Allogene Therapeutics, Inc. Reports Positive Results from Phase 1 Universal Study of Single Dose ALLO-715 Allocar T Cell Therapy in Relapsed/Refractory Multiple Myeloma At the 63rd American Society of Hematology Annual Meeting
December 13, 2021 at 11:00 am EST
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Allogene Therapeutics, Inc. positive updated results from the Phase 1 UNIVERSAL study of single dose ALLO-715 in relapsed/refractory (r/r) multiple myeloma. Data were presented in an oral session by Sham Mailankody, MBBS, Assistant Attending Physician at Memorial Sloan Kettering Cancer Center in New York, during the 63rdAmerican Society of Hematology (ASH) Annual Meeting in Atlanta. This study utilizes ALLO-647, Allogene's anti-CD52 monoclonal antibody, as a part of its differentiated lymphodepletion (LD) regimen. As of the October 14, 2021 data cutoff, 48 patients were enrolled with 43 patients evaluable for safety and efficacy. Patients were refractory to their last line of myeloma therapy, had a median of five prior lines of therapy, and 42% were penta-refractory meaning the disease has ultimately become nonresponsive to other approved therapies. Five patients became ineligible for treatment due to rapidly progressing disease. The median time from enrollment to the start of therapy was five days. The Phase 1 UNIVERSAL trial evaluated lymphodepletion followed by ALLO-715 at one of four dose levels (DL1=40M cells, DL2=160M cells, DL3=320M cells, DL4 = 480M cells) and two LD regimens (FCA: fludarabine, cyclophosphamide and ALLO-647 or CA: cyclophosphamide and ALLO-647 only). The updated presentation primarily focuses on the optimized DL3 cell dose and FCA lymphodepletion. The higher CAR T cell doses were associated with an increased response rate and greater AlloCAR T cell expansion. In the DL3 cohort which was selected for cohort expansion, the overall response rate (ORR) increased from 60% reported at ASH 2020 to 71% with 46% of patients achieving a very good partial response (VGPR) or better (VGPR+) up from 40%. VGPR+ is defined as a stringent complete response (sCR), complete response (CR) or VGPR. Of the patients who achieved VGPR+, 92% were Minimal Residual Disease (MRD) negative. As of the data cutoff, the overall median follow-up for efficacy was 3.8 months. The median duration of response is 8.3 months, with nine patients remaining in ongoing response at the time of the data cut-off. The longest ongoing response after cell infusion is 12 months. Results showed that soluble BCMA levels were 10 times lower in responders at Day 28, suggesting soluble BCMA suppression is associated with response. Of the 43 patients evaluable for safety, there was no graft-versus-host-disease (GvHD). Grade 1 and 2 cytokine release syndrome (CRS) was reported in 23 patients (53%) and was manageable with standard therapies. In this heavily pre-treated patient population, infection occurred in 54% of patients, which included three Grade 5 infections, two of which were previously reported. Grade 3+ neutropenia occurred in 70% of patients. Six patients (14%) experienced adverse events of low-grade neurotoxicity, which was reversible. Use of tocilizumab and steroids was infrequent (23% and 14%, respectively). ALLO-715 has been granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA for the treatment of r/r multiple myeloma. As part of the Companys anti-BCMA strategy, the UNIVERSAL trial is also studying consolidated dosing of ALLO-715 using ALLO-647 to selectively extend the window of lymphodepletion. UNIVERSAL is also evaluating ALLO-715 in combination with SpringWorks Therapeutics investigational gamma secretase inhibitor, nirogacestat. The Phase 1 dose escalation portion of the IGNITE trial evaluating ALLO-605, the Companys first TurboCAR candidate, was initiated in Second Quarter 2021. TurboCAR technology allows cytokine activation signaling to be engineered selectively into CAR T cells and has shown the ability to improve the potency and persistence of allogeneic cells in preclinical models. Subject to the clinical hold currently in place, Allogene continues to target 2022 for data from these additional strategies.
Allogene Therapeutics, Inc. is a clinical-stage immuno-oncology company. The Company is focused on development of genetically engineered allogeneic T cell product candidates for the treatment of cancer and autoimmune diseases. It is focused on four core programs: Large B-Cell Lymphoma (LBCL), Chronic Lymphocytic Leukemia (CLL), Autoimmune Disease and Renal Cell Carcinoma. It is developing a pipeline of multiple allogeneic chimeric antigen receptor (CAR) T cell product candidates utilizing protein engineering, gene editing, gene insertion and advanced proprietary T cell manufacturing technologies. Its product candidate, cemacabtagene ansegedleucel, referred to as cema-cel, is an engineered allogeneic CAR T cell product candidate that targets CD19, a protein expressed on the cell surface of B cells and a validated target for B cell driven hematological malignancies. It is focused on developing cema-cel for LBCL and CLL. Its pipeline also includes ALLO-316, ALLO-329 and ALLO-647.
Allogene Therapeutics, Inc. Reports Positive Results from Phase 1 Universal Study of Single Dose ALLO-715 Allocar T™ Cell Therapy in Relapsed/Refractory Multiple Myeloma At the 63rd American Society of Hematology Annual Meeting