Allogene Therapeutics CD19 Forum Highlights Positive Results from Phase 1 Studies of ALLO-501 and ALLO-501A in Relapsed/Refractory Non-Hodgkin Lymphoma and Plan to Initiate Pivotal Study in 2021
- ALLO-501 ALPHA Trial Produced Durable Complete Responses (CR) with Longest Ongoing CR at 15 Months in Both Large B Cell Lymphoma (LBCL) and Follicular Lymphoma (FL)
- Overall Response Rate (ORR) of 75% and CR Rate of 50% Across Histologies in CAR T Naïve Patients, on Par with Data from Pivotal Trials of Autologous CAR T Therapies
- Six Month CR Rate of 36% with One Time Treatment in CAR T Naïve Patients with LBCL
- 98% of Enrolled Patients Received ALLO-501 With a Median Time of 5 Days from Enrollment to Start of Therapy
- Interim Phase 1 ALPHA2 Data Demonstrated a Comparable Efficacy and Safety Profile for ALLO-501A Relative to ALLO-501
- Consolidation Dosing was Well Tolerated and Shows Early Promise with Four Patients Converting from Partial Response (PR) to CR Following Second Dose of ALLO-501 or ALLO-501A
- No Dose Limiting Toxicities or Graft-vs-Host Disease; Limited Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and Cytokine Release Syndrome (CRS)
- Safety and PK/PD Data of ALLO-647 with Flu/Cy Across ALPHA, ALPHA2 and UNIVERSAL (ALLO-715 in Multiple Myeloma) Trials Demonstrated Manageable Safety Profile; Exposure-Dependent Deep Lymphodepletion Correlated with AlloCAR T Cell Expansion and Clinical Responses
- Initiation of Pivotal Trial of ALLO-501A Planned for Late 2021
- Two Posters to be Presented at the Annual Meeting of the
American Society of Clinical Oncologyon June 4, 2021on ALLO-501, ALLO-501A and ALLO-647
- Company to Host
May 19 Virtual CD19 Forumat 5:30 PM Eastern Time
These data will also be featured in poster presentations at the 2021
“We are delighted to present updated data on what we believe to be the most advanced allogeneic CAR T program in development. Longer-term data from the ALPHA trial of ALLO-501 in combination with ALLO-647 demonstrate for the first time the ability of an off-the-shelf cell therapy to induce durable responses in NHL patients similar to that seen in trials of autologous therapies,” said
The Forum will include a panel of leading physicians discussing perspectives on the future of allogeneic CAR T therapy in NHL. The panel, moderated by
Lazaros J. Lekakis, M.D, Associate Professor of Clinical Medicine, Transplantation and Cellular Therapy, Sylvester Cancer Center, University of Miami Frederick L. Locke, M.D., Co-Leader, Moffitt Immuno-Oncology Program, Vice Chair and Associate Member Department of Blood and Marrow Transplantand Cellular Immunotherapy, Moffitt Cancer Center Michael Tees, M.D., M.P.H., Associate Member Physician, Colorado Blood Cancer Institute, Sarah Cannon Research Institute
“Our vision for allogeneic cell therapy is to go beyond the boundaries of autologous products and establish new standards for CAR T therapy that, anchored on fundamentals of allogeneic cell therapy, fully explore the unique benefits of an off-the-shelf product including consolidation dosing. We believe the data presented today demonstrates our ability to shape, define and advance the field of CAR T therapy, and we look forward to potentially moving toward a pivotal trial for ALLO-501A in late 2021,” said
Phase 1 ALLO-501 ALPHA Trial
As of the
Responses were observed across all cell doses and tumor histologies (large B-cell lymphoma (LBCL) and follicular lymphoma (FL)). In CAR T naïve patients, response rates were similar to those seen in autologous CAR T therapy trials:
|LBCL (N=11)||FL (N=21)||All Patients (N=32)|
The percent of these patients remaining in complete response at six months following a single infusion was 29%, with 36% in LBCL and 24% in FL. Data reported following the data cutoff to
ALLO-647 was used in lymphodepletion with fludarabine (Flu)/cyclophosphamide (Cy) at doses ranging from 39mg to 90mg.
