Phase 1 trial of KYV-101 opening in progressive MS without relapses

Researchers at Stanford University have partnered with Kyverna Therapeutics to conduct an investigator-initiated clinical trial of the company’s cell-based therapy, KYV-101, in people with progressive forms of multiple sclerosis (MS) without relapses.

The open-label Phase 1 trial (NCT06138132) will take place at the Stanford Multiple Sclerosis Center in Palo Alto, California. It is expected to enroll up to 12 people, ages 18 to 55, with primary progressive MS (PPMS) or secondary progressive MS (SPMS) who have not experienced recent relapses.

It either has started recruiting eligible MS patients or is expected to open soon.

All will receive a single dose of the CAR T-cell therapy and be followed for up to one year. The study’s main goal is to determine if the therapy is safe and tolerable, and to determine the dose with the best safety and potential efficacy profile.

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Safety and feasibility clinical trial in progressive MS patients

“This phase 1 trial is a first-in-human study that will assess safety, feasibility, and tolerance in patients with non-relapsing multiple sclerosis for which there is no proven treatment,” Jeffrey Dunn, MD, a clinical professor of neurology at Stanford and the trial’s principal investigator, said in a company press release.

“We foresee great therapeutic potential for CAR T-cell therapy for immune-mediated disease of the nervous system,” Dunn added.

Collaborative studies also will be conducted into how certain disease biomarkers change after KYV-101’s infusion, with researchers aiming to define predictors of response and the investigative treatment’s potential for reprogramming a patient’s immune system.

MS is marked by mistaken immune system attacks that damage healthy parts of the brain and spinal cord, leading to nerve cell degeneration and disease symptoms. While more than 20 therapies are approved for relapsing forms of MS, those with progressive and nonactive disease forms have far fewer options.

Currently, Ocrevus (ocrelizumab) is the only approved treatment for people with PPMS, and mitoxantrone is the only option for those with nonactive SPMS.

KYV-101 is a CAR T-cell therapy aiming to reset a patient’s immune system

KYV-101 belongs to a class of treatments called CAR T-cell therapies, which involve isolating a patient’s immune T-cells and engineering them to carry a man-made receptor — a chimeric antigen receptor or CAR — to target a specific protein. In the case of KYV-101, the receptor targets the CD19 protein, which is found at the surface of immune B-cells that are implicated in MS.

Once modified and expanded in the lab, these cells are infused back to the patient, where they are expected to target and promote the elimination of B-cells. It is believed a single infusion of KYV-101 may provide sustained disease control for people with progressive MS.

Prior to treatment, patients will undergo a preconditioning regimen, called a lymphodepletion regime, to clear out existing T-cells using bendamustine, a chemotherapy.

“We are excited about the interest shown by world-class institutions like Stanford to evaluate the clinical performance of KYV-101 in patients,” said Peter Maag, PhD, CEO of Kyverna. “We look forward to enriching our collective knowledge about the potential paradigm-shifting value of CAR T-cell therapy through these dedicated collaborations between Industry and Academia.”

The Stanford trial will be conducted along with a Kyverna-sponsored Phase 2 clinical trial that was cleared by the U.S. Food and Drug Administration (FDA) earlier this year. The KYSA-7 trial will enroll people with progressive types of MS who failed to respond adequately to other therapies.

The FDA granted fast track status to KYV-101 as a potential treatment for this indication. The designation is intended to accelerate the development of therapies addressing unmet medical needs for people with serious or life-threatening conditions.

The therapy also is being evaluated in other autoimmune disorders: lupus, systemic scleroderma, and myasthenia gravis.

“As CAR T-cell therapies are entering the field of B cell-driven autoimmunity, leveraging on our knowledge and expertise in oncology will provide a faster option to address an unmet medical need and make these potentially life-changing therapies available to non-cancer patients,” said Robert Lowsky, MD, a professor of medicine at Stanford University.