In an interview with Targeted Oncology, Jason Luke, MD, FACP, associate director for clinical research at the Hillman Cancer Center at the University of Pittsburgh, discusses the phase 1 study assessing IMA203, an autologous TCR-T (T-cell receptor-engineered T-cell) therapy, in patients with relapsed unresected or metastatic melanoma.
IMA203 demonstrated an overall favorable tolerability profile. The most common treatment-emergent adverse events (TEAEs) were chemotherapy-related cytopenias (100% of patients), which are expected due to the lymphodepletion. Mild to moderate cytokine release syndrome (CRS) was observed in 83% (grade 1–2) and 11% (grade 3) of patients. Infrequent cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported (6% grade 1, 4% grade 2, 4% grade 3). Importantly, no grade 5 events were observed.
Objective responses were observed in several solid tumor types, including melanoma, ovarian cancer, and synovial sarcoma. In heavily pretreated patients with melanoma (median 2 prior systemic therapies) at the recommended phase 2 dose (RP2D), the confirmed objective response rate (cORR) was 54% (n = 14/26), with tumor shrinkage observed in 88% (n = 23/26). The median duration of response (DOR) was 12.1 months, with 7 of 14 confirmed responses still ongoing for over 2 years. The median -progression-free survival (PFS) was 6 months, and the median overall survival (OS) was not reached at 8.6 months of median follow-up. Higher doses of IMA203 were associated with a higher rate of confirmed responses, and higher concentrations of IMA203 TCR-T cells in the periphery correlated with improved clinical efficacy.
Successful trafficking of IMA203 cells to various organs was observed. This was evidenced by their ability to shrink metastatic tumor lesions in a wide range of locations, including the lung, liver, pleura, peritoneum, skin, lymph nodes, adrenal gland, bladder, kidney, spleen, and muscle.
Given its promising risk/benefit profile and the high prevalence of PRAME in melanoma, a registration-directed phase 3 trial, named SUPRAME (NCT06743126), is currently underway. This trial will further evaluate the efficacy of IMA203 in patients with previously treated (second-line) advanced cutaneous melanoma, aiming for potential regulatory approval.