|ALLO-647 39 mg
|ALLO-647 60 mg
|ALLO-647 90 mg
|All Patients (N=41)|
|All Gr||Gr 3+||All Gr||Gr 3+||All Gr||Gr 3+||All Gr||Gr 3+|
|IRR||5 (46%)||-||3 (50%)||-||18 (75%)||1 (4)||26 (63%)||1 (2%)|
|CRS||2 (18%)||-||1 (17%)||-||8 (33%)||-||11 (27%)||-|
|ICANS||-||-||-||-||1 (4%)||1 (4%)||1 (2%)||1 (2%)|
|Infection||7 (64%)||1 (9%)||1 (17%)||1 (17%)||17 (71%)||8 (33%)||25 (61%)||10 (24%)|
No dose limiting toxicities or graft-vs-host disease (GvHD) were observed and one (2%) case of Grade 3 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was reported. Cytokine release syndrome (CRS) occurred in 27% of patients, was limited to Grade 1 or 2, and was manageable with standard protocols. Infection rates were similar to those observed in autologous CAR T trials. During this study, there were five treatment-emergent deaths in the absence of disease progression, one each from fungal pneumonia, arrythmia, and stroke, and two instances of COVID-19 acquired in the community setting. Three of these patients were in ongoing CR at the time of death.
Phase 1 ALLO-501A ALPHA2 Trial
ALLO-501A is a next generation anti-CD19 AlloCAR T candidate intended for Phase 2 development and is engineered without the rituximab recognition domains found in ALLO-501. The Phase 1 dose escalation portion of the ALPHA2 trial was designed to confirm that the profile of ALLO-501A is similar to ALLO-501 prior to advancing ALLO-501A into Phase 2. This trial is only enrolling patients with relapsed/refractory LBCL.
Following promising efficacy data from patients (N=4) treated at dose level 2 (120 x 106 CAR+ cells; DL2), patient enrollment in ALPHA2 focused on exploration of a consolidated dosing strategy that enabled patients who did not progress following an initial dose of ALLO-501A to receive a second, scheduled dose of cells. In consolidation dosing, 60mg ALLO-647 was provided with Flu/Cy for lymphodepletion before the first cell administration at DL2, and 30mg ALLO-647 with no Flu/Cy was provided for lymphodepletion before the second cell infusion at DL2 to patients with selective hematologic criteria.
As of the
|DL2 (N=4)||Consolidation (N=5)||All Patients (N=9)|
No dose limiting toxicities, GvHD or ICANS were observed in ALPHA2.
40 x 106 (40M)
120 x 106 (120M)
CAR+ cells (N=5)
(120M + 120M)
|All Patients (N=13)*|
|All Gr||Gr 3+||All Gr||Gr 3+||All Gr||Gr 3+||All Gr||Gr 3+|
|IRR||1 (100%)||-||2 (40%)||-||2 (33%)||-||5 (39%)||-|
|CRS||1 (100%)||1 (100%)||1 (20%)||-||-||-||2 (15%)||1 (8%)|
|Infection||1 (100%)||-||4 (80%)||1 (20%)||2 (33%)||-||7 (54%)||1 (8%)|
* One patient was treated with ALLO-647 but not ALLO-501A and deemed unable to proceed to cell infusion.
The Company plans to collect additional data from the consolidation arms of the ALPHA and ALPHA2 studies, finalize a dose and schedule of ALLO-501A and lymphodepletion for a potential Phase 2 trial, and discuss the Phase 2 trial design with regulatory authorities. Pending the collection of data and regulatory feedback, the Company plans to move to the Phase 2 portion of ALPHA2 by the end of 2021.
ALLO-647 Consolidated Safety and PK/PD Analysis
The safety and PK/PD profile of ALLO-647 was evaluated as part of a proprietary lymphodepletion regimen that also deploys Flu/Cy. Patients treated as part of the ALPHA, ALPHA2 and UNIVERSAL (anti-BCMA candidate ALLO-715 in relapsed/refractory multiple myeloma) trials were included in the analyses.
The data show that ALLO-647, when used in combination with Flu/Cy, induced deep, durable exposure-dependent lymphodepletion. Lymphodepletion is designed to provide a window for AlloCAR T persistence, and exposure to ALLO-647 correlated with lymphocyte depletion, CAR T cell expansion and greater clinical response. ALLO-647 in combination with Flu/Cy had a manageable safety profile with rates of Grade 3 infection similar to autologous CAR T therapies.
