IMA203 Displays Efficacy in Heavily Pretreated Melanoma

IMA203, a TCR-T agent targeting PRAME, was active and offered meaningful progression-free survival (PFS) and overall survival (OS) outcomes in patients with heavily pretreated melanoma, according to updated data from a phase 1b study (NCT03686124) provided by Immatics NV.¹

At the April 25, 2024, data cutoff, all patients with melanoma who received IMA203 (n = 28) achieved a confirmed objective response rate (ORR) of 54% and an unconfirmed ORR of 62% with a median duration of response (DOR) of 12.1 months. The disease control and tumor shrinkage rates were 92% and 88%, respectively. The median PFS and OS were 6.0 months and not reached, respectively.

In patients with cutaneous melanoma (n = 13), the confirmed ORR and unconfirmed ORR were also 54% and 62%, respectively, with a median DOR of 12.1 months. The disease control and tumor shrinkage rates were 92% and 85%, respectively. The median PFS was 6.1 months, and the median OS was 15.9 months.

Full data from the ongoing phase 1b study will be presented on October 11, 2024, during the Society for Melanoma Research Congress 2024.

In terms of safety, the most frequently reported adverse effects (AEs) in the IMA203 monotherapy safety population in phase 1a/b (n = 70) were grade 1 to 4 cytopenias that were determined to be associated with lymphodepletion and predominately mild to moderate cytokine release syndrome. No grade 5 AEs were reported. Immune effector cell–associated neurotoxicity syndrome was also reported at grade 1 (6%), grade 2 (4%), and grade 3 (4%) severity. Investigators noted that the full IMA203 monotherapy tolerability profile was consistent with that of the phase 1b melanoma subset.

Immatics also announced that, based on the data from the phase 1b study, the phase 3 SUPRAME trial will commence in December 2024. SUPRAME will examine IMA203 vs investigator’s choice of therapy in approximately 360 patients with second-line or later unresectable or metastatic melanoma who have received prior treatment with an immune checkpoint inhibitor and have HLA-A*02:01–positive disease. A prespecified interim analysis of the study is planned for early 2026, with full enrollment expected to be completed later in 2026.

“Observing significant tumor shrinkage and durable responses combined with meaningful PFS and OS outcomes after a single treatment with ACTengine® IMA203 in this patient population that have all exhausted multiple lines of systemic treatments illustrates the impact IMA203 can have on metastatic melanoma patients,” Martin Wermke, MD, head, the Early Clinical Trial Unit, the National Center for Tumor Diseases Dresden, the University Hospital Carl Gustav Carus Dresden, the Technical University of Dresden, in Germany, as well as the coordinating investigator of the ACTengine® IMA203 TCR-T trial, stated in a news release. “These results now affirm the therapeutic potential of IMA203 and provide a strong rationale for the expedited late-stage clinical development of this product candidate.”

The phase 1b study enrolled patients with recurrent/refractory solid tumors who received or were not eligible for all available indicated standard-of-care treatments. Eligibility criteria included an ECOG performance status of 0 or 1, an HLA phenotype positive for the study, measurable disease by RECIST 1.1 criteria, adequate organ function, and a life expectancy of more than 5 months.²

The coprimary end points were safety and tolerability, and determining the maximum tolerated dose and the recommended dose for expansion. Secondary end points included tumor response and T-cell persistence.

The melanoma subset that was included in the data update consisted of patients with cutaneous melanoma (n = 13), uveal melanoma (n = 12), mucosal melanoma (n = 2), and melanoma of unknown primary (n = 1). The treated population underwent a median of 2 prior lines of systemic therapy.¹

Additional data from phase 1b demonstrated that IMA203 T-cell dose was significantly associated with confirmed clinical responses (P = .02). Additionally, IMA203 T-cell dose was correlated with T-cell peak level (c_max, r = 0.84, P = 1.6 x 10^-18) and IMA203 T-cell peak level (c_max, P = .05) and T-cell exposure (AUC_0-28d, P = .05) were associated with confirmed clinical responses. Investigators noted that all patients in phase 1b received an updated version of IMA203 that utilized a T-cell enrichment process via monocyte depletion or CD8/CD4-positive selection.

SUPRAME will be a global study with sites in the United States (US) and Europe. The study will use median PFS as the primary end point to support potential full approval; secondary end points will include ORR, safety, DOR, OS, and patient-reported outcomes. The initial goal of the study is biologics license application (BLA) approval in the US; Immatics is planning to submit a BLA to the FDA in early 2027.

“We are enthusiastic about the clinical data as they confirm our conviction in the durability and long-term efficacy of ACTengine IMA203, demonstrated by the favorable median PFS for patients in the dose-expansion cohort. I would like to highlight that a subgroup of 12 out of 26 patients showed more than 50% reduction of tumor lesions and a median PFS of 13.4 months,” Cedrik Britten, MD, chief medical officer at Immatics, added in the news release. “We believe the presentation of this data set in conjunction with our recent meeting with the FDA, which has resulted in a pivotal trial design with PFS as the primary end point for full approval, positions us to advance the development of IMA203 in the second-line or later metastatic melanoma setting.”

References

1. Immatics announces updated phase 1b clinical data on ACTengine IMA203 TCR-T targeting PRAME in melanoma patients and provides update on upcoming SUPRAME phase 3 trial. News release. Immatics NV. October 10, 2024. Accessed October 10, 2024. https://investors.immatics.com/news-releases/news-release-details/immatics-announces-updated-phase-1b-clinical-data-actenginer
2. ACTengine IMA203/​IMA203CD8 as monotherapy or in combination with nivolumab in recurrent and/​or refractory solid tumors (ACTengine). ClinicalTrials.gov. Updated August 29, 2024. Accessed October 10, 2024. https://clinicaltrials.gov/study/NCT03686124