The future of solid tumor immunotherapy is here — and it’s cellular. As I prepare for the next chapter in my career (officially signed, contract in hand — more soon!), I’ve never been more energized by the momentum we’re seeing in TIL, TCR, and engineered cell therapies. One standout at ASCO 2025 was the evolving data around Inmate’s PRAME-targeted TCR therapy presented by Dr Martin Wermke.
One of the most exciting developments in solid tumor cell therapy right now is the emergence of TCR-based treatments like IMA203, a PRAME-targeted TCR-T cell therapy developed by Inmatics. At ASCO 2025, Dr. Martin Wermke presented updated phase 1 results that continue to turn heads in the immunotherapy space—especially for those of us closely watching the evolution of cellular therapies beyond hematologic malignancies.
We’ve long seen breakthroughs in solid tumor immunotherapy through TIL therapy, particularly in melanoma. TCR therapy has also gained traction, with Afamicel becoming the first approved TCR FDA approved product in synovial sarcomas. But IMA203, developed by Immatics, represents a different and promising direction—targeting the PRAME antigen in solid tumors using an engineered TCR T-cell platform.
Why PRAME?
PRAME (Preferentially Expressed Antigen in Melanoma) is a cancer/testis antigen expressed in a wide range of solid tumors. Its expression is notably high—over 90%—in tumors like cutaneous melanoma, uveal melanoma, synovial sarcomas, and uterine carcinomas. It’s also expressed in about 65% of triple-negative breast cancers and 70% of squamous non-small cell lung cancers.
Its prevalence and tumor-specific expression make PRAME an attractive target for TCR therapy, which relies on recognizing intracellular tumor antigens presented by MHC complexes. In this case, IMA203 targets PRAME presented on HLA-A*02:01, which remains the eligibility-defining factor for this approach. Meaning as a patient, they would be tested first to see if they have HLA-A*02:01 which is common in half the population.
The IMA203 Phase 1 Trial: Design and Key Findings
This first-in-human phase 1 trial enrolled 74 patients with advanced PRAME-positive solid tumors, all of whom had progressed on standard therapies. After confirming HLA-A*02:01 status by blood and PRAME expression via tumor biopsy, patients underwent leukapheresis and received a one-time infusion of IMA203 following lymphodepleting chemotherapy.
Treatment Overview:
- Lymphodepletion: Fludarabine (30 mg/m²) and Cyclophosphamide (500 mg/m²) on Days -6 to -3
- IMA203 infusion: One-time, individualized TCR-T cell infusion
- IL-2 support: Low-dose subcutaneous IL-2 (1 million IU daily on Days 1–5, BID on Days 6–10)
Patient Breakdown:
- 14 patients with cutaneous melanoma
- 16 with uveal melanoma
- Total of 33 melanoma patients
Key Results in Melanoma:
- Overall Response Rate (ORR): 56% across all melanoma patients
- ORR in cutaneous melanoma: 57%
- ORR in uveal melanoma: 67%
- Disease Control Rate (DCR): 91%
- Median Progression-Free Survival (PFS): ~6 months
- Median Overall Survival (OS): ~15 months
- Duration of Response: Ongoing for many, with some beyond 30 months
- Responses observed across various metastatic sites (liver, lung, lymph nodes)
Toxicities were largely manageable. Cytokine release syndrome (CRS) occurred in about 10% of patients at Grade 3, with no Grade 4 or 5 events reported. Most side effects—largely from lymphodepletion—were transient and resolved within the first two weeks.
SUPRAME: The Phase 3 Trial Now Underway
These compelling early results have paved the way for the SUPRAME trial—a randomized Phase 3 study comparing IMA203 to investigator’s choice of therapy in patients with unresectable, metastatic melanoma who have progressed after checkpoint inhibitor therapy.
This is a landmark study—potentially the first head-to-head trial comparing a TCR-T cell therapy against standard treatment options in solid tumors including TIL cellular therapy. Eligible patients include those who’ve previously received PD-1-based immunotherapy (e.g., pembrolizumab, nivolumab).
Primary endpoint: Progression-free survival
Secondary endpoints: Overall survival, response rate, safety, and quality of life
What This Means for the Field
Cell therapy is no longer just for hematologic cancers. We’re seeing a paradigm shift in how we approach solid tumors—offering one-time, living therapies that can potentially yield durable responses in even the most treatment-refractory cases.
If IMA203 continues to deliver, its implications go far beyond melanoma. Given PRAME’s broad expression, this therapy could soon expand into other PRAME expressing solid tumors—like uterine cancers, sarcomas, and triple-negative breast cancers.
As this space evolves, trials like SUPRAME will be critical not just in validating efficacy, but in helping us understand how to best integrate TCR therapies alongside existing options like checkpoint inhibitors, targeted therapies, and intratumoral agents like RP1 soon to be FDA approved!
This is a pivotal moment for solid tumor cell therapy. IMA203 already signals a bright future for PRAME-targeted immunotherapy. For clinicians, patients, and institutions eager to participate, this trial represents a real opportunity to be part of a game-changing advance. I’m personally excited about this direction. I hope to bring this trials like this to my future practice and be part of the effort to expand the role of cellular therapies in solid tumor oncology.
About the author
Dr. Sajeve Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. He brings a wealth of expertise to the complex and challenging world of oncology.
Disclosures:
Dr. Thomas serves as a speaker for Bristol Myers Squibb (BMS), Merck, Ipsen, Natera, Immunocore, Pfizer, and SpringWorks. He also receives industry grants in support of numerous clinical trials.