New gene therapy for multiple myeloma enters clinical trial

inMMyCAR is evaluating safety and effects of KLN-1010 in up to 40 adults

Steve Bryson, PhD avatar

by Steve Bryson, PhD |

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The first patient has been dosed in a Phase 1 clinical trial that’s testing a gene therapy for people with recurring or treatment-resistant multiple myeloma.

The study, dubbed inMMyCAR (NCT07075185), is evaluating the safety, pharmacological properties, and preliminary efficacy of Kelonia Therapeutics’ KLN-1010 at sites in Australia in up to 40 adults. KLN-1010 is designed to generate cancer-fighting CAR-T cells inside the body after a single treatment, eliminating the need for cell harvesting, pre-treatment chemotherapy, or cell manufacturing associated with current CAR-T cell therapies.

“KLN-1010 offers hope to multiple myeloma patients who can’t access today’s CAR-T cell therapies,” Kevin Friedman, PhD, CEO and founder of Kelonia, said in a company press release. “This first-in-human dosing marks a major milestone toward a future where CAR-T benefits can be delivered without preparative chemotherapy or bespoke manufacturing delays, and at virtually any hospital around the world.”

Myeloma is a rare blood cancer that affects plasma cells, immune cells that produce antibodies to help fight infections. While current treatments can drive the cancer to remission, many patients don’t respond, or are refractory. And it will often recur, or relapse, after a few months or years in those who do respond.

“Multiple myeloma can be a challenging disease to treat as most patients experience relapse after initial treatment, and many become resistant to currently available therapies,” said Simon Harrison, PhD, director of the Centre of Excellence in cellular immunotherapy at the Peter MacCallum Cancer Centre, in Australia, and inMMyCAR’s lead investigator.

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A different kind of CAR-T cell therapy

In standard CAR-T cell therapy, a patient’s immune T-cells are harvested and genetically modified to produce a chimeric antigen receptor (CAR), which enables them to target and destroy cancer cells more precisely. Before receiving the modified cells, patients undergo a conditioning regimen called lymphodepletion, which uses chemotherapy agents to wipe out existing immune cells and make room for the new CAR-T cells.

KLN‑1010 is designed to generate CAR-T cells in the body that target BCMA, a protein on multiple myeloma cells. Unlike traditional CAR‑T therapies, it’s administered via direct transfusion into the bloodstream to eliminate limitations faced by current CAR-T approaches, including limited access to treatment, long wait times, and preconditioning chemotherapy.

In vivo CAR-T cell therapies would be transformative for these patients, providing rapid access to potentially life-saving treatments,” Harrison said. “We’re at a pivotal moment, in which we’re taking important steps to make such therapies a reality in Australia through highly novel clinical trials, and I’m proud to play a role in ushering in these innovative therapies.”

A multicenter Phase 1, dose-escalation clinical trial, inMMyCAR will assess the safety and preliminary efficacy of a single dose of KLN-1010 in adults with relapsed and refractory multiple myeloma. The participants must have received at least three prior lines of therapy, including an immunomodulator, a proteasome inhibitor, and a CD38 inhibitor.

The study will also assess the number of CAR-T cells in the blood and the amount of CAR-T cell DNA in blood and bone marrow up to two years after treatment. Preliminary efficacy will be evaluated according to the International Myeloma Working Group (IMWG) response criteria, from dosing until disease progression or up to 15 years, whichever comes first. The first patient was dosed at Royal Prince Alfred Hospital in Australia by Professor Joy Ho, PhD, an inMMyCAR investigator.

“Dosing the first patient in the inMMyCAR Phase 1 study is a tremendous milestone and marks significant advancement toward bringing KLN-1010 to patients who need it most,” Ho said. “KLN-1010 has the potential to deliver the full promise of CAR-T cell therapies without the complex manufacturing requirements, lengthy production timelines, and toxic lymphodepleting chemotherapy that ex vivo CAR-T cell therapies require. We believe it has the potential to revolutionize CAR-T therapy in myeloma.”