▎WuXiEdited by Kant Content Team

Today, Kite Pharma, a subsidiary of Gilead Sciences, and Arcellx announced that they will present the latest clinical trial results of their jointly developed BCMA-targeted CAR-T cell therapy, anitocabtagene autoleucel (anito-cel), for the treatment of patients with relapsed or refractory multiple myeloma (RRMM) at this year’s American Society of Hematology (ASH) Annual Meeting. The abstract results released so far indicate,The overall response rate (ORR) for patients treated with anito-cel reached 100%, with a complete response/stringent complete response (CR/sCR) rate of nearly 80%. Additionally, no cases of certain late-onset neurotoxicity were observed in the patients.The related Phase 3 clinical study, iMMagine-3, was initiated in the second half of 2024, and the first patient has been dosed.

Multiple myeloma is a blood cancer where plasma cells proliferate and accumulate in the bone marrow, crowding out healthy blood cells, leading to bone damage, decreased bone density, and fractures.These abnormal plasma cells also produce large amounts of abnormal immunoglobulin fragments, known as myeloma proteins (M-proteins), causing kidney damage and weakening the patient's immune function.Multiple myeloma is the third most common hematologic malignancy in Europe and the United States, accounting for approximately 10% of all blood cancer cases and 20% of deaths from hematologic malignancies.The median age at diagnosis for patients was 69 years, with one-third of the patients aged 75 years or older.Since multiple myeloma tends to affect older patients, who often have multiple comorbidities, the condition can rapidly deteriorate and become life-threatening.

At this year's ASH conference, the two companies will present the latest progress from the Phase 1 clinical study of anito-cel for the treatment of patients with RRMM. The study enrolled a total of 40 patients, 38 of whom received anito-cel treatment. According to the evaluation based on the International Myeloma Working Group (IMWG) criteria,All patients achieved a clinical response, with an overall response rate of 100%, a CR/sCR rate of 79% (30/38), five patients reached a very good partial response (≥VGPR rate of 92%), and three patients achieved a partial response.Among patients eligible for minimal residual disease (MRD) testing (n=28), 25 patients (89%) achieved 10.^-5Horizontal MRD negativity. At a median follow-up time of 38.1 months, the median overall survival had not yet been reached, and the median progression-free survival was 30.2 months. The safety profile was manageable, with no delayed neurotoxicity observed to date, including Parkinson's symptoms, cranial nerve palsy, and Guillain-Barré syndrome.

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At this year's ASH conference, the two companies will also present preliminary results from the Phase 2 registrational study iMMagine-1 of anito-cel for the treatment of RRMM patients. As of June 1, 2024, a total of 58 patients had received anito-cel infusion and completed at least two months of follow-up post-infusion. These patients had previously undergone a median of at least four lines (range: 3-8) of therapy.

Analysis showed that, at a median follow-up time of 10.3 months (range: 2.0-17.8), based on the IMWG criteria as assessed by the investigators,The overall response rate (ORR) was 95% (55/58), and the CR/sCR rate was 62% (36/58).Among patients evaluable for MRD testing (n=39), 36 patients (92%) achieved at least 10^-5Horizontal MRD negativity.The 6-month progression-free survival (PFS) and overall survival rates estimated by Kaplan–Meier were 90% (95% CI: 77-96) and 95% (95% CI: 85-98), respectively.The median progression-free survival and median overall survival of the patients have not been reached yet. The therapy has also demonstrated manageable safety, with no delayed neurotoxicity observed to date, including Parkinson's symptoms, cranial nerve palsy, and Guillain-Barré syndrome.

Anito-cel (formerly known as ddBCMA) is a BCMA-targeted CAR-T cell therapy developed using Arcellx's innovative compact binding domain, D-Domain.The therapy has received Fast Track designation, Orphan Drug designation, and Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. FDA. Arcellx has entered into a global strategic collaboration and licensing agreement with Kite Pharma to jointly develop and commercialize anito-cel for the treatment of patients with RRMM. Currently, anito-cel is being studied in clinical trials for patients with 4th-line and above RRMM (iMMagine-1) as well as for patients in earlier treatment lines (iMMagine-3).

The recently initiated iMMagine-3 trial is a global Phase 3 randomized controlled study designed to compare the efficacy and safety of anito-cel versus standard therapy in RRMM patients who have previously received 1 to 3 prior lines of treatment, including immunomodulatory agents and anti-CD38 monoclonal antibodies. The trial aims to enroll approximately 450 adult patients. Conducted across approximately 130 research centers in North America, Europe, and other regions, the study was launched and dosed its first patient in the second half of 2024.

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References:

[1] Arcellx to Present Clinical Data for Its Phase 1 and iMMagine-1 Studies in Patients with Relapsed or Refractory Multiple Myeloma at the 66th ASH Annual Meeting and Exposition and Announces Progress in iMMagine-3 Study. Retrieved November 5, 2024 from https://ir.arcellx.com/news/news-details/2024/Arcellx-to-Present-Clinical-Data-for-Its-Phase-1-and-iMMagine-1-Studies-in-Patients-with-Relapsed-or-Refractory-Multiple-Myeloma-at-the-66th-ASH-Annual-Meeting-and-Exposition-and-Announces-Progress-in-iMMagine-3-Study/default.aspx

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