ALLO-647 / Allogene Overland Biopharm - LARVOL DELTA

Allogeneic CAR T Cell Products Cemacabtagene Ansegedleucel/ALLO-501 in Relapsed/Refractory Large B-Cell Lymphoma: Phase 1 Experience From the ALPHA2/ALPHA Clinical Studies. (PubMed, J Clin Oncol) - "Allogeneic CD19 CAR T cells demonstrated promising overall and durable complete response rates with a manageable safety profile in CD19 CAR T-naive patients with R/R LBCL, supporting additional evaluation of cema-cel in patients with LBCL."

Journal • P1 data • B Cell Lymphoma • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ALPHA-2: Safety and Efficacy of ALLO-501A Anti-CD19 Allogeneic CAR T Cells in Adults with Relapsed/Refractory Large B Cell Lymphoma, Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (ALPHA2) (clinicaltrials.gov) - P1/2 | N=160 | Active, not recruiting | Sponsor: Allogene Therapeutics | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jan 2025 ➔ Aug 2025

Enrollment closed • Trial primary completion date • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma

ALPHA3, a Pivotal Phase 2 Study of First-Line Consolidation with Cemacabtagene Ansegedleucel (Cema-Cel) in Patients with Large B-Cell Lymphoma and Minimal Residual Disease after Response to Standard Therapy (ASH 2024) - P2 | "Introduction : R-CHOP is expected to cure approximately 60% of patients with large B-cell lymphoma (LBCL) as first-line (1L) therapy...In Part A, patients will be randomized to the standard-of-care observation arm or to 1 of 2 treatment arms (cema-cel [120×106 CAR T cells] following a 3-day lymphodepletion regimen with fludarabine [30 mg/m2/day] and cyclophosphamide [300 mg/m2/day] administered with or without the anti-CD52 monoclonal antibody, ALLO-647 [30 mg/day])...Site activation is ongoing, and sites outside the United States are being considered. The study was initiated in June 2024 and plans to accrue into 2026."

Clinical • Minimal residual disease • P2 data • Residual disease • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Epstein-Barr Virus Infections • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Mediastinal B Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • IRF4

ALLO-316 in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC): updated safety and efficacy from the phase 1 TRAVERSE multicenter study (SITC 2024) - P1 | "Escalating doses of ALLO-316 (40–240 × 106 allogeneic CAR+ T cells) were administered intravenously on Day 0 after lymphodepletion with fludarabine and cyclophosphamide +/- ALLO-647, an anti-CD52 monoclonal antibody...Immune effector cell-associated HLH-like syndrome (IEC-HS) was observed in a subset of patients and will be presented along with its management with ruxolitinib...Preliminary analyses in patients with tumors expressing CD70 provided encouraging evidence of CAR activity. These findings support further evaluation of ALLO-316 in CD70+ ccRCC and other CD70+ malignancies."

Clinical • Metastases • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • CD70

TRAVERSE: Updated safety and efficacy of ALLO-316 in advanced/metastatic clear cell renal cell carcinoma (ccRCC) (IKCS 2024) - P1 | "Escalating doses of ALLO-316 (40 to 240×10^6 allogeneic CAR+ T cells) were administered intravenously after lymphodepletion (fludarabine and cyclophosphamide +/- ALLO-647, an anti-CD52 monoclonal antibody)...A subset of patients experienced immune effector cell-associated HLH-like syndrome (IEC-HS); these IEC-HS data and management with ruxolitinib will be presented...Single-dose ALLO-316 demonstrated a manageable safety profile in relapsed/ refractory advanced/metastatic ccRCC. Preliminary analyses in CD70+ tumors provided encouraging evidence of CAR activity, supporting further evaluation of ALLO-316 in CD70+ ccRCC and other"

Clinical • Metastases • Anemia • Clear Cell Renal Cell Carcinoma • Fatigue • Genito-urinary Cancer • Graft versus Host Disease • Hematological Disorders • Immunology • Leukopenia • Neutropenia • Oncology • Renal Cell Carcinoma • Solid Tumor • CD70

ALPHA3: A Pivotal Phase 2 Study Evaluating the Safety and Efficacy of First-Line (1L) Consolidation With Cemacabtagene Ansegedleucel (Cema-Cel) in Patients With Large B-Cell Lymphoma (LBCL) and Minimal Residual Disease (MRD) After Response to Standard Therapy (SOHO 2024) - "Context: First-line therapy outcomes for patients with LBCL are favorable with R-CHOP (~60% cure rate; Spinner, Oncology 2022)...Treatment includes cema-cel (120×106 CAR T cells) following a 3-day lymphodepletion regimen with fludarabine (30 mg/m2/day) and cyclophosphamide (300 mg/m2/day) administered with/without the anti-CD52 monoclonal antibody ALLO-647 (30 mg/day)...Main Outcome Measures: Primary endpoint is event-free survival per independent review committee (IRC), with hierarchical testing of key secondary endpoints of progression-free survival per IRC and overall survival. Secondary endpoints include MRD clearance and safety (cema-cel and ALLO-647)."

