Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage
biotechnology company pioneering the development of allogeneic CAR
T (AlloCAR T™) therapies for cancer, today reported updated data
from two Phase 1 clinical trials (ALPHA and ALPHA2) of its lead
anti-CD19 AlloCAR T therapy programs (ALLO-501 and ALLO-501A) at
the 63rd American Society of Hematology (ASH) Annual Meeting.
ALLO-501 (ALPHA) data in patients with relapsed/refractory (r/r)
large B cell lymphoma (LBCL) or follicular lymphoma (FL) were
presented in a poster session by Sattva S. Neelapu, M.D., of The
University of Texas MD Anderson Cancer Center. ALLO-501A (ALPHA2)
data in patients with r/r LBCL were presented in an oral session by
Lazaros J. Lekakis, M.D., of the Sylvester Comprehensive Cancer
Center, University of Miami Health System.
“Data from our ALPHA and ALPHA2 trials continue to validate the
promise of our AlloCAR T platform to be a safe and durable
alternative to approved autologous CAR T therapies,” said Rafael
Amado, M.D., Executive Vice President of Research & Development
and Chief Medical Officer of Allogene. “We are excited to leverage
the combined learnings from these studies, including the potential
advantages of consolidation dosing, as we continue to prepare for a
pivotal Phase 2 clinical trial with ALLO-501A for the treatment of
relapsed/refractory non-Hodgkin lymphoma.”
“Results from the ALPHA study presented at the 2021 ASH Annual
Meeting confirm that ALLO-501 can be safely, effectively and
conveniently delivered to LBCL and FL patients, with durable
responses observed in both lymphoma subtypes. These data are on par
with autologous CAR T therapy and suggest that an off-the-shelf
product could be a promising option for patients with
relapsed/refractory NHL,” said Dr. Neelapu.
“The ALPHA2 study demonstrates the ability of ALLO-501A to
induce deep and durable responses in relapsed/refractory LBCL
patients. Consolidation 1 dosing was well tolerated with lower
rates of cytopenias and infection while maintaining a similar
complete response rate as autologous CAR T therapy. This regimen
provides the potential for enhanced efficacy as well as use in an
outpatient setting by virtue of its favorable safety profile,” said
Dr. Lekakis.
|
ALPHA |
ALPHA2 |
Data Cutoff |
October 18, 2021 |
Enrolled |
50 |
29 |
Evaluable for Safety |
49* |
28** |
Evaluable for Efficacy |
40# |
25† |
% Initiated Treatment |
98% |
97% |
Median Days Enrollment to Treatment Initiation |
5 |
2 |
* One patient unable to be treated due to rapidly progressing
disease** One patient developed COVID-19 before treatment# Only CAR
T Naïve subjects presented from ALPHA at ASH 2021†One patient
started LD but became ineligible due to central nervous system
disease progression; two treated patients yet to reach tumor
assessment at data cutoff
Patients received lymphodepletion (LD) containing fludarabine
(30mg/m2 x 3 days), cyclophosphamide (Cy) (300mg/m2 x 3 days) and
ALLO-647 (30, 60 or 90mg) followed by escalating doses of ALLO-501
or ALLO-501A. In consolidation, patients with stable disease or
better at Day 28 received a chemotherapy-free lymphodepletion
(ALLO-647 only) and AlloCAR T cell infusion (120 x 106 CAR+ T
cells). The trials explored two consolidation cohorts.
Consolidation 1 used the standard Cy dosing (300mg/m2 x 3 days).
Consolidation 2 explored a higher Cy dose (500mg/m2 x 3 days).
Response Rates Across the ALPHA and ALPHA2
Trials
ALPHA ALLO-501 Response Rates
|
Follicular Lymphoma (FL) |
Large B Cell Lymphoma (LBCL) |
|
|
Single dose (N=18) |
Cons(N=8) |
All FL(N=26) |
Single dose(N=11) |
Cons(N=3) |
All LBCL(N=14) |
All Patients(N=40) |
ORR, n (%) |
14 (78%) |
7 (88%) |
21 (81%) |
7 (64%) |
2 (67%) |
9 (64%) |
30 (75%) |
CR, n (%) |
9 (50%) |
6 (75%) |
15 (58%) |
5 (45%) |
1 (33%) |
6 (43%) |
21 (53%) |
Consolidation 1 and 2 combined due to limited sample size at the
time of the data cutoff
Among the 21 FL patients and 11 LBCL patients who were
autologous CAR T naïve, 33% and 36% achieved a complete response at
six months. With the exception of one previously disclosed patient
who died from unrelated arrhythmia, all LBCL patients who achieved
a CR at month six remain in CR with the longest ongoing CR at 18+
months.
