No further DLTs occurred in the RP2D range with dexamethasone premedication. These findings show that the bispecific TCER platform has a manageable safety profile with mostly transient adverse events and promising antitumor activity at the RP2D of IMA401 with or without pembrolizumab. ClinicalTrials.gov identifier: NCT05359445 .

P1, N=9, Recruiting, Zelluna Immunotherapy AS

P1, N=38, Not yet recruiting, Marker Therapeutics, Inc. | Trial completion date: Dec 2027 --> Sep 2028 | Trial primary completion date: Sep 2027 --> Jul 2028

The recent US FDA approvals of lifileucel (a TIL therapy for advanced melanoma) and afamitresgene autoleucel (a TCR therapy targeting MAGE-A4 in synovial sarcoma) mark the first regulatory recognition of cell therapies for solid tumours and signal a new era for oncology...Emphasis is placed on emerging innovations like gene-edited and allogeneic therapies, as well as future directions for integrating cell therapies into mainstream oncology. We conclude with recommendations for overcoming barriers related to cost, toxicity management, and equitable access across Europe.

P1, N=95, Active, not recruiting, Immatics Biotechnologies GmbH | Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2025 --> Mar 2026

P1, N=320, Recruiting, BioNTech SE | N=156 --> 320

P1, N=120, Active, not recruiting, USWM CT, LLC | Trial primary completion date: Apr 2026 --> Dec 2026

P1, N=120, Active, not recruiting, USWM CT, LLC | Trial primary completion date: Dec 2025 --> Apr 2026

This constituted only the second approval of a cell therapy in a solid tumor following lifileucel in melanoma and demonstrated the potential of cell therapies in sarcomas...However, the broader application of these therapies is hindered by the lack of targetable sarcoma-restricted immunogenic epitopes, spatiotemporal intratumoral heterogeneity, and a profoundly immunosuppressive tumor microenvironment that impedes effector-cell trafficking, expansion and persistence. While cell therapies hold promise for integration into precision medicine approaches for sarcomas, their successful implementation will require careful evaluation of clinical feasibility, logistical considerations and cost-effectiveness to optimize patient outcomes.

Lastly, TCR-NKs are not activated when co-cultured with normal cells, displaying a safe profile. Combining the innate cytotoxicity of NKs with MAGE-A4-specific targeting of an affinity-enhanced TCR, results in a potent and safe cellular product representing a promising and novel therapeutic off-the-shelf paradigm for the treatment of many solid cancers.

However, challenges remain regarding HLA restriction, tumor microenvironment resistance, manufacturing delays and cost. Future efforts should focus on broadening applicability, optimizing combinations, and ensuring equitable access.

P1/2, N=37, Completed, Baylor College of Medicine | Trial completion date: May 2027 --> Jul 2025 | Active, not recruiting --> Completed