Clinical • Minimal residual disease • P2 data • Residual disease • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ALPHA2: A Phase 1b Study Evaluating the CD19 Allogeneic CAR T Cell Product Cemacabtagene Ansegedleucel (Cema-Cel) in Patients With Relapsed/ Refractory (R/R) Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) (SOHO 2024) - P1/2 | "Interventions: Participants will undergo a 3-day lymphodepletion regimen consisting of fludarabine 30 mg/ m 2/day, cyclophosphamide 300 mg/m2/day, and ALLO-647 30 mg/ day followed by cema-cel infusion at a dose of 120×106 CAR+ cells. Main Outcome Measures: The primary endpoint is safety. Secondary endpoints include overall response rate, duration of response, time to response, and progression-free survival per investigator assessment."

CAR T-Cell Therapy • Clinical • P1 data • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Leukemia • Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma • BCL2 • TP53

Safety and Efficacy of ALLO-605 an Anti-BCMA Allogeneic CAR T Cell Therapy in Patients With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=6 | Terminated | Sponsor: Allogene Therapeutics | N=136 ➔ 6 | Trial completion date: Jul 2025 ➔ Oct 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jul 2025 ➔ Oct 2023; Terminated (Halted Prematurely)

CAR T-Cell Therapy • Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

ALPHA3: Consolidation of First-Line MRD+ Remission With Cema-cel in Patients With LBCL (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: Allogene Therapeutics

New P2 trial • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

EXPAND: Evaluation of Lymphodepletion With ALLO-647 in Adults With R/R Large B Cell Lymphoma Receiving ALLO-501A Allogeneic CAR T Cell Therapy (clinicaltrials.gov) - P2 | N=70 | Active, not recruiting | Sponsor: Allogene Therapeutics | Recruiting ➔ Active, not recruiting | Trial primary completion date: Apr 2025 ➔ Feb 2024

CAR T-Cell Therapy • Enrollment closed • Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Innovative perspectives in renal carcinoma therapy: exploring the therapeutic potential of Car-T cells directed to the CD70 and Allo 316. (ICUC 2024) - "Car-T immunotherapy, aiming at the CD70 in tumor cells, brings hope in the treatment of advanced renal cell carcinoma.Traversse study highlights the efficacy of Allo-316, with a high rate of disease control.However, side effects such as neurotoxicity and cytokine release syndrome require careful monitoring.These results represent advances in the search for safer and more effective treatments for patients with advanced kidney cancer."

CAR T-Cell Therapy • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Infectious Disease • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • CD20 • CD52 • CD70

Allogene Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Business Update (GlobeNewswire) - "ALPHA3 will randomize approximately 230 patients who are in clinical remission but remain MRD positive at the end of standard 1L chemoimmunotherapy to either consolidation with cema-cel or the current standard of care, observation, which means to 'watch and wait' for the disease to relapse. The primary endpoint of the ALPHA3 trial is event free survival (EFS). The trial will initially test two lymphodepletion regimens (one with standard fludarabine and cyclophosphamide plus ALLO-647 and one without ALLO-647). One lymphodepletion arm will be discontinued following a planned interim analysis in mid-2025 designed to select the most appropriate regimen for this patient population. Start-up activities for the ALPHA3 trial are underway and the trial is expected to begin in mid-2024."

New P2 trial • Diffuse Large B Cell Lymphoma

Allogene Therapeutics Announces 2024 Platform Vision to Redefine the Future of CAR T Led by ALPHA3, the Industry's First Pivotal Trial for Frontline Consolidation in Large B-Cell Lymphoma (GlobeNewswire) - "The new Phase 1 ALPHA2 cohort of 12 patients treated with the investigational product cema-cel provides the opportunity to set a higher bar where patients with CLL are not reliant on their own T cells’ fitness to benefit from the curative potential of CAR T. This study, driven by investigator enthusiasm, will leverage currently active ALPHA2 trial sites in the U.S. which should allow it to advance quickly. It is expected to begin enrolling in Q1 2024 with initial data projected by YE 2024."

