PRAME-Targeted Agent Shows Activity in Pretreated Metastatic Melanoma

“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," according to study author Martin Wermke, MD.

Treatment with IMA203, an investigational T-cell therapy targeting preferentially expressed antigen in melanoma (PRAME), demonstrated clinical activity among a small cohort of patients with previously treated metastatic melanoma, according to a presentation on data from a phase 1 trial (NCT03686124).¹

Findings highlighted at the 2024 Society for Melanoma Research Congress showed a confirmed objective response rate (ORR) of 54% (n = 14/26) and a median duration of response (DOR) of 12.1 months (range, 4.2 to 25.5+). Of note, 7 of 14 patients with a confirmed response had ongoing responses at the time of the analysis.

During the dose-escalation portion of the trial, data showed a median progression-free survival (PFS) of 2.6 months and a median overall survival (OS) of 6.3 months. In the dose-expansion portion of the trial, IMA203 produced a median PFS of 6.0 months (range, 0.3+ to 26.8+); the median OS was not reached (NR; range, 0.3+ to 26.8+). Investigators noted a significant shift in PFS (P <.0001) and OS outcomes (P = .0003) across the melanoma cohort between the dose-escalation and dose-expansion phases. Additionally, among patients who received treatment in the dose-expansion portion and had a 50% or greater reduction in tumor size, the median PFS was 13.4 months.

Across 70 patients in the total safety population, cytopenias associated with lymphodepletion were the most common type of toxicity. Additionally, investigators reported cytokine release syndrome of grade 1 (37%; n = 26/70), grade 2 (46%; n = 32/70), and grade 3 (11%; n = 8/70). Rates of immune effector cell-associated neurotoxicity (ICANS) were 6% at grade 1, 4% at grade 2, and 4% at grade 3. There were no deaths associated with the study treatment.

Overall, investigators noted that the tolerability of IMA203 among patients with melanoma in the trial was usually comparable with prior reports of the agent’s full monotherapy safety profile. The recommended phase 2 dose was identified as 1 x 10⁹ to 10 x 10⁹ TCR-T cells.

“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 [who] have all exhausted multiple lines of systemic treatments illustrates the impact IMA203 can have on [patients with] metastatic melanoma,” presenting study investigator Martin Wermke, MD, of National Center for Tumor Diseases Dresden, said in a press release on these findings.² “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.”

With a data cutoff of August 23, 2024, the study included a total of 11 patients with melanoma in the phase 1a dose-escalation portion and a total of 28 patients with melanoma who were evaluable for efficacy in the phase 1b dose-expansion portion.

Investigators plan to further evaluate treatment with IMA203 as part of the registration-enabling, randomized phase 3 SUPRAME trial, which is expected to launch in December 2024. In the SUPRAME trial, an expected population of 360 patients with unresectable or metastatic melanoma following prior treatment with a checkpoint inhibitor will be randomly assigned 1:1 to receive IMA203 (n = 180) or investigator’s choice of selected approved agents (n = 180).

The trial’s primary end point will be PFS. Secondary end points include safety, ORR, DOR, OS, and patient-reported outcomes.

Investigators anticipate a pre-specified interim analysis after approximately 200 patients enroll on the SUPRAME trial. Additionally, the completion of patient enrollment is expected by late 2026.

References

1. ACTengine® IMA203 TCR-T targeting PRAME in PD1 refractory metastatic melanoma - phase 1b dose expansion clinical data update. Immatics. October 10, 2024. Accessed October 14, 2024. https://tinyurl.com/336mae8t
2. 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. October 10, 2024. Accessed October 14, 2024. https://tinyurl.com/7pp9vf9f