Business Context and Reporting Period
Allogene Therapeutics, Inc. filed this Form 8-K on May 19, 2021 to report clinical results for its allogeneic CAR T-cell programs, developed with Servier. The filing covers interim data through April 19, 2021, with certain follow-up information through May 12, 2021. Programs discussed include ALLO-501 and ALLO-501A in relapsed/refractory non-Hodgkin lymphoma (NHL), and ALLO-647 lymphodepletion data from NHL and multiple myeloma studies.
Key Clinical and Operating Metrics
- ALPHA trial—ALLO-501: 42 patients enrolled and 41 treated. Among 32 CAR T-naive evaluable patients, overall response rate was 75% and complete response rate was 50%; response rate was 64% in large B-cell lymphoma and 81% in follicular lymphoma.
- Durability: 29% of CAR T-naive patients remained in complete response six months after a single infusion. As of May 12, 2021, three large B-cell lymphoma patients and eight follicular lymphoma patients remained in complete response, with the longest ongoing responses at 15 months.
- ALPHA safety: Cytokine release syndrome occurred in 27% of patients and was limited to Grade 1 or 2. One patient experienced Grade 3 immune effector cell-associated neurotoxicity syndrome. No dose-limiting toxicities or graft-versus-host disease were observed. Infections occurred in 61% of patients, including Grade 3 or higher infections in 24%.
- ALPHA treatment-emergent deaths: Five deaths occurred without disease progression: one each from fungal pneumonia, arrhythmia, and stroke, and two from community-acquired COVID-19. Three of these patients were in ongoing complete response at death.
- ALPHA2 trial—ALLO-501A: 13 patients enrolled and 12 treated. Among nine evaluable patients treated at the targeted 120 million CAR-positive cell dose, overall response rate and complete response rate were each 56%. All complete responses remained ongoing as of May 12, 2021, with median follow-up of 2.3 months.
- Consolidation dosing: Across eight patients treated in consolidation cohorts in the ALPHA studies, overall response rate was 75% and complete response rate was 63%; four patients converted from partial response at Day 28 to complete response at Day 56.
- ALPHA2 safety: No dose-limiting toxicities, graft-versus-host disease, or immune effector cell-associated neurotoxicity syndrome were observed. Across all 13 patients, cytokine release syndrome occurred in 15% and infections in 54%.
- ALLO-647: In combination with fludarabine and cyclophosphamide, ALLO-647 produced exposure-dependent lymphodepletion. The company reported correlations between ALLO-647 exposure, lymphocyte depletion, CAR T-cell expansion, and clinical response.
- Financial metrics: The filing does not provide revenue, profit or loss, cash flow, margins, debt, liquidity, or other financial statement metrics.
Material Changes Versus Prior Comparable Period
This Form 8-K is primarily a clinical-trial update and does not present a prior-period financial comparison. The principal developments are interim efficacy and safety data for ALLO-501A, additional consolidation-dose results, and consolidated ALLO-647 safety and pharmacokinetic/pharmacodynamic analyses.
Guidance, Outlook, Risks, and Unusual Items
- The company plans to collect additional consolidation-arm data, finalize the ALLO-501A dose and lymphodepletion schedule, and discuss the Phase 2 design with regulators.
- Subject to additional data and regulatory feedback, management planned to begin the Phase 2 portion of ALPHA2 by the end of 2021.
- The UNIVERSAL multiple myeloma study included two Grade 5 events. One was attributed to progressive myeloma and lymphodepletion; the other involved adenovirus reactivation in a heavily pretreated patient with pre-existing lymphopenia.
- ALLO-715 received FDA Regenerative Medicine Advanced Therapy designation for relapsed/refractory multiple myeloma. The designation does not constitute approval or establish efficacy.
- The results are interim and based on small patient populations. Outcomes may change with additional enrollment and follow-up. The company cautioned that comparisons with autologous CAR T trials may not be meaningful because of differences in trial design, patient populations, products, and published data.
- ALLO-501 and ALLO-501A use Cellectis technology and are being developed with Servier. Allogene has exclusive U.S. rights, while Servier retains rights outside the United States.
Investor Verification Checklist
- Verify updated response rates, complete-response durability, survival, and safety outcomes as the ALPHA and ALPHA2 studies mature.
- Confirm the final ALLO-501A dose, consolidation schedule, Phase 2 design, regulatory feedback, and actual timing of Phase 2 initiation.
- Assess the significance of treatment-emergent deaths, serious infections, and other Grade 3 or higher adverse events with longer follow-up.
- Review the company’s Form 10-Q for the quarter ended March 31, 2021 for cash, liquidity, operating results, commitments, and risk factors not included in this 8-K.
- Confirm the scope of Allogene’s U.S. rights and Servier’s non-U.S. rights, as well as the company’s obligations under its Cellectis and Servier arrangements.