P1/2 data • Trial status • Diffuse Large B Cell Lymphoma

Allogene Therapeutics Announces 2024 Platform Vision to Redefine the Future of CAR T Led by ALPHA3, the Industry's First Pivotal Trial for Frontline Consolidation in Large B-Cell Lymphoma (GlobeNewswire) - "Start-up activities for the ALPHA3 trial have been initiated. The study will randomize approximately 230 patients who are MRD positive at the end of 1L therapy to either consolidation with cema-cel or the current standard of care (observation). The design, with a primary endpoint of event free survival (EFS), will initially include two lymphodepletion arms (one with standard fludarabine and cyclophosphamide plus ALLO-647 and one without ALLO-647)...the Company will focus on quickly advancing this market-defining ALPHA3 trial and deprioritize the currently enrolling third line (3L) ALPHA2 and EXPAND trials."

Clinical protocol • Enrollment status • Diffuse Large B Cell Lymphoma

ALLO-647 for Lymphodepletion in the Allogeneic CAR T Setting: Safety Experience with ALLO-501/501A in Patients (Pts) with Relapsed/Refractory (r/r) Large B-Cell and Follicular Lymphomas (ASH 2023) - P1, P1/2 | "Updated phase 1 data for ALLO-501 (ALPHA; NCT03939026) and ALLO-501A (ALPHA2; NCT04416984) showed that administration of anti-CD19 allogeneic CAR T product following use of lymphodepletion that includes ALLO-647 plus fludarabine and cyclophosphamide provided durable responses and an acceptable safety profile in CAR T-cell–naive pts with r/r large B-cell lymphoma (LBCL; Locke FL, et al. These data suggest allogeneic CAR T-cell products administered following lymphodepletion consisting of FC and ALLO-647 can provide a safe and tolerable alternative to autologous CAR T-cell therapy."

Clinical • Anemia • CNS Disorders • Cytomegalovirus Infection • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • Pneumonia • Rare Diseases • Respiratory Diseases • Thrombocytopenia

Allogene Therapeutics Presents Comprehensive Safety Data of Proprietary Lymphodepletion Agent ALLO-647 at the 65th Annual Meeting of the American Society of Hematology (GlobeNewswire) - "Allogene Therapeutics, Inc...today announced the presentation of data from a comprehensive safety review of patients treated in the Phase 1 ALPHA/ALPHA2 trials with ALLO-501/501A at the 65th Annual Meeting of the American Society of Hematology (ASH) in San Diego, CA....The safety review, which encompasses all 87 Phase 1 patients treated in both relapsed/refractory (r/r) Large B Cell Lymphoma (LBCL) and follicular lymphoma (FL), demonstrates that investigational ALLO-647 added to standard lymphodepletion can safely provide a window for the expansion and persistence of AlloCAR T cells, and has the potential to induce deep and durable remissions in relapsed and treatment-refractory cancers....The addition of ALLO-647 to standard lymphodepletion did not result in adverse events beyond those commonly observed with autologous CAR T cell therapy."

Retrospective data • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

DURABLES RESPONSES ACHIEVED WITH ANTI-CD19 ALLOGENEIC CAR T ALLO-501/501A IN PHASE 1 TRIALS OF AUTOLOGOUS CAR T-NAÏVE PATIENTS WITH RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (R/R LBCL) (EHA 2023) - P1, P1/2 | "Conditioning with a regimen of fludarabine (F)/cyclophosphamide (C)/ALLO-647 (A, a humanized anti-CD52 monoclonal IgG1) targets host CD52+ immune cells for elimination while allowing subsequently infused CD52-knock-out ALLO-501/501A cells to persist. A single dose of AlloCAR T therapy following FCA90 conditioning provided durable responses with a manageablesafety profile in autologous CAR T-naïve pts with r/r LBCL. Among 8 pts who received FCA90 and ALLO-501/501A and had the opportunity to be evaluated for 6 months, 50% maintained that response for at least 6 months, with a median DOR of 23.1 months. These findings support broader evaluation of ALLO-501A/ALLO-647 in the ongoing, first potentially pivotal phase 2 trial (ALPHA2) of AlloCAR T therapy."

Clinical • P1 data • Diffuse Large B Cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 1 results with anti-CD19 allogeneic CAR T ALLO-501/501A in relapsed/refractory large B-cell lymphoma (r/r LBCL). (ASCO 2023) - P1, P1/2 | " In these two multicenter, single-arm, open-label, phase 1 trials, a cohort of autologous CAR T-naïve pts with r/r LBCL underwent 3-day lymphodepletion (LD) with FCA90, fludarabine (F, 30 mg/m2/day), cyclophosphamide (C, 300 mg/m2/day), and ALLO-647 (A [anti-CD 52 mAb] 30 mg/day; total dose: 90 mg) followed by a single dose of ALLO-501 or ALLO-501A produced by the Alloy manufacturing process. A one-time dose of allogeneic CAR T therapy following LD with FCA90 provided durable responses with a manageable safety profile in patients with r/r/ LBCL comparable to those treated with autologous CAR T cells. This treatment enables rapid access to off-the-shelf treatment with a median time from trial enrollment to treatment of 3 days. These findings support broader evaluation of ALLO-501A in the ongoing, first potentially pivotal phase 2 trial (ALPHA2) of off-the-shelf allogeneic CAR T cells."

