Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage
biotechnology company pioneering the development of allogeneic CAR
T (AlloCAR T™) products for cancer, today announced the
presentation of data from a comprehensive safety review of patients
treated in the Phase 1 ALPHA/ALPHA2 trials with ALLO-501/501A at
the 65th Annual Meeting of the American Society of Hematology (ASH)
in San Diego, CA.
The safety review, which encompasses all 87 Phase 1 patients
treated in both relapsed/refractory (r/r) Large B Cell Lymphoma
(LBCL) and follicular lymphoma (FL), demonstrates that
investigational ALLO-647 added to standard lymphodepletion can
safely provide a window for the expansion and persistence of
AlloCAR T cells, and has the potential to induce deep and durable
remissions in relapsed and treatment-refractory cancers.
"We believe in the immense potential of off-the-shelf CAR T
products to not only address the limitations of current autologous
CAR T cell therapy, but to also provide greater access to patients
in need,” said Zachary Roberts, M.D., Ph.D., Executive Vice
President of Research & Development and Chief Medical Officer
of Allogene. “We fully understand the importance of lymphodepletion
to achieving optimal outcomes, and ALLO-647 is just the first
generation of our innovative approaches to enhancing
lymphodepletion to promote expansion of CAR T cells.”
The inclusion of our ALLO-647 candidate in the lymphodepletion
regimen is designed to selectively prevent host rejection of
allogeneic CAR T cell products. As previously presented in the
Phase 1 ALPHA/ALPHA2 studies1, CAR T cell-naive patients with r/r
LBCL were able to obtain a durable response, including a complete
remission rate of 42% and a median duration of response of 23.1
months.
In the studies, lymphodepletion consisted of three daily doses
of fludarabine 30 mg/m2 and cyclophosphamide 300-500
mg/m2 (FC) and 39, 60, or 90 mg of ALLO-647 in divided doses
prior to ALLO-501/501A infusion. The addition of ALLO-647 to
standard lymphodepletion did not result in adverse events beyond
those commonly observed with autologous CAR T cell
therapy.
No unexpected safety concerns were observed. Neutropenia and
anemia were the most common any-grade treatment-emergent adverse
events (or TEAEs) and neutropenia, anemia, and thrombocytopenia
were the most common Grade 3 or higher TEAEs. Grade 3 or higher
cytopenias decreased over time from Day 28 to Month 4 and were
consistent across all subsets of patients. Incidence of Grade 3 or
higher cytopenias were consistent with that reported for autologous
CAR T cell therapy.2-4
Safety: TEAEs of Special Interest
TEAEs, n (%) |
All (N=87) |
LBCL |
FL (n=26) |
All LBCL (n=61) |
CAR T Cell–Naive Pts Who ReceivedALLO-501/501A Manufactured
WithThe Phase 2 Selected Process (n=33) |
Any Grade |
Grade ≥3 |
Any Grade |
Grade ≥3 |
Any Grade |
Grade ≥3 |
Any Grade |
Grade ≥3 |
CRS |
21 (24) |
1 (1) |
17 (28) |
1 (2) |
8 (24) |
0 |
4 (15) |
0 |
ICANS |
1 (1) |
0 |
1 (2) |
0 |
0 |
0 |
0 |
0 |
Neurotoxicity |
24 (28) |
3 (3) |
19 (31) |
3 (5) |
13 (39) |
2 (6) |
5 (19) |
0 |
GvHD |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
IRR |
48 (55) |
5 (6) |
31 (51) |
4 (7) |
16 (48) |
3 (9) |
17(65) |
1 (4) |
Infections |
50 (57) |
18 (21) |
34 (56) |
13 (21) |
19 (58) |
5 (15) |
16 (62) |
5 (19) |
There were no reports of graft-versus-host disease (GvHD) or
Grade 3 or higher immune effector
cell-associated neurotoxicity syndrome (ICANS). In total, 24%
of patients experienced low-grade CRS, and there was 1 Grade 3 CRS
event. Infection events were primarily low grade and manageable,
with the most common being cytomegalovirus reactivation with an
any-grade incidence of 25% and a Grade 3 or higher incidence of 9%.
Incidence of infections were consistent with that reported for
autologous therapy following lymphodepletion (12%-33% percent of
patients).3-5 Eight patients experienced fatal adverse events not
related to study treatment.
The EXPAND trial, currently enrolling in the United
States and Europe, is expected to support licensure of
ALLO-647, used in conjunction with standard low-dose FC
lymphodepletion regimens. The trial will enroll approximately 70
patients with r/r LBCL who will be randomized to lymphodepletion
with FCA90 (which includes 90 mg of ALLO-647) versus FC alone
before receiving a single 120 million cell dose of ALLO-501A. The
primary endpoint of the study is progression free survival
(PFS).
