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2019 Universal Updated Phase 1 Data Highlights Role of Allogeneic Anti-BCMA ALLO-715 Therapy for Relapsed/Refractory Multiple Myeloma

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster I
Hematology Disease Topics & Pathways:
Biological therapies, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Therapies
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Sham Mailankody, MBBS 1, Jeffrey V. Matous, MD2, Michaela Liedtke, MD3, Surbhi Sidana, MD4, Olalekan O. Oluwole, MBBS5, Meera Mohan, MD, MS6*, Jose C. Cruz, MD7, Rajneesh Nath, MD8, Faiz Anwer, MD9*, Adriana Rossi, MD, MSc10, Myo Htut, MD11, Shahbaz A. Malik, MD12, Srinivas Ghatta, PhD13*, Myles Dillon, PhD13*, Wendy Ying, PhD13*, Lynn Navale, MS13*, Erin E. Karski, MD13*, Arun Balakumaran, MD13 and Shaji K Kumar, MD14

1Memorial Sloan Kettering Cancer Center, New York, NY
2Colorado Blood Cancer Institute, Denver, CO
3Department of Medicine, Divisions of Oncology and Hematology, Stanford University, Stanford, CA
4Division of Blood and Marrow Transplantation and Cellular Therapy, Department of Medicine, Stanford University School of Medicine, Stanford, CA
5Vanderbilt University Medical Center, Nashville, TN
6Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI
7Texas Transplant Institute, San Antonio, TX
8Banner MD Anderson Cancer Center, Scottsdale, AZ
9Department of Hematology and Medical Oncology, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH
10Icahn School of Medicine, Mount Sinai Hospital, New York, NY
11Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, CA
12St. David's South Austin Medical Center, Austin, TX
13Allogene Therapeutics, South San Francisco, CA
14Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN

Background

Autologous chimeric antigen receptor (CAR) Ts have advanced the treatment of relapsed/refractory multiple myeloma. Due to access and treatment delays, many patients (pts) may not benefit from these therapies. Allogeneic CAR T cell products may address access challenges and ensure eligible pts benefit. ALLO-715 is a genetically modified anti–B cell maturation antigen (BCMA) AlloCAR T™ cell therapy, which uses Cellectis technology to disrupt the T-cell receptor alpha constant (TRAC) and the CD52 genes to eliminate the risk of graft-versus-host disease (GvHD) and permit the use of ALLO-647, an anti-CD52 monoclonal antibody (mAb), for selective and transitory host lymphodepletion (LD).

Methods

UNIVERSAL is an open-label, Phase 1 trial (NCT04093596) in adults with relapsed/refractory (R/R) multiple myeloma who have received ≥3 prior lines of therapy including a proteasome inhibitor, immunomodulator, and anti-CD38 mAb. Pts must be refractory to their last treatment line. Part A evaluates the safety, efficacy, cellular kinetics, immunogenicity, and pharmacodynamics of a single dose of ALLO-715 following lymphodepletion with an ALLO-647 containing regimen. Pts receive LD followed by ALLO-715 at 1 of 4 dose levels (DLs) in a 3+3 dose escalation design: 40 (DL1), 160 (DL2), 320 (DL3), and 480 (DL4) x 106 CAR+ T cells with varying doses and schedules of LD including ALLO-647 with fludarabine and cyclophosphamide (FC). After the completion of cell dose and LD exploration, two DL3 cohorts were chosen for expansion using lymphodepletion of FC and ALLO-647 (A) at 39mg or 60mg. This publication provides updated safety data on the overall Part A study population and highlights efficacy data from the two expanded DL3 cohorts.

Results

As of June 22, 2022, 53 pts were enrolled; 98% of pts receiving LD were treated with ALLO-715 with one remaining patient (2%) pending ALLO-715 infusion at the time of the data cut-off. Median time from enrollment to LD was 5 days and no pts required bridging therapy. One hundred percent of pts received product manufactured and released per product specifications. Pts were pretreated with a range of 3 to 11 (median:5) prior lines of therapy; 44% were penta refractory. Twenty-three% of pts were international staging system (ISS) Stage III, 42% had high risk cytogenetics, and 19% had extramedullary disease. No GvHD or dose-limiting toxicities were observed. Grade (Gr) 3+ adverse events (AEs) included neutropenia, anemia, thrombocytopenia, and lymphopenia. Cytokine release syndrome (CRS) occurred in 52%, all Gr 1/2 except 1 pt with Gr 3. The use of tocilizumab and steroids across all pts was 19% and 15%, respectively. Potential events of neurotoxicity were identified in 5 (11%) pts, all Gr 1/2. Infections occurred in 56% of pts, with Gr 3+ in 29% of pts. Of all infections, viral infections or low Gr viral reactivation, were most common. No new Gr 5 events occurred.