ALPHA2 ALLO-501A Response Rates
|
DL1/DL2 (N=6) |
Cons 1(N=9) |
Cons 2(N=10) |
All Patients(N=25) |
ORR, n (%) |
2 (33%) |
4 (44%) |
6 (60%) |
12 (48%) |
CR, n (%) |
2 (33%) |
4 (44%) |
1 (10%) |
7 (28%) |
Longest CR (months) |
15+ |
9+ |
4+ |
15+ |
All patients who achieved a CR at month six remain in CR with
the longest ongoing CR at 15+ months and longest ongoing CRs in the
consolidation cohort at 9+ months. Combined ALPHA + ALPHA2
Consolidation Response Rates
|
Consolidation 1 |
Consolidation 2 |
All Patients |
|
N = 16 |
N = 14 |
N = 30 |
ORR, n (%) |
9 (56%) |
10 (71%) |
19 (63%) |
CR, n (%) |
7 (44%) |
5 (36%) |
12 (40%) |
Consolidation dosing was associated with meaningful cell
expansion after the second dose of AlloCAR T cells. As noted in the
ALPHA response rate table, consolidation was associated with a
higher ORR (88% vs. 78%) and CR rate (75% vs. 50%) in FL patients
versus a single dose of ALLO-501. All seven FL patients who
responded to consolidation remain in response with the longest
ongoing response at seven months. In the combined Consolidation 1
cohort, four partial responses (PR) converted to CR following the
second administration of cells with six of the seven patients in
this regimen who achieved CRs remaining in CR.
Safety Across the ALPHA and ALPHA2 Trials
AlloCAR T therapy was associated with consistent and manageable
safety with no dose limiting toxicities (DLTs) or graft-vs-host
disease (GvHD), and minimal Grade 3 Immune Effector Cell-Associated
Neurotoxicity Syndrome (ICANS), or Grade 3 cytokine release
syndrome (CRS). Consolidation 1 presented a superior safety profile
across all cohorts.
ALPHA ALLO-501 Safety
|
DL1 40M (N=4) |
DL2 120M (N=16) |
DL3 360M (N=16) |
Cons (N=11) |
All Patients (N=49) |
|
All |
Gr3+ |
All |
Gr3+ |
All |
Gr3+ |
All |
Gr3+ |
All |
Gr3+ |
IRR |
50 |
% |
0 |
|
69 |
% |
6 |
% |
61 |
% |
0 |
|
64 |
% |
18 |
% |
63 |
% |
6 |
% |
CRS |
0 |
|
0 |
|
31 |
% |
6 |
% |
33 |
% |
0 |
|
27 |
% |
9 |
% |
29 |
% |
4 |
% |
Neurotoxicity |
25 |
% |
0 |
|
25 |
% |
6 |
% |
22 |
% |
0 |
|
36 |
% |
9 |
% |
27 |
% |
4 |
% |
GvHD |
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
Infection |
75 |
% |
0 |
|
63 |
% |
38 |
% |
61 |
% |
17 |
% |
64 |
% |
36 |
% |
63 |
% |
27 |
% |
Neutropenia |
100 |
% |
75 |
% |
75 |
% |
75 |
% |
83 |
% |
72 |
% |
82 |
% |
64 |
% |
82 |
% |
71 |
% |
Serious AE |
25% |
56% |
28% |
27% |
37% |
Grade 3+ infection rates were observed at a rate similar to that
seen in autologous CAR T trials. There were five treatment-emergent
deaths in the absence of disease progression, all of which were
previously reported.
