Next-Generation CAR T-Cell Therapy, ALLO-605, Granted Fast Track Designation

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The FDA’s designation follows positive data presented at the 2020 ASH meeting.

The FDA has granted fast track designation to Allogene Therapeutics’ ALLO-605 for the treatment of relapsed/refractory multiple myeloma, a CAR T-cell therapy that uses the company’s proprietary TurboCAR Technology.1

The agent is being evaluated in the phase 1 IGNITE dose escalation trial that initiated in the second quarter of 2021. It is the company’s first candidate to be made with their TurboCAR technology, which is designed to improve the function and potency of their AlloCAR T cells. Allogene believes that these properties may also enable the therapy to be efficacious in solid tumors and increase efficacy in hematologic malignancies.

“We are very pleased with the continued momentum of our anti-B cell maturation antigen (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, Allogene Therapeutics, in a statement.

ALLO-605 incorporates ALLO-647, an Allogene monoclonal antibody (mAb) with the TurboCAR technology to allow for cytokine activation signaling to be engineered selectively into CAR T cells. The agent and accompanying study makes up the third prong of the company’s aim to target BCMA for the treatment of multiple myeloma.

WATCH NOW: CAR T-Cell Therapy's Future in Multiple Myeloma: Mounzer Agha, MD

“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,” Amado added.

Preclinical results from the ALLO-605 study were previously presented at the 63rd Annual meeting of the American Society of Hematology (ASH), December 5-8, 2020. Investigators showed that in vitro, BCMA TurboCAR T cells showed enhanced cytokine secretion, polyfunctionality, and improved serial killing activity. In a disseminated mouse model of multiple myeloma, BCMA TurboCAR T cells exhibited at least a 2-fold increase in peak expansion and enhanced survival and persistence compared to BCMA CAR T cells, resulting in prolonged antitumor responses and delaying relapse, while exposure to target cells was required for long-term activity.2

In April 2021, the FDA granted regenerative medicine advanced therapy (RMAT) designation to ALLO-715, another CAR T-cell therapy by Allogene.3 ALLO-715 is aimed to target an unmet need for patients wwith refractory multiple myeloma. It features a human-derived single-chain variable fragment anti-BCMA cell with a 4-1BB costimulatory domain.

“RMAT designation was granted based on our encouraging initial clinical experience in heavily pretreated patients. ALLO-715 demonstrated for the first time that an allogeneic CAR T therapy directed at BCMA can achieve deep clinical responses while eliminating the need for bridging therapy and delays associated with autologous CAR T manufacturing,” said Amado said in a previous statement. “We look forward to completing the UNIVERSAL study and working closely with the FDA as we seek to rapidly advance this important therapeutic alternative to patients with advanced multiple myeloma.”

The UNIVERSAL study (NCT04093596) evaluating ALLO-715 began enrolling patients in the first half of 2021 to evaluate ALLO-715 in combination with the investigational gamma secretase inhibitor, nirogacestat.1 Data presented at ASH from the study showed that at the 320 x 106 CAR cells dose plus the ALLO-647 lymphodepletion regimen, the therapy elicited a 60% overall response rate (ORR; n = 6/10), which included a very good partial-plus response (VGPR+) in 4 patients (40%).4

REFERENCES
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 Therapeutics. June 30, 2021. https://www.biospace.com/article/releases/allogene-therapeutics-granted-fda-fast-track-designation-for-allo-605-the-first-turbocar-t-cell-therapy-for-the-treatment-of-relapsed-refractory-multiple-myeloma/
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 (Supplement 1): 8. doi:10.1182/blood-2020-141477
3. Allogene Therapeutics announces FDA regenerative medicine advanced therapy (RMAT) designation granted to ALLO-715, an AlloCAR T™ cell therapy in development for relapsed/refractory multiple myeloma. News release. Allogene Therapeutics. April 21, 2021. Accessed April 21, 2021. https://bit.ly/3atevaM
4. Mailankody S, Matous JV, Liedtke M, et al. Universal: an allogeneic first-in-human study of the anti-BCMA ALLO-715 and the anti-CD52 ALLO-647 in relapsed/refractory multiple myeloma. Presented at: 2020 ASH Annual Meeting and Exposition; December 5-8, 2020; virtual. Abstract 129.
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