Kelonia's in vivo CAR-T data will feature at ASH

Kelonia Therapeutics only started human testing of its in vivo CAR-T therapy for multiple myeloma in August, but already has data to warrant grabbing a headline slot at the upcoming ASH haematology congress.

The first readout from its inMMyCAR study – albeit only in three patients – shows that all of them have achieved minimal residual disease (MRD) negativity at four weeks that persisted for three months in one patient with the longest follow-up – effectively a 100% partial response rate.

The study, which will eventually recruit around 40 subjects, is testing one-shot treatment with BCMA-targeted KLN-1010 – at escalating doses – in patients with relapsed and refractory multiple myeloma who have been previously treated with at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug (IMiD), and a CD38-directed monoclonal antibody, i.e. Johnson & Johnson/Genmab's Darzalex (daratumumab) or Sanofi's Sarclisa (isatuximab).

While still very early, the initial readout from inMMyCAR can be viewed as a key milestone in the development of therapies that allow patients to make CAR-Ts in their own bodies, warranting its place in the late-breaker sessions at ASH, which gets underway on 6th December in Orlando, Florida.

These in vivo CAR-Ts don't require the costly and sometimes lengthy process of harvesting, modifying, and cultivating patients' own cells needed for ex vivo CAR-Ts, as well as the need for patients to undergo aggressive lymphodepletion therapy to destroy their bone marrow before treatment.

The result is also remarkable as it involves patients receiving the lower doses of KLN-1010, and, seemingly at least, before any dose-limiting toxicities have been identified.

Two of the patients experienced grade 2 cytokine release syndrome (CRS), a recognised side effect with current ex vivo CAR-Ts that clinicians are now well experienced at managing, and no cases of neurotoxicity, which has also plagued first-generation CAR-Ts.

Recognising that experience, the FDA relaxed patient monitoring requirements and other restrictions designed to minimise these side effects earlier this year.

"In these early patients, we are seeing both rapid MRD-negative responses and persistent memory-phenotype CAR-T cells, a combination that has been strongly prognostic for durable clinical benefit with existing CAR-T approaches,” said Simon Harrison, director of the Centre of Excellence in Cellular Immunotherapy at the Peter MacCallum Cancer Centre in Australia, and the lead author of the late-breaking abstract.

"Achieving these outcomes without lymphodepleting chemotherapy or CAR-T cell manufacturing underscores the potential of this in vivo approach to fundamentally expand access to CAR-T therapy for patients with relapsed and refractory multiple myeloma," he added.

Kelonia's in vivo CAR-T platform has attracted partnerships with Astellas and Johnson & Johnson.