|The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Two allogeneic chimeric antigen receptor (CAR) T-cell (CAR-T) therapy products — ALLO-501 and ALLO-647 — appear to be safe for patients with relapsed or refractory large B-cell lymphoma or follicular lymphoma (LBCL/FL), according to first-in-human data from the ALPHA study.
ALLO-501 is a genetically modified anti-CD19 CAR-T in which the TCR alpha constant gene is disrupted to reduce the risk of graft-vs-host disease and the CD52 gene is disrupted to permit the use of ALLO-647, an anti-CD52 monoclonal antibody, for selective and prolonged host lymphodepletion.
“Allogeneic CAR-T therapy may provide the benefits of autologous CAR-T cell therapy while also addressing its challenges,” said Sattva Swarup Neelapu, MD, of the University of Texas MD Anderson Cancer Center in Houston, who presented the results as part of the ASCO20 Virtual Scientific Program. “It has the potential to treat all eligible patients, the convenience of repeat dosing, and simplifies the logistics of manufacturing.”
The phase 1 study included 22 patients with relapsed or refractory LBCL/FL who had received at least 2 prior lines of therapy. Patients received fludarabine, cyclophosphamide, and ALLO-647 39 mg or 90 mg followed by ALLO-501 at 1 of 3 dose levels (40 x 106, 120 x 106, and 360 x 106).
At data cutoff, 22 patients were evaluable for safety and 19 for efficacy. A single patient discontinued the trial due to kidney injury prior to lymphodepletion. The median number of prior lines of therapy was 4.
Of the 19 individuals for whom efficacy could be evaluated, 3 patients experienced disease progression — and all 3 of these individuals had received prior CAR-T therapy with an autologous CAR-T.
The median time from enrollment to start of lymphodepletion was 5 days, reflecting the potential advantage of allogenic CAR-T therapy, Dr Neelapu said.
No dose-limiting toxicities or GVHD has occurred to date.
About one-third (32%) of patients developed cytokine release syndrome (CRS), but only one patient had grade 3 CRS. All were reversible. About half of patients had infusion reactions to ALLO-647 and another half had infections.
The best overall response rate among patients was 63% and the best complete response rate was 37%. The complete response rate seemed to be higher at the higher ALLO-647 dose.
Most patients achieved tumor shrinkage, Dr Neelapu said. Nine of 12 who responded to treatment are continuing to show a response.
He also noted that 1 patient who progressed after a partial response was re-dosed with ALLO-501 at 120 x 106 and the higher dose of ALLO-647 and achieved a complete remission, but this patient was not considered for the efficacy analysis.
“Overall these results suggest that the safety and short-term efficacy in terms of response rate for this product is comparable to autologous CAR-T products that are in clinic,” Dr Neelapu said.
Disclosure: Some of the authors disclosed financial relationships with pharmaceutical and/or medical companies. For a full list of disclosures, please refer to the original abstract.
Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2020 meeting by visiting the conference page.
Neelapu SS, Munoz J, Locke FL, et al. First-in-human data of ALLO-501 and ALLO-647 in relapsed/refractory large B-cell or follicular lymphoma (R/R LBCL/FL): ALPHA study. Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr 8002.