ALPHA2 ALLO-501A Safety
|
DL1 40M(N=1) |
DL2 120M (N=6) |
Cons 1 (N=11) |
Cons 2(N=10) |
All Patients (N=28) |
|
All Gr |
Gr 3+ |
All Gr |
Gr 3+ |
All Gr |
Gr 3+ |
All Gr |
Gr 3+ |
All Gr |
Gr 3+ |
IRR |
100 |
% |
0 |
33 |
% |
0 |
|
27 |
% |
0 |
|
10 |
% |
0 |
|
25 |
% |
0 |
|
CRS |
100 |
% |
0 |
17 |
% |
0 |
|
0 |
|
0 |
|
10 |
% |
0 |
|
11 |
% |
0 |
|
Neurotoxicity |
100 |
% |
0 |
33 |
% |
0 |
|
9 |
% |
0 |
|
20 |
% |
0 |
|
21 |
% |
0 |
|
GvHD |
0 |
|
0 |
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
0 |
|
Infection |
100 |
% |
0 |
83 |
% |
17 |
% |
27 |
% |
0 |
|
10 |
% |
10 |
% |
36 |
% |
7 |
% |
Neutropenia |
0 |
|
0 |
100 |
% |
100 |
% |
36 |
% |
36 |
% |
60 |
% |
60 |
% |
57 |
% |
57 |
% |
Serious AE |
0 |
100% |
18% |
30% |
39% |
The safety profile of ALLO-501A was manageable in both the
single-dose and both consolidation cohorts. There were no
treatment-emergent deaths in the trial. Adverse events of interest
in the single-dose cohort were previously reported at the 2021
American Society of Clinical Oncology (ASCO) Annual Meeting. A
chromosomal abnormality is being investigated in a patient in
Consolidation 2, which has resulted in a clinical hold on the ALPHA
and ALPHA2 trials.
Pending resolution of the clinical hold and ongoing discussion
with the U.S. Food and Drug Administration (FDA), the Company
intends to initiate a Phase 2 pivotal trial in r/r LBCL utilizing
the Consolidation 1 dosing regimen. In the ALPHA and ALPHA2 trials,
this regimen was easy to administer and associated with a favorable
safety profile, CR rates on par with autologous CAR T therapies,
and supportive biomarker data.
Conference Call and Webcast DetailsAllogene
will host a live conference call and webcast today, Monday December
13, at 1:30 p.m. Pacific Time / 4:30 p.m. Eastern Time to discuss
Allogene data presented at ASH. To access the live conference call
by telephone, please dial 1 (866) 940-5062 (U.S.) or 1 (409)
216-0618 (International). The conference ID number for the live
call is 1281484. The webcast will be made available on the
Company's website at www.allogene.com under the Investors tab in
the News and Events section. Following the live audio webcast, a
replay will be available on the Company's website for approximately
30 days.
About ALLO-501/ALLO-501A (Allogene
Sponsored)ALLO-501 and ALLO-501A are anti-CD19 allogeneic
CAR T (AlloCAR T™) products in development for the treatment of
relapsed or refractory non-Hodgkin’s lymphoma (NHL). 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.
The ALPHA study of ALLO-501 and the ALPHA2 study of ALLO-501A are
currently on clinical hold by the FDA.
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™) therapies
for cancer. Led by a management team with significant experience in
cell therapy, Allogene is developing a pipeline of “off-the-shelf”
CAR T cell therapy 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 Twitter and
LinkedIn.
Cautionary Note on Forward-Looking
StatementsThis 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 ability to progress the ALPHA2
trial and proceed to the Phase 2 portion of the trial; clinical
outcomes, which may materially change as more patient data become
available; the ability to resolve the current clinical hold on the
Company’s trials; and the potential benefits of AlloCAR T™ therapy.
Various factors may cause differences between Allogene’s
expectations and actual results as discussed in greater detail in
Allogene’s filings with the SEC, including without limitation
in its Form 10-Q for the quarter ended September 30, 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 al
NEJM 2019; Yescarta USPI, Locke, AACR 2017; and Breyanzi USPI.
Caution should be exercised when interpreting results from separate
trials involving separate product candidates. 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 our existing or future results.
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 products 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 Media/Investor Contact:Christine
CassianoChief Communications Officer(714)
552-0326Christine.Cassiano@allogene.com
1 Servier is an independent international pharmaceutical company
governed by a non-profit foundation, with its headquarters in
France (Suresnes).
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