Allogene Therapeutics, Inc. Form 8-K Summary
Reporting period/event date: The report covers an event occurring December 9, 2023, involving presentation of Phase 1 ALPHA/ALPHA2 data at the 65th Annual Meeting of the American Society of Hematology. The filing was signed December 19, 2023.
Business Context
Allogene is developing allogeneic, or “off-the-shelf,” CAR T-cell therapies. The filing concerns ALLO-501/501A in relapsed or refractory large B-cell lymphoma (LBCL) and follicular lymphoma (FL), and ALLO-647, an investigational lymphodepleting agent intended to reduce host rejection of allogeneic CAR T cells.
Clinical and Safety Results
- The safety review included 87 Phase 1 patients: 61 with LBCL and 26 with FL.
- Among 33 CAR T-cell-naive patients with relapsed or refractory LBCL treated with ALLO-501/501A manufactured using the Phase 2-selected process, the complete remission rate was 42% and median duration of response was 23.1 months.
- Common adverse events included neutropenia and anemia. The most common Grade 3 or higher events were neutropenia, anemia, and thrombocytopenia.
- Any-grade cytokine release syndrome (CRS) occurred in 24% of patients; one patient experienced Grade 3 CRS.
- Any-grade neurotoxicity occurred in 28%; three percent was Grade 3 or higher.
- No graft-versus-host disease or Grade 3 or higher immune effector cell-associated neurotoxicity syndrome was reported.
- Any-grade infections occurred in 57% of patients and Grade 3 or higher infections in 21%. Cytomegalovirus reactivation occurred in 25% of patients overall and was Grade 3 or higher in 9%.
- Eight patients experienced fatal adverse events that were not related to study treatment.
Material Changes, Outlook, and Regulatory Developments
- The company stated that adding ALLO-647 to standard fludarabine/cyclophosphamide lymphodepletion did not produce adverse events beyond those commonly observed with autologous CAR T-cell therapy.
- Grade 3 or higher cytopenias decreased from Day 28 through Month 4 and were described as consistent with autologous CAR T-cell therapy.
- The EXPAND trial is enrolling in the United States and Europe and is expected to support potential licensure of ALLO-647. Approximately 70 patients with relapsed or refractory LBCL will be randomized to ALLO-647-containing lymphodepletion or fludarabine/cyclophosphamide alone before ALLO-501A infusion. Progression-free survival is the primary endpoint.
- The FDA granted Fast Track Designation for ALLO-647 in adults with relapsed or refractory LBCL.
- Financial results, revenue, profit or loss, cash flow, margins, debt, liquidity, and financing activity are not reported in this filing.
Risks and Contingencies
The programs remain investigational and are subject to clinical, manufacturing, regulatory, and commercial risks. The company cautioned that clinical trials may fail to demonstrate safety or efficacy, the FDA may disagree with its regulatory strategy, and approval may be delayed or denied. The company also cautioned against directly comparing its results with autologous CAR T-cell data because of differences in trial design, patient populations, follow-up, and products.
Key Facts for Investor Verification
- Verify the complete remission and duration-of-response results, including follow-up duration and the applicable patient subgroup.
- Review the full safety dataset, including the causes and attribution of the eight fatal adverse events.
- Monitor EXPAND enrollment, randomization, progression-free survival results, and any changes to the trial design.
- Confirm the scope and implications of the FDA Fast Track Designation; it does not constitute marketing approval.
- Review the company’s September 30, 2023 Form 10-Q for cash runway, liquidity, operating losses, commitments, and risk factors, which are not included in this 8-K.