ALPHA (N=41) & ALPHA2 (N=13)
|ALLO-647 Dose||39 mg
|FCA60 & Consolidation
|ALL TEAES+||22 (100%)||9 (100%)||3 (100%)||11 (100%)||13 (93%)||8 (89%)||29 (100%)|
|Grade 3 AEs||2 (9%)||3 (33%)||-||-||2 (14%)||1 (11%)||7 (24%)|
|All Infection++||12 (55%)||6 (67%)||1 (33%)||7 (64%)||4 (29%)||3 (33%)||21 (72%)|
|Grade 3 Infection||5 (23%)||4 (44%)||-||1 (9%)||2 (14%)||1 (11%)||8 (28%)|
|Infusion Related Reaction to ALLO-647 (All Grades)||6 (27%)||2 (22%)||1 (33%)||5 (45%)||6 (43%)||4 (44%)||20 (69%)|
|Grade 3 Hematologic AEs|
|Anemia||7 (32%)||2 (22%)||-||2 (18%)||3 (21%)||-||12 (41%)|
|Thrombocytopenia||6 (27%)||3 (33%)||1 (33%)||3 (27%)||5 (36%)||2 (22%)||14 (48%)|
|Neutropenia||11 (50%)||6 (67%)||2 (67%)||9 (82%)||8 (57%)||4 (44%)||21 (72%)|
+Number of patients with AE occurring from the start of study drug up to subsequent anti-cancer therapy. For patients reporting more than one AE within a preferred term, only one AE with the maximum grade is reported.
++All infections (bacterial, fungal, and viral) included.
The UNIVERSAL trial, which enrolled heavily pre-treated myeloma patients, including those with rapidly progressing disease, included two Grade 5 events. One previously disclosed event was attributed to progressive myeloma and lymphodepletion with cyclophosphamide and ALLO-647. The second was a 78-year-old male, heavily pretreated and with ongoing lymphopenia prior to therapy, who had adenovirus reactivation.
ALLO-715 was recently granted Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA for the treatment of relapsed refractory multiple myeloma.
About ALLO-501 (Allogene Sponsored)
ALLO-501 is an anti-CD19 allogeneic CAR T (AlloCAR T™) therapy being jointly developed under a collaboration agreement between
About ALLO-501A (Allogene Sponsored)
ALLO-501A, a next-generation anti-CD19 AlloCAR T™ intended for Phase 2 development, eliminates the rituximab recognition domains in ALLO-501, which could allow for use in a broader patient population, including NHL patients with recent rituximab exposure. Like ALLO-501, ALLO-501A is being jointly developed under a collaboration agreement between
Cautionary Note on Forward-Looking Statements for Allogene
This press release contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. The press release may, in some cases, use terms such as "predicts," "believes," "potential," "proposed," "continue," "estimates," "anticipates," "expects," "plans," "intends," "may," "could," "might," "will," "should" or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. Forward-looking statements include statements regarding intentions, beliefs, projections, outlook, analyses or current expectations concerning, among other things: the timing and ability to progress the ALPHA and ALPHA2 trials, including progressing to the Phase 2 portion of the ALPHA2 trial; clinical outcomes, which may materially change as patient enrollment continues and more patient data become available; and the potential benefits of AlloCAR T™ therapy and the Company’s lymphodepletion strategy. Various factors may cause differences between Allogene’s expectations and actual results as discussed in greater detail in Allogene’s filings with the Securities and Exchange Commission (SEC), including without limitation in its Form 10-Q for the quarter ended March 31, 2021. Any forward-looking statements that are made in this press release speak only as of the date of this press release. Allogene assumes no obligation to update the forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
Statements regarding autologous CAR T data are based on review of Kymriah United States product insert (USPI), Schuster S et
AlloCAR T™ is a trademark of Allogene Therapeutics, Inc.
Allogene’s AlloCAR T programs utilize Cellectis technologies. ALLO-501 and ALLO-501A are anti-CD19 allogeneic CAR T (AlloCAR T™) therapies being jointly developed under a collaboration agreement between Servier1 and Allogene based on an exclusive license granted by Cellectis to Servier. Servier grants to Allogene exclusive rights to ALLO-501 and ALLO-501A in the U.S. while Servier retains exclusive rights for all other countries.
Allogene has an exclusive license to the Cellectis technology for allogeneic products directed at BCMA and holds all global development and commercial rights for these investigational candidates.
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Source: Allogene Therapeutics, Inc.