ALLO-605 Granted Fast Track Designation by FDA for Relapsed/Refractory Multiple Myeloma

The FDA granted a fast track designation for ALLO-605 based on its potential to treat patients with relapsed/refractory multiple myeloma who progressed on previous standard multiple myeloma therapies.

ALLO-605 was granted a fast track designation by the FDA for the treatment of patients with relapsed/refractory multiple myeloma due to its potential to address unmet needs for a population of patients whose disease progressed following previous standard therapies.1

Preclinical data assessing ALLO-605 in patients with relapsed/refractory multiple myeloma were presented at the 2020 American Society of Hematology (ASH) Annual Meeting, indicating that the drug demonstrated prolonged persistence and antitumor activity, along with a tolerable safety profile, supporting further clinical investigation.2 The B-cell maturation antigen (BCMA)–targeted CAR T-cell therapy demonstrated an enhanced cytokine secretion, polyfunctionality, and improvements in serial killing activity in an in vitro model. Additionally, in a disseminated mouse model of myeloma, ALLO-605 yielded a 2-fold increase in peak expansion and enhanced survival vs BCMA CAR T cells. This translated to prolonged anti-tumor responses and delays in disease relapse.

However, investigators reported that exposure to target cells was necessary in order to achieve expansion and long-term activity of the BCMA-directed CAR T cells. Investigators did not observe evidence of target- and cytokine-independent proliferation

Additionally, the phase 1 dose escalation portion of the IGNITE trial investigating ALLO-605, Allogene’s first TurboCAR clinical candidate, was initiated in the second quarter of 2021.

“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,” Rafael Amado, MD, executive vice president of research and development and chief medical officer, said in a press release.

ALLO-605, the next-generation of allogeneic CAR T-cell therapy BCMA, is the third prong of Allogene’s approach of targeting BCMA for patients with multiple myeloma. The CAR T product is the first TurboCAR clinical candidate—a next generation platform technology based on programmable cytokine signaling that can work to ultimately to improve the function and potency of allogenic CAR T-cells. ALLO-715 was granted a regenerative medicine advanced therapy (RMAT) designation by the FDA in April 2021. Moreover, data from the phase 1 UNIVERSAL study (NCT04093596), in which patients with relapsed/refractory disease will receive treatment with ALLO-715, read out at the 2020 ASH Annual Meeting. The UNIVERSE trial also began separately enrolling begun enrolling patients in the first half of 2021 in order to evaluate ALLO-715 in combination with an investigational gamma secretase inhibitor, nirogacestat.

Additional findings from the preclinical phase 1 study identified 2 possible strategies to modulate the BCMA CAR T-cell product in order to respond to potential treatment-related toxicities. Investigators accessed the possibility of a CD20-based off switch that could be incorporated into the CAR in order to sensitize cells to rituximab (Rituxan). This resulted in a successful depletion of BCMA CAR T cells. Additionally, investigators were able to confirm the rapid inhibition of BCMA TurboCAR T cells through the use of protein tyrosine kinase inhibitor dasatinib (Sprycel).

“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 said in a press release.

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. Published June 30, 2021. Accessed August 10, 2021. https://tinyurl.com/5d92cpju

2. Cesar Sommer, Regina Lin, Janette Sutton, 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. https://doi.org/10.1182/blood-2020-141477