Allogene Therapeutics R&D Showcase Features Hematologic and Solid Tumor Advances Acro | ALLO Message Board Posts

Allogene Therapeutics, Inc.

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Msg  5 of 6  at  11/30/2022 8:49:15 PM  by


Allogene Therapeutics R&D Showcase Features Hematologic and Solid Tumor Advances Acro

 Pharma & Healthcare Monitor Worldwide

Allogene Therapeutics R&D Showcase Features Hematologic and Solid Tumor Advances Across its AlloCAR T™ Platform


Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T) products for cancer, today hosted an R&D Showcase providing an extensive overview of pipeline advances from three clinical stage AlloCAR T programs. The event also included panel discussions with leading experts on the potential for these programs to substantially improve patient care and access if approved. Clinical updates on the Companys hematologic franchises focused on investigational products targeting CD19 and BCMA for the treatment of large B cell lymphoma (LBCL) and multiple myeloma (MM), respectively. The solid tumor presentation provided the first look at initial clinical data on ALLO-316, an AlloCAR T product candidate targeting CD70 for the treatment of clear cell renal cell carcinoma (RCC).

The Company also unveiled its Dagger technology, the Companys next generation allogeneic platform technology designed to prevent immune rejection and enable a window of persistence during which AlloCAR T cells can expand and actively target and destroy cancer cells. Dagger has the potential to enable a pipeline of innovative product candidates.

"From the very beginning, one of the biggest questions facing the field of allogeneic CAR T has been whether an off-the-shelf product can match the high durability bar set by autologous therapies. We believe the longer-term follow up data from our Phase 1 studies establish that this is indeed possible," said David Chang, M.D., Ph.D., President, Chief Executive Officer and Co-Founder of Allogene. "As we look to confirm our exciting results in the first allogeneic CAR T Phase 2 trial for which we are enrolling, I believe we are entering a new phase of development for AlloCAR T, one in which the field can turn its attention to when and not if these product candidates will begin to provide great benefit to patients with cancer.

We have undertaken a rigorous step-by-step process to evaluate, understand and optimize our AlloCAR T platform. Our continuous learning approach has enabled an industry-leading pipeline of off-the-shelf AlloCAR T product candidates for hematologic and solid tumor malignancies, and we are delighted to be sharing some initial, highly promising data in solid tumors, said Rafael Amado M.D., Executive Vice President of Research and Development at Allogene. Our focus is to advance this pipeline, including the execution of our Phase 2 trial for ALLO-501A and preparation for a potential Phase 2 trial on ALLO-715. We believe success in this endeavor will enable us to bring the promise of cell therapy to far more patients in need.

CD19 Program: ALPHA Studies

The Company conducted an extensive Phase 1 program designed to evaluate and optimize all aspects of its lead product candidate, including the dose and schedule of ALLO-501A and ALLO-647. In addition, following a review of the Phase 1 program, the Company determined that its AlloyTM manufacturing process was associated with robust performance. Alloy is being deployed in the ongoing Phase 2 ALPHA2 trial.

A single infusion of CAR+ cells with FCA90 lymphodepletion regimen consisting of fludarabine (30 mg/m2/day x 3 days) and cyclophosphamide (300 mg/m2/day x 3 days) (standard flu/cy) plus 90 mg of ALLO-647 (Single Dose FCA90) was deemed preferrable to two infusions of CAR+ cells (Consolidation Regimen). In the Consolidation Regimen, ALLO-647 dosing was split into 60 mg and 30 mg prior to the first and second infusion of CAR+ cells. This finding underscores the importance of optimizing lymphodepletion in allogeneic cell therapy.

Data from the Phase 1 trials of ALLO-501 and ALLO-501A support the ability of a single administration of CAR T cells to generate deep and durable responses similar to approved autologous CAR T therapies. As of the October 25, 2022 data cutoff, 33 autologous CAR T nave patients with relapsed/refractory (r/r) LBCL were treated with Alloy process material. Ninety-two percent (92%) of all enrolled patients received investigational product with 100% of infused product manufactured and released as per product specifications. Patients were able to initiate treatment within two days of enrollment.

Responses in the ALPHA trials were overall durable. Of the nine patients treated with Alloy process material who achieved a complete response (CR) at six months, eight remain in remission with the longest complete response ongoing at 26+ months.

