Updated data from 3 of the company’s programs were presented at an R&D showcase.
Allogene Therapeutics has presented data from chimeric antigen receptor (CAR) T-cell therapies in its ALPHA studies (NCT03939026; NCT04416984) in large B-cell lymphoma (LBCL), its UNIVERSAL study (NCT04093596) in multiple myeloma, and its TRAVERSE study (NCT04696731) in clear cell renal cell carcinoma (RCC).
"From the very beginning, one of the biggest questions facing the field of allogeneic CAR T has been whether an off-the-shelf product can match the high durability bar set by autologous therapies. We believe the longer-term follow up data from our Phase 1 studies establish that this is indeed possible," David Chang, MD, PhD, president, chief executive officer and cofounder,Allogene, said in a statement. "As we look to confirm our exciting results in the first allogeneic CAR T Phase 2 trial for which we are enrolling, I believe we are entering a new phase of development for AlloCAR T, one in which the field can turn its attention to “when” and not “if” these product candidates will begin to provide great benefit to patients with cancer.”
The ALPHA studies of ALLO-501 and ALLO501A (the latter manufactured with a new process to be carried forth in the newly initiated phase 2 trial) revealed that as of October 25, 2022, all 9 patients treated with CAR T products manufactured with the company’s Alloy process achieved a complete response (CR) at 6 months with 8 CRs ongoing after over 26 months. Patients treated with a single-dose regimen, as opposed to the earlier method of 2 split infusions (n = 12), had an overall response rate (ORR) of 67% with 58% achieving CRs.
Half (n = 4) the patients that had follow-up of over 6 months had CRs at both 6 and 12 months. There were no dose limiting toxicities (DLTs) or cases of graft-vs-host disease (GvHD). One patient (8%) experienced a serious (over grade 3) infection adverse event (AE) and 2 (17%) experienced prolonged serious cytopenia. There was a previously reported grade 5 AE.
The UNIVERSAL study of ALLO-715 with FCA39 or FCA60 lymphodepletion yielded a 67% ORR in patients with LCA60 lymphodepletion at a median follow-up of 14.8 months as of October 11, 2022. Very good partial response (VGPR) rate was 42% and all patients that achieved VGPR had minimal residual disease negativity. Median duration of response was 9.2 months, with the longest ongoing response at 24 months. Eight patients (29%) had serious AEs of infection and prolonged cytopenia. One previously-reported grade 5 AE occurred.Allogene is planning a pivotal phase 2 trial of ALLO-715.
The most recent data reported, as of November 17, 2022, were from the TRAVERSE study. Investigators found that 9 patients with RCC treated with ALLO-316 had a disease control rate of 100% with 3 partial responses (longest response of 8 months). CD70 expression-dependent tumor shrinkage was observed. This CAR T also had a manageable safety profile with no GvHD and 1 DLT of liver enzyme elevations in the second dose level. Three patients had serious cytopenia, there was 1 case of grade 3 cytokine release syndrome, and low-grade neurotoxicity in 3 patients.
Allogene also noted that both liquid tumor programs demonstrated manufacturing feasibility, with 92% of all enrolled patients in both programshaving received the cells with 100% of infused product manufactured and released as per product specifications.
“We have undertaken a rigorous step-by-step process to evaluate, understand and optimize our AlloCAR T platform. Our continuous learning approach has enabled an industry-leading pipeline of off-the-shelf AlloCAR T product candidates for hematologic and solid tumor malignancies, and we are delighted to be sharing some initial, highly promising data in solid tumors,” Rafael Amado MD, Executive Vice President of Research and Development, Allogene, added to the statement. “Our focus is to advance this pipeline, including the execution of our Phase 2 trial for ALLO-501A and preparation for a potential Phase 2 trial on ALLO-715. We believe success in this endeavor will enable us to bring the promise of cell therapy to far more patients in need.”