Early results were presented previously (ASH 2021) and this efficacy analysis focuses on pts treated at DL3, which was considered the most active cell dose, using FCA39 (n=11) and FCA60 (n=10) (Table). In these cohorts, the overall response rates (ORR) were 64% and 80%, for FCA39 and FCA60, respectively, with 55% and 50% achieving very good partial response or better (VGPR+) and 27% and 20% achieving complete response/stringent complete response (CR/sCR). Responses were observed at the first disease assessment (14 days) in 9/15 responders. With median follow-up times of 12.1 months in the FCA39 cohort and 16.8 months in the FCA60 cohort, 2 pts are in ongoing response at 12 months in the FCA39 cohort and 3 pts at 12, 19, and 20 months in the FCA60 cohort. Of 11 pts in these cohorts with VGPR+ assessed for minimum residual disease (MRD), 10 (91%) were MRD negative. Safety of these regimens was similar to the overall safety.

Conclusions

UNIVERSAL demonstrates significant and durable responses from allogeneic CAR T therapy. ALLO-715 DL3 with FCA39 and FCA60 was associated with clinically meaningful efficacy, including VGPR+ rates of 55% and 50% without requiring leukapheresis or bridging therapy. Ninety-eight percent of pts receiving LD received ALLO-715 with 100% of product manufactured and released per product specifications. FCA induces a deep and durable window of lymphocyte depletion allowing CAR T cell expansion. The UNIVERSAL trial continues to enroll pts in the FCA60 cohort and updated data will be presented.

Disclosures: Mailankody: Evicore: Consultancy; Janssen Oncology: Consultancy, Research Funding; BioAscend: Consultancy; Optum Oncology: Consultancy; Allogene Therapeutics: Research Funding; Takeda Oncology: Research Funding; Juno Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding; Fate Therapeutics: Research Funding; Plexus Communication: Honoraria; OncLive: Honoraria; Physician Education Resource: Honoraria; Legend Biotech: Consultancy; Memorial Sloan Kettering Cancer Center: Current Employment. Matous: BeiGene: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees. Liedtke: Seagen Inc.: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Natera: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; Allogene: Research Funding; Alnylam: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Caelum: Research Funding; Gilead: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees. Sidana: Bristol Myers Squibb: Consultancy, Research Funding; Sanofi: Consultancy; Janssen: Consultancy, Research Funding; Allogene: Research Funding; Oncopeptides: Consultancy; Prothena: Honoraria; Magenta Therapeutics: Consultancy, Research Funding. Oluwole: Kite, a Gilead Company: Research Funding; Pfizer: Consultancy; TG Therapeutics: Consultancy; Curio Science: Consultancy; ADC Therapeutics: Consultancy; Nektar: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Syncopation: Consultancy; Epizyme: Consultancy. Nath: Actinium: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria. Rossi: adaptive: Consultancy; janssen: Consultancy; gsk: Consultancy; BMS: Consultancy; sanofi: Consultancy. Ghatta: Allogene Therapeutics: Current Employment. Dillon: Allogene Therapeutics: Current Employment. Navale: Allogene, Gamida Cell, Neogene: Consultancy, Current Employment, Current equity holder in private company, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Karski: Crisper Therapeutics: Other: Equity Ownership; Allogene Therapeutics: Current Employment; Nektar Therapeutics: Other: Equity Ownership. Kumar: Roche: Research Funding; Novartis,: Research Funding; Merck,: Research Funding; MedImmune/Astra Zeneca,: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE,: Research Funding; Adaptive,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie,: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Research Funding; Oncopeptides: Other: Independent review committee.

*signifies non-member of ASH