Improving Personalized Cell Therapies for Solid Tumors

Immatics’ IMA203, an autologous, TCR-engineered T cell (TCR-T), PRAME-directed therapy seems efficacious across multiple types of solid cancers, according to data from the IMA203 phase 1 trial (NCT03686124).^1,2

Data from the trial, which has dosed 16 heavily pre-treated patients across dose levels as of August 15, 2021, 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.

IMA203 seemed to be well-tolerated, with only transient and manageable treatment-emergent adverse events (AEs). In terms of efficacy, 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.

Cell&GeneLive spoke with Cedrik Britten, MD, chief medical officer, Immatics, to learn more about IMA203 and the data presented at SITC 2021. He also discussed the advantages of the ACTengline and ACTallo platforms used in developing the therapy.

Cell&GeneLive: Can you give me an overview of the positive data presented at SITC?

Cedrik Britten, MD: At SITC we presented the latest update from our ongoing clinical trial with IMA203, a product candidate from our ACTengine® series, which is being evaluated in advanced solid tumor patients. The trial is a Phase 1a dose escalation study and we have now analyzed data from patients treated with the first three of four dose levels. We are excited that we could show a high preliminary objective response rate at doses below 1 billion total transduced CD8 T cells, which is a dose that is below a threshold where we expected to see initial activity and below our target dose. IMA203 continues to show high levels of T cell engraftment, persistence, and tumor infiltration at these first three dose levels. For 94% of patients treated with IMA203 we achieved disease control and 88% of patients showed tumor shrinkage. Objective response rates were observed in 50% of patients across multiple solid cancer types which is very encouraging data for heavily pre-treated patients at doses below the target dose level.

Can you tell me about the ACTengine and ACTallo platforms and their advantages in creating cell therapies?

ACTengine® is a personalized approach for patients with advanced solid tumors. The patient’s own T cells are genetically engineered to express a novel, proprietary T cell receptor directed against a defined cancer target. The modified T cells are then reinfused into the patient to attack the tumor, an approach also known as TCR-T. Immatics is further advancing the adoptive cell therapy (ACT) approach beyond individualized manufacturing with its product class, ACTallo®. ACTallo® is a process to manufacture allogeneic, off-the-shelf, TCR-engineered cellular therapies derived from healthy donors’ gamma delta T cells. Using healthy donor T cells circumvents the need to use T cells from heavily pre-treated or aging cancer patients. In addition, products are available immediately for patient treatment upon enrollment without any delays for individualized manufacturing. Off-the-shelf products are readily available and thus may even reach more patients that do not have the time to wait for an autologous product. Next to the increased reach into larger patient populations, ACTallo may be supplied at much reduced cost of goods and may lend itself to repeat dosing approaches.

What are next steps/further research for IMA203?

Based on the promising preliminary results, Immatics plans to expand the IMA203 study to three study cohorts. These will include IMA203 as a monotherapy, IMA203 in combination with an immune checkpoint inhibitor and a second generation approach in which IMA203 cells are co-transduced with a CD8 co-receptor, called IMA203CD8. Each of these three cohorts could trigger further clinical development in selected tumors of special interest in separate cohorts. Selected tumors of special interest could trigger entry to late-stage clinical development with either fast path to filing or early access to significant patient populations with high unmet medical need.

Right now, Immatics is enrolling patients to the 4th and highest dose level which means up to 2.5 billion total transduced cells for the ACTengine® IMA203 trial. We look forward to providing updates on these clinical outcomes in 2022.

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