Separately, the Company announced that the U.S. Food and Drug
Administration (FDA) granted Fast Track Designation (FTD) for the
investigation of ALLO-647 in adult patients with r/r LBCL based on
its potential to enhance standard lymphodepletion. FTD designation
is intended to accelerate the development and review of treatments
for serious and life-threatening diseases where no treatment exists
or where the treatment in discovery may be better than what is
currently available. ALLO-647 is investigated as a lymphodepleting
agent in combination with flu/cy prior to infusion of allogeneic
CD19-directed CAR T cells with genomes edited to knock out
CD52.
About ALLO-501 and ALLO-501AALLO-501 and
ALLO-501A are anti-CD19 AlloCAR TTM investigational products for
the treatment of large B cell lymphoma. ALLO-501A, a
next-generation anti-CD19 AlloCAR TTM product, 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. This product candidate is currently
being studied in an ongoing potentially pivotal Phase 2 trial. In
June 2022, the U.S. Food and Drug Administration granted
Regenerative Medicine Advanced Therapy (RMAT) designation to
ALLO-501A in r/r LBCL.
About Allogene TherapeuticsAllogene
Therapeutics, with headquarters in South San Francisco, is a
clinical-stage biotechnology company pioneering the development of
allogeneic chimeric antigen receptor T cell (AlloCAR T™) products
for cancer. Led by a management team with significant experience in
cell therapy, Allogene is developing a pipeline of “off-the-shelf”
CAR T product candidates with the goal of delivering readily
available cell therapy on-demand, more reliably, and at greater
scale to more patients. For more information, please
visit www.allogene.com, and follow @AllogeneTx on X (formerly
Twitter) and LinkedIn.
Cautionary Note on Forward-Looking Statements
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," “can,” "could," "might," "will," "should,”
“designed to” 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: Allogene’s ability to deliver
readily available off-the shelf cell therapy on-demand, more
reliably, and at greater scale to more patients; the potential
safety profile of the Company’s lymphodepletion and cell dose
regimen; and the modes of action, the therapeutic effects and
safety profile of Allogene’s product candidates including their
ability to treat cancers at various stages or to treat broad
populations. Various factors may cause material differences between
Allogene’s expectations and actual results, including risks and
uncertainties related to: our product candidates are based on novel
technologies, which makes it difficult to predict the time and cost
of product candidate development and obtaining regulatory approval;
the FDA may disagree with our regulatory plan and we may fail to
obtain regulatory approval of our CAR T cell product candidates;
and our clinical trials may fail to demonstrate the safety and
efficacy of any of our product candidates, which would prevent or
delay regulatory approval and commercialization. These and other
risks are discussed in greater detail in Allogene’s filings with
the SEC, including without limitation under the “Risk Factor”
Heading in its Form 10-Q filed for the quarter ended September
30, 2023, being filed with the SEC today. 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.
Caution should be exercised regarding statements comparing
autologous CAR T data. There are differences in the clinical trial
design, patient populations, published data, follow-up times and
the product candidates themselves, and the results from the
clinical trials of autologous products may have no interpretative
value on Allogene’s existing or future results.
AlloCAR T™ and Alloy™ are trademarks of Allogene
Therapeutics, Inc.
Allogene’s AlloCAR T™ programs utilize Cellectis technologies.
ALLO-501 and ALLO-501A are anti-CD19 products being jointly
developed under a collaboration agreement between Servier 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.
1. Locke FL, Lekakis L, Eradat H, et al. Durable Responses with
Anti-CD19 Allogeneic CAR T ALLO-501/501A in Phase 1 Trials of
Relapsed/Refractory Large B-Cell Lymphoma (r/r LBCL). Oral
presentation at the International Conference on Malignant Lymphoma.
June 13-17, 2023. Abstract 48. 2. Logue JM, et al. Haematologica.
2021;106(4):978-986. 3. KYMRIAH. Prescribing Information. Novartis
Pharmaceuticals Corp.; 2022. 2022. 4. BREYANZI. Prescribing
Information. Juno Therapeutics, Inc.;5. YESCARTA. Prescribing
information. Kite Pharma, Inc; 2022.
Allogene Media/Investor Contact:Christine
CassianoEVP, Chief Corporate Affairs & Brand Strategy
OfficerChristine.Cassiano@allogene.com
Additional Allogene Media Contacts:Leslie
BryantLeslie.Bryant@allogene.com
Madeleine GoldsteinMadeleine.Goldstein@allogene.com
Allogene Therapeutics (NASDAQ:ALLO)
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