NEW YORK – Following positive data from a Phase Ib clinical trial, Immatics is moving its T-cell receptor (TCR) therapy IMA203 into a Phase III, registration-directed study.
The firm announced data from the Phase Ib trial of IMA203 in patients with metastatic melanoma whose tumors haven't responded to PD-1-targeted immunotherapy. Immatics Chief Medical Officer Cedrik Britten presented updated results from the trial during a conference call on Thursday.
To be eligible for the trial, patients had to test positive for HLA-A*202 and the tumor antigen PRAME. The basket trial was open to patients with any type of solid tumor meeting these biomarker criteria, though Britten focused his presentation on the data from the efficacy-evaluable cohort of melanoma patients treated with IMA203.
After patients underwent central lab testing to determine their HLA status, as well as testing with Immatics' IMADetect messenger RNA assay to confirm PRAME expression, they had their cells harvested through leukapheresis. Then, Immatics produced the patient-specific therapeutic product within a 14-day manufacturing time, which directs CD8 and CD4 T cells to kill patients' tumor cells by arming those T cells with a PRAME-directed T-cell receptor that binds to the PRAME presented on the cancer cells. Patients received lymphodepleting chemotherapy prior to the infusion of their bespoke IMA203 product, then a low dose of interleukin-2.
Among 28 melanoma patients treated with IMA203 in the dose-expansion phase of the trial, the confirmed objective response rate was 54 percent, and seven out of 14 patients' responses were ongoing at the time of data cutoff. The median duration of response was 12.1 months, and the median progression-free survival was six months. The median overall survival wasn't reached at the time of the data cutoff, Britten said.
Twelve patients experienced what Britten called "remarkably deep" tumor responses, with their target tumor lesions shrinking by more than 50 percent.
Although this wasn't a randomized trial, and therefore didn't have a comparator arm, Britten shared data from the initial 11-patient dose-escalation cohort as a point of comparison for the dose-expansion melanoma cohort.
Among patients in the initial dose-escalation cohort who received a lower dose of the IMA203 T-cell receptor therapy than patients in the efficacy-evaluable dose-expansion cohort, the progression-free survival and overall survival results were significantly lower. Patients on the lower dose lived for a median of 6.3 months overall and for a median of 2.6 months without their tumors progressing.
"These data highlight the potential of IMA203, given at relevant doses, to achieve long-lasting anti-tumor effects in melanoma patients," Britten said, adding that among the patients who received the higher doses, the T cells persisted in patients' blood for a longer period.
In a larger, efficacy-evaluable cohort that included 70 patients with any tumor type, Britten said that IMA203's tolerability profile was generally acceptable. Eleven percent of patients experienced grade 3 or higher cytokine release syndrome, and there were no treatment-related deaths.
After discussing these data with the US Food and Drug Administration as well as Germany's regulatory agency, the Paul-Ehrlich-Institut, Immatics is moving into a randomized Phase III trial, dubbed SUPRAME.
The firm finalized the trial design and endpoints during meetings with regulators. The trial is expected to enroll 360 patients with unresectable or metastatic melanoma who've already been treated with an immune checkpoint inhibitor. Immatics will randomize these patients to receive either IMA203 or the investigator's choice of approved melanoma treatment for second-line or later settings.
Immatics will have to show that IMA203 significantly improves median progression-free survival, the Phase III trial's primary endpoint, compared to the control arm in order to gain full market approval for the drug.
"We believe this to be the quickest path toward seeking full approval in this patient population," Britten said, adding that the firm expects the median progression-free survival endpoint to read out earlier than objective response rate. "Median progression-free survival [also] provides clinical benefit … which we believe allows for a more attractive commercial position for this drug."
Immatics is on track to launch the Phase III SUPRAME trial in December of this year and to complete full enrollment by late 2026. The firm will conduct a planned interim analysis once 200 patients have enrolled in the trial.
"It's becoming increasingly clear that targeting PRAME with Immatics' IMA203 TCR T-cell therapy has the potential to offer durable benefits with advanced-stage melanoma patients while maintaining a well-manageable tolerability profile," Britten said.