HaemaLogiX and Peter MacCallum Cancer Centre to Collaborate on Kappa-Type Multiple Myeloma CAR-T Trial

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KMA.CAR-T is directed at Kappa Myeloma Antigen, a receptor exclusively appearing on myeloma cells in kappa-type MM.

HaemaLogiX and Peter MacCallum Cancer Centre have formed an agreement to collaboratively advance KMA.CAR-T, an investigational chimeric antigen receptor T-cell (CAR-T) therapy intended to treat kappa-type multiple myeloma (MM), into a phase 1 clinical trial.

HaemaLogiX and Peter MacCallum Cancer Centre have thus far collaborated on the development and preclinical evaluation of KMA.CAR-T. KMA.CAR-T is directed at Kappa Myeloma Antigen (KMA), a receptor appearing on myeloma cells in kappa-type MM. KMA is also expressed on occasional mononuclear cells in healthy tonsillar and mucosal secondary lymphoid tissue, but not on peripheral blood B-cells, healthy plasma cells, or hematopoietic stem cells.1,2 As such, the CAR-T is not expected to destroy healthy immune cells. Notably, in patients with relapsed/refractory MM, KMA is expressed at greater cell density on malignant plasma cells than B-cell maturation antigen, the target of idecabtagene vicleucel and ciltacabtagene ciloleucel, the 2 FDA-approved CAR-T therapies for MM.

“CAR-T cell therapy is now a realistic option for myeloma patients who have failed standard of care treatments,” Rosanne Dunn, PhD, the director, chief scientific officer, and founder of HaemaLogiX said in a statement.1 “We’re excited to progress KMA.CAR-T to the clinic in collaboration with Peter Mac, a renowned Australian cancer hospital and research institute that has been involved in the development of many of the CAR-T therapies now approved as treatments.”

HaemaLogiX and Peter MacCallum Cancer Centre, which plan to work together on developing the manufacturing process and carrying out the first-in-human study, anticipate an initial enrollment of 6 patients in the trial.1 A later potential expansion to 12 participants is planned.

“CAR-T cell therapy is a game-changer in the treatment of certain blood cancers, such as multiple myeloma,” Simon Harrison, PhD, MBBS, MRCP, FRCPath, FRACP, the director of the Peter Mac Centre of Excellence in Cellular Immunotherapy, added to the statement.1 “We are delighted to continue our project with HaemaLogiX to translate the preclinical potential of KMA.CAR-T into a novel first-in-human clinical trial therapy.”

Earlier this year, Dunn presented preclinical proof-of-concept (POC) data from the research collaboration with Peter MacCallum Cancer Centre in a poster at the American Association for Cancer Research (AACR) Annual Meeting 2023, held April 14-19, 2023, in Orlando, Florida.2 The poster covered evaluations of transduction efficiency and expansion for antiKMA CAR T-cells derived from human peripheral blood mononuclear cells supplied by healthy donors, with high CAR expression and “healthy expansion” reported. Furthermore, in in vitro assays, the antiKMA CAR T-cells demonstrated the ability to recognize and destroy KMA-expressing MM cells. Antitumor activity was also observed in a xenograft mouse model treated with antiKMA CAR T-cells.

“We successfully generated human antiKMA CAR T-cells with high and stable CAR expression and a predominately memory T cell phenotype,” first author Jessica Li, PhD, a development scientist in the Centre of Excellence in Cellular Immunotherapy at the Peter MacCallum Cancer Centre and colleagues summarized.2 “The CAR-T cells selectively killed KMA-expressing tumor lines, secreted interferon-gamma upon target recognition, and demonstrated potent antitumor activity in a xenograft model. AntiKMA CAR-T cell therapy therefore represents a novel and potent treatment, ready to enter a phase 1 clinical trial for patients with myeloma.”

REFERENCES
1. Haemalogix to take KMA.CAR-T to ph1 trial with Peter Mac. News release. HaemaLogiX Ltd. July 25, 2023. Accessed August 8, 2023. https://www.haemalogix.com/news/HaemaLogiX-to-take-KMA.CAR-T-to-Ph1-trial-with-Peter-Mac
2. Li J, Haynes NM, Cummins KD, et al. Cellular immunotherapy targeting kappa myeloma antigen for the treatment of multiple myeloma. Presented at: AACR Annual Meeting. April 14-19, 2023; Orlando, FL. Abstract 4074.

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