TOPLINE:

A form of T-cell therapy targeting a highly expressed antigen in uveal melanoma, a rare form of the disease, appears to be tolerable and efficacious, even though the tumors are considered to be immunologically cold, showed early-phase trial data presented at European Society for Medical Oncology (ESMO) Annual Meeting 2025.

METHODOLOGY:

• Uveal melanoma is the most common tumor of the adult eye, at a worldwide incidence of 0.6-0.7 per 100,000.
• Although there have been more than 20 FDA approvals for novel melanoma drugs over the past 15 years, only two have demonstrated efficacy in rare subtypes, such as uveal disease.
• Anzutresgene autoleucel, also known as anzu-cel (IMA203), is a T-cell receptor-based therapy that targets preferentially expressed antigen in melanoma (PRAME), which is expressed in 90% of patients with uveal melanoma. After PRAME testing, patients undergo leukapheresis, followed by anzu-cel manufacturing over a 2-week period, followed by a conditioning regimen of lymphodepleting chemotherapy. Then there is a one-time infusion of anzu-cel, supported by 10 days of low dose interleukin-2.
• ACTengine is an ongoing phase 1/2 of anzu-cel in patients with advanced and/or metastatic solid tumors expressing PRAME, including 16 patients with uveal melanoma, who had a median age of 62 years and had previously received a median of two lines of therapy.

TAKEAWAY:

• As expected, almost all (94%) of the patients experienced treatment-emergent cytopenia associated with the lymphodepletion. In addition, every patient had cytokine-release syndrome, which was, again, as expected, with 82% of cases grade 1-2. No grade 5 anzu-cel-related events were observed.
• The confirmed objective responses rate was 67%, and the disease control rate was 88%. The median duration of response was 11.0 months.
• After a median follow-up of 10.4 months, the median progression-free survival with anzu-cel was 8.5 months, with 39% of patients progression-free at 12 months.
• After a median survival follow-up of 14.3 months, the median overall survival was not reached. At 12 months, 71% of patients were still alive.

IN PRACTICE:

“Our takeaway is that targeting a highly expressed antigen, in this case PRAME, with T-cell receptor-specific T cells, even in [an immunologically] cold tumor like uveal melanoma, can result in clinical activity, and this can be taken forward in other areas of oncology,” said study presenter.

“These results are being verified in a phase 2 extension cohort in uveal melanoma,” she said.

SOURCE:

This study was presented at ESMO 2025 on October 20 by Sapna Patel, MD, visiting professor, medicine-medical oncology at University of Colorado Anschutz Medical Campus, Aurora, Colorado.

LIMITATIONS:

Study discussant John Haanen, MD, PhD, head of the Division of Medical Oncology, Netherlands Cancer Institute, Amsterdam, Netherlands, pointed out that as the study has a relatively small number of participants, there is a question mark over whether the safety outcomes would change if more patients were treated.

He said that the responses with anzu-cel appear durable, but that they will need to be confirmed in a larger phase 2 study, and the issue of access to such treatment in non-White populations will need to be addressed.

DISCLOSURES:

This study was funded by Immatics NV.

Patel declared relationships with TriSalus, Novartis, BMS, Cardinal Health, IO Biotech, Pfizer, OncoSec, Scancell, Vindico Medical, MSD, Ideaya, Replimune, Veda Trials, Natera, Provectus Biopharmaceuticals, Lyvgen, InxMed, Foghorn Therapeutics, Seagen, and Syntrix Bio.

Haanen declared relationships with BioNTech US, Bristol Myers Squibb, Novartis AG, Amgen, Sāstra, Asher Bio, Neogene Therapeutics, Agenus, AZ, CureVac, Eisai, GSK, Imcyse, Intellia, Iovance Bio, Immunocore, Ipsen, Medigene, Merck Serono, MSD, Molecular Partners, Orgenesis, Pfizer, Roche/Genentech, Sanofi, Third Rock Ventures, Achilles Tx, EverImmune, Instil Bio, and T-Knife.