Study of CAR T-cell therapy rese-cel in scleroderma enrolling in US
Clinical trial will enroll patients with skin and heart, lung, kidney involvement
A Phase 1/2 trial testing Cabaletta Bio’s CAR T-cell therapy, rese-cel (resecabtagene autoleucel), in adults with hard-to-treat systemic sclerosis (SSc) is recruiting patients at several sites in the U.S.
The open-label RESET-SSc trial (NCT06328777) is assessing the safety and efficacy of rese-cel as a single infusion into a vein, or intravenously, in patients ages 18-75. It plans to enroll two groups of patients, one with severe skin involvement and the other with heart, lung, and/or kidney involvement, with or without skin manifestations.
SSc, also named scleroderma, is marked by inflammation and fibrosis, or scar tissue accumulating in the skin and possibly the internal organs. Hyperactive B-cells drive the inflammatory attacks by producing antibodies that damage healthy tissues.
Rese-cel, formerly CABA-201, involves collecting a patient’s immune T-cells and modifying them to carry a chimeric antigen receptor (CAR) that targets CD19, a protein on the surface of B-cells. The CAR also contains 4-1BB, a protein domain involved in T-cell survival and activation. The modified T-cells are infused back into the patient, where they should deplete B-cells.
Cabaletta is running several RESET Phase 1/2 studies in autoimmune diseases. RESET-SSc’s main goal is to assess rese-cel’s safety for up to 28 days after an infusion by examining side effects’ occurrence and severity. Secondary outcomes, assessed for up to three years, include evaluating changes in vital signs and studying the therapy’s pharmacological properties. The researchers will also determine its efficacy by analyzing the proportion of patients who achieve Combined Response Index in Diffuse Cutaneous Systemic Sclerosis (CRISS) criteria of disease severity.
Improvements with rese-cel
Preliminary data from the RESET-SSc study showed the treatment led to clinically meaningful skin improvements three months after an infusion in the first patient with severe skin involvement. These improvements were seen in several areas, along with with better lung function. The participant had discontinued all disease-specific therapies.
“Since presenting clinical and translational data from the RESET program demonstrating that a single weight-based dose of rese-cel was able to provide potentially transformative clinical responses after discontinuation of all immunosuppressants and while off or tapering off steroids, we have seen robust physician and patient interest in the RESET clinical program,” Steven Nichtberger, MD, Cabaletta’s CEO, said in a company press release.
Last February, the company learned that a patient who reported a fever three days before rese-cel infusion was dosed without informing the trial’s medical monitor, as required by its protocol.
Nine days after the infusion, the patient had immune effector cell-associated neurotoxicity syndrome (ICANS), which affects the brain and spinal cord and may occur after certain immunotherapies. The patient experienced temporary confusion, but the event was not deemed to be immediately life-threatening. The episode resolved with corticosteroid treatment and the patient was discharged without further symptoms.
After a review by the trial’s independent data monitoring committee, the study was allowed to proceed at the current dose, with the requirement that investigators must write to the company confirming the absence of fever or signs of infection two weeks before an infusion.
According to Cabaletta, results from the first 10 patients dosed with rese-cel across multiple autoimmune diseases showed “compelling clinical efficacy with a favorable safety profile and deep B-cell depletion.” Additional data is anticipated at the upcoming EULAR 2025 Congress in Barcelona, in June.
Last year, the FDA granted orphan drug designation to rese-cel for adults with hard-to-treat SSc. The designation is meant to accelerate the development of therapies for rare diseases, or those that affect fewer than 200,000 people in the U.S.
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