P1 data • Diffuse Large B Cell Lymphoma • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Allogene Therapeutics Reports Third Quarter 2023 Financial Results and Business Update (GlobeNewswire) - "The Phase 1 dose escalation TRAVERSE trial in patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed on standard therapies including an immune checkpoint inhibitor and a VEGF-targeting therapy is ongoing. Dose escalation in the TRAVERSE trial is expected to be completed by early 2024. The Company intends to target an academic forum in early 2024 to provide an update from this trial."

P1 data • Trial status • Renal Cell Carcinoma

Allogene Therapeutics Announces Poster Presentations at the 65th Annual Meeting of the American Society of Hematology (GlobeNewswire) - "The first poster is a comprehensive safety review of all 85 patients treated in the Phase 1 ALPHA/ALPHA2 studies in relapsed/refractory (r/r) Large B Cell Lymphoma (LBCL) and follicular lymphoma (FL) to characterize the overall safety profile when ALLO-647 is added to standard lymphodepletion....The second poster showcases translational results from ALPHA2 generated through a collaboration with researchers from The University of Texas MD Anderson Cancer Center."

P1 data • Review • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

TRAVERSE: Safety and Efficacy of ALLO-316 in Subjects With Advanced or Metastatic Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P1 | N=120 | Recruiting | Sponsor: Allogene Therapeutics | Trial primary completion date: Dec 2022 ➔ Aug 2025

Metastases • Trial primary completion date • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL) (clinicaltrials.gov) - P1 | N=132 | Active, not recruiting | Sponsor: Allogene Therapeutics | Trial completion date: Dec 2027 ➔ Sep 2027 | Trial primary completion date: Dec 2022 ➔ Sep 2027 | Recruiting ➔ Active, not recruiting

CAR T-Cell Therapy • Enrollment closed • IO biomarker • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Safety and Efficacy of ALLO-605 an Anti-BCMA Allogeneic CAR T Cell Therapy in Patients With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=136 | Active, not recruiting | Sponsor: Allogene Therapeutics | Trial completion date: Jan 2027 ➔ Jul 2025 | Trial primary completion date: Jan 2024 ➔ Jul 2025 | Recruiting ➔ Active, not recruiting

CAR T-Cell Therapy • Enrollment closed • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

DURABLES RESPONSES WITH ANTI-CD19 ALLOGENEIC CAR T ALLO-501/501A IN PHASE 1 TRIALS OF RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA (R/R LBCL) (ICML 2023) - P1, P1/2 | "New data document the durability of responses achieved with ALLO-501/501A following conditioning with fludarabine (F), cyclophosphamide (C), and ALLO-647 (A). ALLO-501/501A following FCA conditioning provided durable responses with a manageable safety profile in autologous CAR T-naïve pts with r/r LBCL. Durable complete remissions continue in 9 pts with the longest ongoing response at 29.6 months. These findings support broader evaluation of ALLO-501A/ALLO-647 in the ongoing, first, potentially pivotal phase 2 trial (ALPHA2) of allogeneic CAR T therapy."

P1 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A phase 1 multicenter study (TRAVERSE) evaluating the safety and efficacy of ALLO-316 following conditioning regimen in pts with advanced or metastatic clear cell renal cell carcinoma (ccRCC) (AACR 2023) - P1 | "Due to the high incidence (~80%) of CD70 antigen expression in primary and mRCC, yet limited expression in normal tissue, ccRCC is an attractive proof-of-concept tumor for CD70 directed allogeneic CAR T. TRAVERSE (NCT04696731), a first-in-human trial, seeks to identify a maximum tolerated dose (MTD) of ALLO-316 after conditioning with fludarabine/cyclophosphamide with/without ALLO-647 in pts with advanced or metastatic ccRCC. ALLO-316, an allogeneic CAR T cell product targeting CD70 in advanced mRCC, is demonstrating encouraging antitumor activity and a manageable safety profile. A single administration of ALLO-316 could be an effective treatment for pts with CD70+ solid tumors, including RCC, and hematologic malignancies. The MTD for ALLO-316 in TRAVERSE will support Phase 2 trial design."

Clinical • IO biomarker • Metastases • P1 data • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Hematological Malignancies • Oncology • Renal Cell Carcinoma • Solid Tumor • CD70