Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage
biotechnology company pioneering the development of allogeneic CAR
T (AlloCAR T™) therapies for cancer, today announced positive
updated results from the Phase 1 UNIVERSAL study of single dose
ALLO-715 in relapsed/refractory (r/r) multiple myeloma. Data were
presented today in an oral session by Sham Mailankody, MBBS,
Assistant Attending Physician at Memorial Sloan Kettering Cancer
Center in New York, during the 63rd American Society of Hematology
(ASH) Annual Meeting in Atlanta. This study utilizes ALLO-647,
Allogene's anti-CD52 monoclonal antibody, as a part of its
differentiated lymphodepletion (LD) regimen.
“UNIVERSAL is the first study of an allogeneic anti-BCMA CAR T
to demonstrate safety and substantial efficacy in patients with
relapsed-refractory multiple myeloma,” said Dr. Mailankody.
“Safety, response and durability are on par with the approved
autologous CAR T therapy and appear to be superior to other readily
available therapies for multiple myeloma. This is especially
encouraging given the high percentage of penta-refractory patients
enrolled in the study. The data validates the feasibility of
ALLO-715 as an allogeneic, on demand CAR T product that may be an
option for patients with rapidly progressing disease and limited
treatment options.”
“We are encouraged by these updated findings from the UNIVERSAL
study that show a single dose of an off-the-shelf AlloCAR T product
is capable of inducing deep, clinically meaningful responses in
patients with r/r multiple myeloma,” said Rafael Amado, M.D.,
Executive Vice President of Research & Development and Chief
Medical Officer of Allogene. “This proof-of-concept data will form
the basis for evaluating anti-BCMA strategies that include
consolidated dosing of ALLO-715, ALLO-715 in combination with the
gamma secretase inhibitor nirogacestat, and ALLO-605, our
next-generation anti-BCMA TurboCAR™, with the goal of achieving
even better outcomes for patients with refractory myeloma.”
As of the October 14, 2021 data cutoff, 48 patients were
enrolled with 43 patients evaluable for safety and efficacy.
Patients were refractory to their last line of myeloma therapy, had
a median of five prior lines of therapy, and 42% were
penta-refractory meaning the disease has ultimately become
nonresponsive to other approved therapies. Five patients became
ineligible for treatment due to rapidly progressing disease. The
median time from enrollment to the start of therapy was five
days.
The Phase 1 UNIVERSAL trial evaluated lymphodepletion followed
by ALLO-715 at one of four dose levels (DL1=40M cells, DL2=160M
cells, DL3=320M cells, DL4 = 480M cells) and two LD regimens (FCA:
fludarabine, cyclophosphamide and ALLO-647 or CA: cyclophosphamide
and ALLO-647 only). The updated presentation primarily focuses on
the optimized DL3 cell dose and FCA lymphodepletion.
The higher CAR T cell doses were associated with an increased
response rate and greater AlloCAR T cell expansion. In the DL3
cohort which was selected for cohort expansion, the overall
response rate (ORR) increased from 60% reported at ASH 2020 to 71%
with 46% of patients achieving a very good partial response (VGPR)
or better (VGPR+) up from 40%. VGPR+ is defined as a stringent
complete response (sCR), complete response (CR) or VGPR. Of the
patients who achieved VGPR+, 92% were Minimal Residual Disease
(MRD) negative.
|
FCA |
Cell dose and LD regimen |
DL3 320 x 106 CAR+ cells |
Low ALLO-647(N=11) |
Mid ALLO-647(N=10) |
High ALLO-647(N=3) |
ALL ALLO-647(N=24) |
ORR, n (%) |
7 (64%) |
8 (80%) |
2 (67%) |
17 (71%) |
VGPR+ Rate, n (%) |
5 (46%) |
5 (50%) |
1 (33%) |
11 (46%) |
CR/sCR Rate, n (%) |
3 (27%) |
3 (30%) |
0 |
6 (25%) |
As of the data cutoff, the overall median follow-up for efficacy
was 3.8 months. The median duration of response is 8.3 months, with
nine patients remaining in ongoing response at the time of the data
cut-off. The longest ongoing response after cell infusion is 12
months. Results showed that soluble BCMA levels were 10 times lower
in responders at Day 28, suggesting soluble BCMA suppression is
associated with response.
Of the 43 patients evaluable for safety, there was no
graft-versus-host-disease (GvHD). Grade 1 and 2 cytokine release
syndrome (CRS) was reported in 23 patients (53%) and was manageable
with standard therapies. In this heavily pre-treated patient
population, infection occurred in 54% of patients, which included
three Grade 5 infections, two of which were previously reported.
Grade 3+ neutropenia occurred in 70% of patients. Six patients
(14%) experienced adverse events of low-grade neurotoxicity, which
was reversible. Use of tocilizumab and steroids was infrequent (23%
and 14%, respectively).
Adverse Events of Interest |
Grade 1N (%) |
Grade 2N (%) |
Grade 3N (%) |
Grade 4N (%) |
Grade 5N (%) |
All GradesN (%) |
CRS |
13 (30%) |
10 (23%) |
1 (2%) |
0 |
0 |
24 (56%) |
Neurotoxicity |
4 (9%) |
2 (5%) |
0 |
0 |
0 |
6 (14%) |
GvHD |
0 |
0 |
0 |
0 |
0 |
0 |
Infection |
3 (7%) |
10 (23%) |
7 (16%) |
0 |
3 (7%) |
23 (54%) |
Infusion Reaction to ALLO-647 |
7 (16%) |
5 (12%) |
0 |
0 |
0 |
12 (28%) |
ALLO-715 has been granted Regenerative Medicine Advanced Therapy
(RMAT) designation by the FDA for the treatment of r/r multiple
myeloma.
As part of the Company’s anti-BCMA strategy, the UNIVERSAL trial
is also studying consolidated dosing of ALLO-715 using ALLO-647 to
selectively extend the window of lymphodepletion. UNIVERSAL is also
evaluating ALLO-715 in combination with SpringWorks Therapeutics’
investigational gamma secretase inhibitor, nirogacestat. The Phase
1 dose escalation portion of the IGNITE trial evaluating ALLO-605,
the Company’s first TurboCAR™ candidate, was initiated in Q2 2021.
TurboCAR technology allows cytokine activation signaling to be
engineered selectively into CAR T cells and has shown the ability
to improve the potency and persistence of allogeneic cells in
preclinical models. Subject to the clinical hold currently in
place, Allogene continues to target 2022 for data from these
additional strategies.
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-715ALLO-715, an AlloCAR T therapy
targeting B-cell maturation antigen (BCMA), is a potential novel
treatment for multiple myeloma and other BCMA-positive
malignancies. Multiple myeloma originates in the bone marrow. It is
characterized by abnormalities in plasma cells that reproduce
uncontrollably in the bone marrow and other disease sites. Multiple
myeloma is incurable for most patients, as relapses occur despite
most treatments available. ALLO-715 was granted Regenerative
Medicine Advanced Therapy (RMAT) designation in April 2021 and
Orphan Drug Designation (ODD) in August 2021 by the U.S. Food and
Drug Administration (FDA). The Phase 1 UNIVERSAL trial is 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 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," "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 and timing to progress the UNIVERSAL trial and
IGNITE trial and present any data from the trials; 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 Berdeja, Lancet, 2021 and Munshi, NEJM, 2021. 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 trial of the approved autologous CAR T
product 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 technology.
ALLO-715 and ALLO-605 target BCMA. 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.
Allogene Media/Investor Contact:Christine
CassianoChief Communications Officer(714)
552-0326Christine.Cassiano@allogene.com
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