Express Milestones! Spot CAR-T therapies are entering critical clinical trials for the first time

▎Editor of WuXi AppTec content team

Recently, Allogene Therapeutics announced the commencement of its potentially critical Phase 2 clinical trial of the CAR-T therapy ALLO-501A, ALPHA2
。 According to the press release, this CAR-T therapy for the treatment of relapsed/refractory large B-cell lymphoma (LBCL) is the industry's first off-the-shelf CAR-T therapy to enter Phase 2 trials! In addition, Allogene is about to launch another EXPAND trial to see how its drug, ALLO-647, is improving the effectiveness
of allogeneic CAR-T therapy with a standard lymphatic removal protocol (fludarabine/cyclophosphamide).
If the trial results are positive, Allogene will discuss with the U.
S.
FDA the delivery of the listing application for
ALLO-501A and ALLO-647.

Large B-cell lymphoma is a non-Hodgkin lymphoma (NHL) that includes relapsed/refractory diffuse large B-cell lymphoma (DLBCL), marginal area lymphoma (MZL), primary mediastinal large B-cell lymphoma (PMBCL), grade 3B follicular lymphoma (FL3B), etc
.
Among them, diffuse large B cell lymphoma is the most common, with an average of 5.
6 people per 100,000 people diagnosed with diffuse large B cell lymphoma each year, and an average of 1.
8 people per 100,000 people dying from this cancer
.

ALL-501A is a genetically engineered AlloCAR-T product
targeting CD19.
ALLO-501A disrupts the TRAC and CD52 genes through TALEN gene editing technology to reduce the risk
of graft-versus-host disease (GvHD).
In addition, the genetic engineering of ALL-501A has allowed patients to use ALLO-647 for adjuvant therapy
.
ALLO-647 is a monoclonal antibody against CD52 that assists patients with selective and temporary host lymphocyte clearance to create an immune environment
in the patient that is more conducive to the growth of ALL-501A cells.
In June, the U.
S.
FDA awarded ALL-501A Regenerative Medicine Advanced Therapeutics (RMAT) for the treatment of relapsed/refractory large B-cell lymphoma
.

ALPHA2 is a single-armed, single-dose ALLO-501A (containing 120 million CAR-T cells) Phase 2 trial in which enrolled patients with relapsed/refractory large B-cell lymphoma are adjuvant therapy
with the FCA90 lymphocyte removal protocol (fludarabine/cyclophosphamide/90 mg ALLO-647).
The trial is expected to enroll approximately 100 patients
who have received at least 2 prior treatments and have not received targeted CD19 therapy.
The primary endpoint of the trial was objective response rate (ORR
).
On the other hand, the EXPAND trial is expected to enroll approximately 70 enrolled patients with relapsed/refractory large B-cell lymphoma and examine the role and safety of ALLO-647 in lymphocyte removal protocols
.
Patients receive the same dose of ALLO-501A as in the ALPHA2 trial and are randomly assigned to receive either a standard lymphocyte removal protocol (control group, without ALLO-647) or FCA90 lymphocyte removal protocol (containing 90 mg ALLO-647, the same as the ALPHA2 trial design).

The results of the Phase 1 clinical trial, presented at the American Academy of Hematology (ASH) Annual Meeting last December, showed good safety of ALLO-501A, with no safety issues
found in the trials related to dose-limiting toxicity (DLT), graft-versus-host disease and Grade 3 or above immune effector cell-associated neurotoxicity syndrome (ICANS) or grade 3 or above cytokine release syndrome (CRS).
。 In addition, in patients with large B-cell lymphoma who had not previously received CAR-T therapy, no relapse was observed after receiving a complete remission (CR) at 6 months of treatment, with the longest duration of complete remission exceeding 15 months
.
The median time from enrollment to initiation of treatment for all patients enrolled in this off-the-shelf ALLO-501A therapy was only 2 days, reflecting their potential
for rapid patient treatment.

"We are proud to have started the industry's first potentially critical Phase 2 clinical trial of an allogeneic CAR-T product! This milestone paves the way for the development of ALLO-501A and our other innovative products and pipelines, which will allow more patients to benefit from cell therapy," said Dr.
David Chang, co-founder, president and CEO of Allogene
.
”

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