Improving Outcomes in Solid Tumors With Personalized Cell Therapies

IMA203, an autologous, TCR-engineered T cell (TCR-T), PRAME-directed therapy from Immatics has demonstrated efficacy across multiple types of solid cancers, according to data from the IMA203 phase 1 trial (NCT03686124).^1,2 The personalized cell therapy is developed using Immatics’ ACTengine.

These data, based on 16 heavily pre-treated patients in the IMA203 trial, were presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), November 10-14, 2021, by investigator Martin Wermke, MD, University Hospital Dresden.

Investigators found that all 12 evaluable patients achieved disease control, defined as stable disease (SD) or a partial response (PR), with 6 patients demonstrated PRs according to RECIST1.1. The therapy had an acceptable safety profile, with only transient and manageable treatment-emergent adverse events (AEs). 

GeneTherapyLive spoke with Cedrik Britten, MD, chief medical officer, Immatics, to learn more about IMA203 and what differentiates the candidate from other cell therapies. He also discussed how IMA203 could improve outcomes in patients with solid tumors.

GeneTherapyLive: How does IMA203 compare to other cell therapies and what are its advantages in solid tumors?

Cedrik Britten, MD: While other cell therapies mostly focus on improving the interaction of the T cell with the tumor cell and can only target peptides present on the cell surface, Immatics has established a screening technology that is able to identify tumor-specific peptides derived from proteins within the cancer cell. This increases the cancer target space by approximately 300%. After identification and validation of the cancer target, Immaticsis able to engineer T cells designed to specifically target and destroy these tumor cells. Combining screening for the right targets and modification of the T cell maximizes specificity and efficacy of our therapeutic approach.

For the cell therapy approach with IMA203, Immatics is utilizing TCR-T cells optimized for targeting a peptide called PRAME. This target has been identified and characterized by Immatics’ proprietary mass spectrometry-based discovery platform, XPRESIDENT®.

Factors that differentiate IMA203

• Selected PRAME which is a clean target that is prevalently and homogenously expressed across many cancers
• Selected a peptide with high copy number expressed per tumor cell
• Designed and engineered TCR that has optimized affinity
• Manufacturing process with only 7 days ex vivo expansion resulting into younger and thus fitter T cells

PRAME is homogenously expressed and highly prevalent across several solid cancer indications which makes it a very attractive target and increases the applicability of this therapeutic approach in a wide range of solid tumors as well as a broad patient population. 

How could IMA203, if approved in the future, improve the treatment landscape for solid tumors?

Immunotherapies like CAR-T-cell therapies have fundamentally changed the therapeutic landscape to treat hematological malignancies. However, their clinical efficacy in solid tumors has been limited due to the lack of highly tumor selective targets. With our proprietary target identification platform, we can identify peptides derived from proteins expressed from within the cancer cell and to a much lower extent in normal cells, which expands the number of potential targets on solid tumors significantly. With IMA203, our engineered T cells are designed to specifically target and attack solid tumors.

With IMA203, we may offer a new therapeutic approach where a one-off treatment may lead to long-term disease control for a high fraction of infused patients at an acceptable safety profile. If successful, IMA203 treatment could be made available for many patients with advanced cancer for multiple rare and common cancers. High impact for many patients and even reach earlier treatment lines over time where it coldreplace the current standard of care (SOC).

We are clearly in the early stages of our clinical development and as you know it’s a long road to approval. We continue to evaluate IMA203 and look forward to announcing further data from the program in the future.

Transcript edited for clarity.

REFERENCES

1. Wermke M, Tsimberidou AM, Mohamed A, et al. Safety and anti-tumor activity of TCR-engineered autologous, PRAME-directed T cells across multiple advanced solid cancers at low doses – clinical update on the ACTengine® IMA203 trial. Presented at: 2021 SITC Annual Meeting; November 10-14, 2021; Washington, DC. Abstract 959
2. Immatics reports clinical responses across multiple solid tumor types in ongoing ACTengine® IMA203 phase 1a trial targeting PRAME. News release. Immatics. November 9, 2021. https://investors.immatics.com/news-releases/news-release-details/immatics-reports-clinical-responses-across-multiple-solid-0