Among 12 patients treated with the Single Dose FCA90 regimen, the overall response rate (ORR) was 67% and 58% achieved CRs. Among the eight patients in the Single Dose FCA90 cohort who had the opportunity to be followed for six months or more, four (50%) were in CR at both six and 12 months. Alloy Process


(n = 48)All Alloy

(n=33)Consolidation Regimen

(n=15)Single Dose FCA90


Overall Response Rate (ORR), n (%)

23 (48)19 (58)8 (53)8 (67)

Complete Response (CR), n (%)

14 (29)14 (42)6 (40)7 (58)

6 Month CR Rate, n (%)9 (23)9 (31)5 (33)4 (50)

12 Month CR Rate, n (%)8 (21)8 (28)4 (27)4 (50)

The ALPHA Phase 1 trials demonstrated a manageable safety profile. There were no observed dose limiting toxicities (DLTs) or graft-vs-host disease (GvHD). Among patients treated with Single Dose FCA90, there was no Grade 3+ cytokine release syndrome (CRS) or neurotoxicity. One patient (8%) experienced a Grade 3+ infection and two (17%) experienced prolonged Grade 3+ cytopenia. As previously reported, one Grade 5 event occurred. No new Grade 5 events have occurred. Alloy Process


(n=48)All Alloy

(n=33)Consolidation Regimens

(n=15)Single Dose


Adverse Events

of InterestAll Grs

n (%)Gr 3+

n (%)All Grs

n (%)Gr 3+

n (%)All Grs

n (%)Gr 3+

n (%)All Grs

n (%)Gr 3+

n (%)

CRS11 (23)08 (24)03 (20)04 (33)0

Neurotoxicity15 (31)3 (6)12 (36)2 (6)6 (40)2 (13)4 (33)0



Infection25 (52)9 (19)19 (58)5 (15)8 (53)3 (20)8 (67)1 (8)

Prolonged Gr3+ cytopenia-9 (19)-4 (12)-2 (13)-2 (17)

The Company has initiated the industrys first potentially pivotal Phase 2 allogeneic CAR T clinical trial (ALPHA2 trial) with ALLO-501A in patients with r/r LBCL. The single-arm trial will utilize a single dose of ALLO-501A (120 million CAR+ cells) with the FCA90 lymphodepletion regimen. The ALPHA2 trial will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy. The primary endpoint of this trial is ORR, and the key secondary endpoint is duration of response (DoR).


The Phase 1 UNIVERSAL study is a dose escalation trial in patients with heavily pretreated r/r multiple myeloma (MM). Dose expansion cohorts comprised of a single dose of ALLO-715 (320 million CAR+ cells) and either FCA39 lymphodepletion (standard flu/cy plus 39 mg of ALLO-647) or FCA60 lymphodepletion (standard flu/cy plus 60 mg of ALLO-647) demonstrated substantial and durable responses. Importantly, 92% of all enrolled patients received investigational product with 100% of infused product manufactured and released as per product specifications. Patients were able to initiate treatment within five days of enrollment and no bridging therapy was required.

Through a median follow-up of 14.8 months as of the October 11, 2022 data cutoff, the ORR was 67% in the FCA60 cohort and the very good partial response or better rate (VGPR+) was 42%. All VGPR+ were minimal residual disease (MRD) negative. The median duration of response was 9.2 months, with the longest ongoing response at 24 months. Expansion Cohorts

LD RegimenTotal




ORR*, n (%)15 (65)7 (64)8 (67)

VGPR+ rate, n (%)11(48)6 (54)5 (42)

CR/sCR rate, n (%)5 (22)3 (27)2 (17)

Median DOR8.38.39.2

* Five patients with best responses ranging from stable disease to partial response are not included due to limited follow-up.

Safety profile was manageable with low-grade and reversible neurotoxicity and no GvHD. In the expansion cohorts, there was low use of tocilizumab (32%) and steroids (25%). Eight patients (29%) experienced Grade 3+ infections and prolonged Grade 3+ cytopenias. As previously reported, one Grade 5 event occurred in the expansion cohorts and no new Grade 5 events have occurred. Expansion Cohorts


Adverse Events

of InterestAll Grades

n (%)Grade 3+

n (%)

CRS19 (68)1 (4)

Neurotoxicity17 (61)0

ICANS1 (4)0


Infection19 (68)8 (29)

Prolonged Gr3+ Cytopenia-8 (29)

The Company is planning a potentially pivotal Phase 2 trial for ALLO-715 in r/r MM, including planned regulatory discussions, optimizing the manufacturing process and transitioning manufacturing of ALLO-715 to the Companys own manufacturing facility, Cell Forge 1.

As part of the Companys BCMA strategy, the Company has also been conducting a Phase 1 clinical trial (the IGNITE trial) of ALLO-605, the first product candidate to incorporate TurboCAR technology. TurboCAR technology allows cytokine signaling to be engineered selectively into CAR T cells and has shown the ability to improve the potency and persistence of the cells and to delay exhaustion of the cells in preclinical models. The Company is currently reviewing the manufacturing process for ALLO-605 and is not enrolling patients in the IGNITE trial at this time.

CD70 Program: TRAVERSE Study

ALLO-316, the Companys first AlloCAR T candidate for solid tumors, targets CD70, an antigen expressed on clear cell renal cell carcinoma (RCC) and other malignancies. The ongoing Phase 1 TRAVERSE study is enrolling patients with advanced or metastatic RCC who have progressed on or intolerant to standard therapies, including an immune


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