Fast Track Designation Granted to Multiple Myeloma CAR T Therapy ALLO-605

The FDA has granted a fast track designation to ALLO-605, a next-generation allogeneic CAR T-cell therapy for the treatment of relapsed or refractory multiple myeloma.

The FDA has granted a fast track designation to ALLO-605, a next-generation allogeneic CAR T-cell therapy for the treatment of relapsed or refractory multiple myeloma, according to a press release by Allogene Therapeutics.1

ALLO-605 targets the B-cell maturation antigen and has the potential to fill an unmet clinical need for patients who have failed other standard multiple myeloma therapies. The agent utilizes TurboCAR technology, which allows for cytokine activation signaling which is selectively engineered into CAR T cells. A phase 1 study dose-escalation study, IGNITE, is currently underway.

“We are very pleased with the continued momentum of our anti-BCMA portfolio for patients with multiple myeloma and look forward to making allogeneic CAR T therapy a potential option for these patients,” said Rafael Amado, MD, executive vice president of research and development and chief medical officer of Allogene Therapeutics, in a press release. “With studies now underway for ALLO-715 alone and in combination with a gamma-secretase inhibitor, as well as ALLO-605 as our next-generation CAR T, we are taking an aggressive three-pronged approach aimed at exploring the unique attributes of AlloCAR T therapies for patients with rapidly progressing disease.”

Preclinical models found that ALLO-605 induced prolonged antitumor responses and persistence as well as a favorable safety profile. These results support the clinical investigation of the agent, according to research presented at 2020 American Society of Hematology’s Annual Meeting.2

The company’s other multiple myeloma CAR T-cell product, ALLO-715, was granted a regenerative medicine advanced therapy designation (RMAT designation) in April 2021. The off-the-shelf product proved to be safe and effective in a heavily pretreated population.

The RMAT designation was granted based on results of the phase 1 Universal study (NCT04093596), which had an estimated enrollment of 132 participants and an estimated completion date of November 2024. Primary end points include rate of dose-limiting toxicities and overall safety and tolerability. Secondary end points include cellular kinetics of ALLO-715, antitumor activity of ALLO-715, pharmacokinetics of ALLO-647, and antitumor activity of ALLO-715 and ALLO-647.

During the study, patients received either ALLO-647, ALLO-715, or nirogacestat. ALLO-715 was given at 4 different dose levels, 40 x 106, 160 x 106, 320 x 106, and 480 x 106.

In order to participate, patients must have a diagnosis of relapsed/refractory multiple myeloma with measurable disease, have received at least 3 prior lines of therapy, an ECOG performance status of 0 or 1, and adequate hematologic, renal, hepatic, pulmonary, and cardiac functions. Patients with a history of central nervous system involvement, a history of thyroid disorder, or a history of HIV infection are not eligible to participate.3

The median prior lines of therapy were 5, ranging from 3 to 11, with 31.6% of patients experiencing stage 3 disease. Over half of patients, 52.6%, had high-risk cytogenetics.

ALLO-715 had a response rate of 60%, with 80% of those responses being durable. Common AEs included anemia (41.2%), neutropenia (41.2%), and lymphopenia (29.4%). 

1.Allogene Therapeutics granted FDA fast track designation for ALLO-605, the first TurboCAR™ T cell therapy, for the treatment of relapsed/refractory multiple myeloma. News release. Allogene Theraputics. June 30, 2021. Accessed August 12, 2021.
2. Sommer C, Lin R, Sutton J, et al. Preclinical Evaluation of ALLO-605, an Allogeneic BCMA Turbocar TTM Cell Therapy for the Treatment of Multiple Myeloma. Blood 2020;136(1): 8. doi:
3. Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL) (UNIVERSAL). Accessed August 12, 2021.