TCR-T Therapy Yields Clinical Responses Across Tumor Types

IMA203, Immatics’ PRAME-targeted ACTenginecell therapy, has demonstrated clinical responses as a monotherapy in multiple forms of solid tumors, according to new data from a phase 1 dose-escalation trial (NCT03686124).

The ACTengine technology, as the company terms it, uses an autologous T cell receptor (TCR)-engineered cell approach. Immatics’ platform uses a proprietary manufacturing process and XCEPTOR platformdesigned to enhance T cell engraftment and persistence in vivo. 

The updated data is from 27 patients in phase 1a and the first 5 in phase 1b. Investigators found that confirmed objective response rate (ORR) was 50% (n = 6) at the target dose or higher (at least 1 billion infused cells) and 80% (n = 4) in phase 1b patients. These responses were seen across patients’ tumor types, which included cutaneous melanoma, ovarian cancer, head and neck cancer, uveal melanoma, and synovial sarcoma. Investigators also found positive findings in T cell engraftment, persistence, and tumor infiltration.

“The data presented today highlight the clinical potential of PRAME as one of the most promising multi-tumor targets to achieve meaningful benefits for a large cancer patient population,” Cedrik Britten, MD, chief medical officer,Immatics, said in a statement. “In addition to this first data from IMA203 monotherapy today, we are awaiting data from 2 additional dose expansion cohorts: IMA203 together with an immune checkpoint inhibitor and our 2nd generation product candidate IMA203CD8.

READ MORE: Improving Outcomes in Solid Tumors With Personalized Cell Therapies

IMA203 has demonstrated a manageable safety profile. All patients had cytopenia of grades 1 to 4 associated with lymphodepletion. Most patients (97%) had cytokine release syndrome (CRS) of any grade, with 29 experiencing low-grade CRS (grade 1/2) and the other 2 experiencing grade 3 CRS which downgraded after a few days. Five patients (16%) had low-to-moderate (grade 1/2) immune effector cell associated neurotoxicity syndrome (ICANS). There were no dose-dependent increases of CRS or ICANS observed and no additional dose limiting toxicities have been observed since initial data were announced in March 2021.

The updated data is from phase 1a and 1b of the trial. Differences between these phases include higher cell doses, manufacturing enhancements, and lower enrollment of very heavily pre-treated patients with extreme tumor burden. An outcome endpoint is also shifting from initial objective response rate (ORR) at 6 weeks to confirmed ORR at 12 weeks.

Specifically, in the phase 1a group, initial ORR was 48% (n = 13) at 6 weeks and confirmed ORR was 19% (n = 5) at 12 weeks. Out of the 7 patients at dose level 4, receiving over 1 billion cells, initial ORR was 57% (n = 4) and confirmed ORR was 29% (n = 2). This dose has been chosen as the provisional recommended phase 2 dose. Patients in phase 1a had a mean of 4.2 lines of prior therapies and a high baseline tumor burden.

In cohort 1 of phase 1b, all objective responses at week 6 were confirmed at week 12 (80%; n = 4). These patients were also heavily pretreated, with a mean 4.0 lines of prior therapies and a moderate-to-high baseline tumor burden.

“As we continue to shift our focus from Phase 1a to Phase 1b, we look forward to reporting meaningful data throughout 2023, including safety and response rates, as well as durability of response with a longer follow-up time. In addition, we are excited to start a first-in-human trial with our half-life extended Bispecific against PRAME, TCER® IMA402, also in 2023,” Britten added.

The phase 1b study is also evaluating IMA203 in combination with nivolumab as well as IMA203 co-transduced with a CD8αβ co-receptor to make the next-generation therapy IMA203CD8. More data from these cohorts will be announced in 2023.

REFERENCE

Immatics reports interim clinical data update on ACTengine® IMA203 TCR-T monotherapy targeting PRAME. News release. Immatics. October 10, 2022. https://www.globenewswire.com/news-release/2022/10/10/2530925/0/en/Immatics-Reports-Interim-Clinical-Data-Update-on-ACTengine-IMA203-TCR-T-Monotherapy-Targeting-PRAME.html