Arcellx, Inc. has received notification from the U.S. Food and Drug Administration (FDA) that a clinical hold has been placed on its CART-ddBCMA investigational new drug (IND) for the treatment of patients with relapsed or refractory multiple myeloma (rrMM).
The clinical hold was received on June 16, following a recent patient death. The company said it believes limitations on bridging therapy are a contributing factor and is working with the FDA to amend the protocol to expand options for patients that are consistent with current clinical practice. The FDA has provided clearance to Arcellx to continue to dose patients who have undergone lymphodepletion.
“The safety and well-being of patients enrolled in our studies is our top priority,” said Rami Elghandour, Arcellx’s chairman and chief executive officer.
“In coordination with our investigators, data safety monitoring board (DSMB), and our partners at Kite Pharma, we are working with FDA to address the clinical hold. The expansion of bridging therapy regimens is consistent with what’s currently available in clinical practice and is in the best interest of patients. Additionally, we continue to evaluate other potential improvements to the study.
“We remain confident that CART-ddBCMA is a potential best-in-class therapy for the treatment of patients with rrMM based on the clinical profile observed in the patients dosed to date across our studies. The drug product release characteristics from iMMagine-1 are consistent with those from our phase 1 study. The manufacturing success rate remains 100% while ramping Lonza, our cell therapy manufacturer, to full scale. Fourteen clinical sites have been opened and study enrollment is tracking to our expectations. We look forward to resolving this matter expeditiously and to continue to advance our therapy to the benefit of patients suffering from rrMM.”
About iMMagine-1
iMMagine-1 is a phase 2 pivotal, open-label, multicenter clinical trial designed to evaluate CART-ddBCMA, a BCMA-specific CAR-modified T-cell therapy utilizing Arcellx’s novel BCMA-targeted binding domain, for the treatment of adult patients with relapsed or refractory multiple myeloma.
The primary objective of this study is to evaluate the overall response rate over a 24-month period. In addition to safety, secondary endpoints include depth of disease response, duration of response, and overall survival over a 24-month period.
Multiple myeloma
Multiple myeloma is a type of hematological cancer in which diseased plasma cells proliferate and accumulate in the bone marrow, crowding out healthy blood cells and causing bone lesions, loss of bone density, and bone fractures. These abnormal plasma cells also produce excessive quantities of an abnormal immunoglobulin fragment, called a myeloma protein (M protein), causing kidney damage and impairing the patient’s immune function.
Multiple myeloma is the third most common hematological malignancy in the U.S. and Europe, representing approximately 10% of all hematological cancer cases and 20% of deaths due to hematological malignancies. The median age of patients at diagnosis is 69 years with one-third of patients diagnosed at an age of at least 75 years. Because it tends to afflict patients at an advanced stage of life, patients often have multiple co-morbidities and toxicities that can quickly escalate and become life-endangering.
About Arcellx’s CART-ddBCMA
CART-ddBCMA is Arcellx’s BCMA-specific CAR-modified T-cell therapy utilizing the company’s novel BCMA-targeting binding domain for the treatment of patients with relapsed or refractory multiple myeloma. CART-ddBCMA is currently in a phase 2 study.
Arcellx’s proprietary binding domains are novel synthetic proteins designed to bind specific therapeutic targets. CART-ddBCMA has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the FDA.