Allogene Therapeutics Announces Oral Presentation of Initial Results from its Phase 1 Dose Escalation Study of ALLO-715 in Relapsed/Refractory Multiple Myeloma at the 62nd Annual Meeting of the American Society of Hematology
- Category: DNA RNA and Cells
- Published on Thursday, 05 November 2020 12:02
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- ALLO-715, an Allogeneic BCMA CAR T Therapy Dosed with an ALLO-647 Based Lymphodepletion Regimen, Reported No Neurotoxicity or GvHD Across Three Cell Doses (40M, 120M, and 320M CAR+ cells) and Lower Dose (39mg) ALLO-647
- Dose Dependent Activity Was Observed with 320M Cell Dose of ALLO-715 (DL3) Associated with a 60% Overall Response Rate (ORR)
- All DL3 Patients with a VGPR or Greater Achieved MRD Negative Status
- Results from Additional Patients, Including Patients Treated at Higher Doses of ALLO-715 and ALLO-647 Will Be Presented on December 5, 2020
- Study Continues Enrollment to Optimize Dosing and Lymphodepletion
- Preclinical Data Will Also be Presented on ALLO-605, a BCMA TurboCAR T™ Cell Therapy and ALLO-316 Targeting CD70 in Acute Myeloid Leukemia
SOUTH SAN FRANCISCO, CA, USA I Novembere 04, 2020 I Allogene Therapeutics, Inc. (Nasdaq: ALLO), a clinical-stage biotechnology company pioneering the development of allogeneic CAR T (AlloCAR T™) therapies for cancer, today announced that it will present initial data from its Phase 1 UNIVERSAL trial of ALLO-715, an anti-BCMA AlloCAR T therapy, in relapsed/refractory multiple myeloma in an oral presentation at the 62nd Annual Meeting of the American Society of Hematology (ASH), taking place virtually December 5 – 8, 2020. Preclinical findings from investigations of ALLO-316, an AlloCAR T targeting CD70 in acute myeloid leukemia and ALLO-605, a BCMA-directed TurboCAR TTM cell therapy in multiple myeloma, will also be presented in poster sessions.
“We’re looking forward to presenting initial clinical data for our first anti-BCMA AlloCAR T therapy, ALLO-715, which we believe will provide insights into how we might optimize lymphodepletion and cell dose to reach its potential for patients in need of readily available treatments options,” said Rafael Amado, M.D., Executive Vice President of Research & Development and Chief Medical Officer of Allogene. “These findings will help inform trial design for our BCMA platform as we look to advance ALLO-715, alone and in combination with a gamma secretase inhibitor, as well as ALLO-605, our first TurboCAR T clinical candidate.”
In the initial dose escalation phase of the UNIVERSAL trial, patients received lymphodepletion (LD) followed by ALLO-715 at one of three dose levels (DL) in a 3+3 dose escalation design. At the time of the July 2020 abstract data cutoff, two LD regimens were being evaluated:
- FCA: Fludarabine 90 mg/m2, Cyclophosphamide 900 mg/m2, and ALLO-647 39 mg divided over three days; and
- CA: Cyclophosphamide 900 mg/m2 and ALLO-647 39 mg divided over three days.
The ASH abstract includes preliminary data on the first 15 patients evaluable for efficacy and treated with escalating doses of ALLO-715 as well as lower dose (39mg) ALLO-647. Patients were in advanced stage of disease with a median of five prior lines of therapy. The trial did not permit bridging therapy.
In 15 evaluable patients, higher dose of ALLO-715 (DL3) achieved greater activity with 60% (3/5) patients responding (95% CI 14.7, 94.7). Of the three patients who received DL3 FCA, two responded (1 stringent complete response (sCR) and 1 very good partial response (VGPR)) and both were minimum residual disease (MRD) negative by local MRD testing.
|LD Regimen and
40 x 106
160 x 106
320 x 106
160 x 106
320 x 106
|ORR, n (%)||0 (0%)||2 (50%)||2 (66%)||0 (0%)||1(50%)||3/5 (60%)
At the time of the data cutoff, 17 of the patients were evaluable for safety. No neurotoxicity or graft-vs-host disease (GvHD) was observed. Cytokine release syndrome (CRS) was reported in four patients (24%) with three Grade 1 and one Grade 2. All CRS was resolved without tocilizumab or corticosteroids. The most common Grade ≥ 3 adverse events were anemia (41.2%), neutropenia (41.2%), lymphopenia (29.4%), and thrombocytopenia (29.4%).
Four (23.5%) instances of Grade ≥ 3 infections were observed. Three of these were Grade 3 and resolved with treatment. The fourth was a Grade 5 event of suspected fungal pneumonia that occurred on day eight post-ALLO-715 infusion. The suspected fungal pneumonia was diagnosed on the day after cell infusion in this patient with advanced and rapidly progressing disease who had failed multiple lines of therapy. This event occurred in the CA cohort, and it was assessed by the investigator as related to progressive disease and the CA conditioning.
The oral presentation will include data on approximately 20 patients evaluable for efficacy across ALLO-715 cell dose cohorts and lower dose (39mg) of ALLO-647, as well as patients evaluable for efficacy who were treated with a higher dose of ALLO-715 and higher doses of ALLO-647. The Phase 1 UNIVERSAL study continues to enroll patients at these higher doses in an effort to optimize the therapy.
The ASH abstracts are now available at www.hematology.org. Allogene will also host a conference call on December 5th following the virtual presentation. Details on the ASH presentations are as follows:
Allogene Oral Presentation
Session: 653. Myeloma/Amyloidosis: Therapy, Excluding Transplantation; CAR T Therapies for Myeloma: Novel Approaches and Longer-Term Follow Up Data
Title: Universal: An Allogeneic First-in-Human Study of the Anti-BCMA ALLO-715 and the Anti-CD52 ALLO-647 in Relapsed/Refractory Multiple Myeloma
Presenter: Sham Mailankody, M.D., Memorial Sloan Kettering Cancer Center
Session Date & Time: Saturday, December 5, 2020; 9:30 a.m. - 11 a.m. PT
Allogene Poster Presentations
Session: 616. Acute Myeloid Leukemia: Novel Therapy, Excluding Transplantation: Poster II
Title: Investigation of ALLO-316: A Fratricide-Resistant Allogeneic CAR T Targeting CD70 As a Potential Therapy for the Treatment of AML
Presenter: Nguyen Tan, Allogene Therapeutics
Session Date & Time: Sunday, December 6, 2020; 7 a.m. - 3:30 p.m. PT
Session: 703. Adoptive Immunotherapy: Mechanisms and New Approaches: Poster III
Title: Preclinical Evaluation of ALLO-605, an Allogeneic BCMA TurboCAR TTM Cell Therapy for the Treatment of Multiple Myeloma
Presenter: Cesar Sommer, Ph.D., Allogene Therapeutics
Session Date & Time: Monday, December 7, 2020; 7 a.m. - 3 p.m. PT
About Allogene Therapeutics
Allogene 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.
SOURCE: Allogene Therapeutics