma were administered a one-time infusion of IMA203 at the recommended Phase 2 dose (RP2D, 1 to 10 billion total
TCR T cells) in the Phase 1b dose expansion. The treated patient population consisted of cutaneous melanoma (n=14), uveal melanoma (n=16),
mucosal melanoma (n=2) and melanoma of unknown primary (n=1). Patients had a median of 2 lines of prior systemic treatments. The subgroup
of patients with cutaneous melanoma had a median of 2.5 lines of prior systemic treatments, thereof a median of 2 lines of prior immune
checkpoint inhibitors.
Safety: Favorable tolerability
The safety population included 74 patients combined
from the Phase 1a dose escalation and Phase 1b dose expansion across all dose levels and all tumor types. IMA203 has maintained a favorable
tolerability profile.
The most frequent treatment-emergent adverse events
were anticipated cytopenias associated with lymphodepletion. Expected and manageable cytokine release syndrome (CRS) was mostly Grades
1 and 2, which is consistent with the mechanism of action (Grade 1: 37%, Grade 2: 47%, Grade 3: 11%, Grade 4: 0%). No patients experienced
long-term CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred infrequently, was manageable and mostly mild (Grade
1: 5%, Grade 2: 4%, Grade 3: 4%, Grade 4: 0%). No IMA203-related Grade 5 events were observed.
Tolerability in the Phase 1b melanoma subset was
generally consistent with the full IMA203 tolerability profile.
Anti-tumor activity and durability: Encouraging
anti-tumor activity of IMA203 PRAME cell therapy, including durable responses up to >2.5 years with longer follow-up
| All melano ma 1 , 2 (n=33) | Cutaneous melanoma (n=14) | Uveal melanoma 2 (n=16) | |
| cORR | 56% (18/32) | 50% (7/14) | 67% (10/15) |
| ORR | 64% (21/33) | 57% (8/14) | 69% (11/16) |
| DCR | 91% (30/33) | 93% (13/14) | 88% (14/16) |
| mDOR (range) / mFU [mo] | 12.1 (1.8+, 32.6+) / 13.4 | NR 3 (4.2, 32.6+) / 16.7 | 11.0 (1.8+, 31.6) / 13.4 |
| mPFS (range) / mFU [mo] | 6.1 (1.4, 34.0+) / 14.4 | 6.0 (1.4, 34.0+) / 14.4 | 8.5 (1.4, 32.9) / 8.7 |
| mOS (range) / mFU [mo] | 15.9 (2.4, 34.2+) / 14.4 | 13.9 (2.4, 34.0+) / 14.4 | 16.2 (3.2+, 34.2+) / 14.5 |
The PFS rate was 53% at six months and 27% at 12
months. The overall survival rate was 61% at 12 months. In addition, 42% (14/33) of patients had a deep response ( 50% tumor reduction)
with a mPFS of 12.9 months.
1 Melanoma efficacy population includes
n=3 patients with other melanoma subtypes (n=2 mucosal melanoma, n=1 melanoma of unknown primary; data can be found in the IMA203 slides).
2 cORR excludes 1 uveal melanoma
patient with ongoing unconfirmed PR.
PD: progressive disease; BL: baseline; PR: partial response; (c)ORR: (confirmed) objective response rate; DCR: disease control rate at week 6; mDOR: median duration of response; mFU: median follow-up; mPFS: median progression-free survival; mOS: median overall survival
Translational analyses demonstrated that treatment
with IMA203 resulted in the shrinkage of metastatic target lesions throughout the body. This included reductions in difficult-to-treat
metastases, such as liver, lung, lymph node, abdomen/peritoneum, skin and others. Some individual lesions had a complete resolution (-100%).
All patients (n=3) who had a best overall response of progressive disease according to RECIST 1.1 experienced shrinkage of individual
The positive Phase 1b data and high PRAME prevalence
(~90-95% in melanoma) reinforce the potential of IMA203, which is currently being evaluated in the ongoing SUPRAME Phase 3 trial in previously
treated advanced or metastatic cutaneous melanoma, as well as the continued Phase 1b expansion into uveal melanoma.
Trial-in-Progress Poster Summary -
IMA203 SUPRAME Phase 3 Trial
Based on the positive clinical data and supported
by the FDA RMAT designation4, Immatics advanced its PRAME cell therapy, IMA203, into the randomized-controlled Phase 3
SUPRAME trial (NCT06743126).
SUPRAME is a prospective, multicenter, open-label,
randomized, actively controlled Phase 3 clinical trial evaluating the efficacy, safety and tolerability of IMA203 vs. investigator's choice
in ~360 patients with unresectable or metastatic cutaneous melanoma who have received prior treatment with a checkpoint inhibitor. Patient
eligibility is determined by protocol inclusion/exclusion criteria, including HLA screening. If patients are HLA-A*02:01 positive and
meet the eligibility criteria, they will undergo leukapheresis and be randomized 1:1. Patients in the IMA203 arm will undergo lymphodepletion
with cyclophosphamide (500 mg/m2 x 4 days) and fludarabine (30 mg/m2 x 4 days), subsequent infusion of 1-10 x109
IMA203 PRAME-directed TCR T cells, followed by low-dose IL-25 (subcutaneous). Patients in the control arm will receive either
nivolumab/relatlimab, nivolumab, ipilimumab, pembrolizumab, lifileucel (in the US), or chemotherapy based on investigator's choice.
The primary endpoint is blinded independent central review ("BICR")-assessed (RECIST 1.1) PFS. Secondary endpoints include
OS, ORR, safety and patient-reported outcomes about quality of life.
4Includes all benefits of Breakthrough Therapy Designation.
51m IU daily days 1-5 and twice daily
days 6-10, total dose is approx. only 5% of the overall dose for high-dose IL-2 given typically with TIL therapy (Sarnaik et al. 2021
Journal of Clinical Oncology).
The expected median PFS in this post-checkpoint
inhibitor patient population6 is 2-3 months, and the IMA203 Phase 1b data presented today at ASCO indicate a continued median
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)7, 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.
PRAME is a target expressed in more than 50 cancers.
Immatics is the global leader in precision targeting of PRAME and has the broadest PRAME franchise with the most PRAME indications
and modalities. The Immatics PRAME franchise currently includes three product candidates, two therapeutic modalities and a combination
therapy that target PRAME: IMA203 PRAME cell therapy, IMA203CD8 PRAME cell therapy (GEN2), IMA402 PRAME bispecific, IMA203 in combination
with Moderna's PRAME adaptive immune modulating therapy.
About IMA203 PRAME Cell Therapy
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
response. IMA203 PRAME cell therapy is currently being evaluated in a registration-enabling randomized controlled Phase 3 trial, "SUPRAME,"
in patients with unresectable or metastatic cutaneous melanoma who have disease progression on or after treatment with at least one checkpoint
inhibitor. In parallel, the Phase 1b clinical trial in patients with PRAME cancers is ongoing with a focus on uveal melanoma.