Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or Refractory Multiple Myeloma (UNIVERSAL)

Conditions

Relapsed/Refractory Multiple Myeloma

Brief summary

The purpose of the UNIVERSAL study is to assess the safety, efficacy, cell kinetics, and immunogenicity of ALLO-715 with or without Nirogacestat in adults with relapsed or refractory multiple myeloma after a lymphodepletion regimen of ALLO-647 in combination with fludarabine and/or cyclophosphamide, or ALLO-647 alone.

Daouda Abba Moussa, Mario Vazquez, Christine Chable-Bessia, Vincent Roux-Portalez, Elia Tamagnini et al. (21 authors)

Emerging Microbes & Infections2024-11-253 citations

10.1080/22221751.2024.2432345

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

Sham Mailankody, Jeffrey Matous, Michaela Liedtke, Surbhi Sidana, Olalekan O. Oluwole et al. (19 authors)

Blood2022-11-1510 citations

10.1182/blood-2022-158231

Universal Updated Phase 1 Data Validates the Feasibility of Allogeneic Anti-BCMA ALLO-715 Therapy for Relapsed/Refractory Multiple Myeloma

Sham Mailankody, Michaela Liedtke, Surbhi Sidana, Jeffrey Matous, Saurabh Chhabra et al. (21 authors)

Blood2021-11-0547 citations

10.1182/blood-2021-145572

Safety and PK/PD of ALLO-647, an anti-CD52 antibody, with fludarabine (Flu)/cyclophosphamide (Cy) for lymphodepletion in the setting of allogeneic CAR-T cell therapy.

Michael Tees, Sattva S. Neelapu, Parameswaran Hari, Sham Mailankody, David B. Miklos et al. (14 authors)

Journal of Clinical Oncology2021-05-2012 citations

10.1200/jco.2021.39.15_suppl.2527

Global Perspective on the Development of Genetically Modified Immune Cells for Cancer Therapy.

Pinte L, Cunningham A, Trébéden-Negre H, Nikiforow S, Ritz J.

2021-02-156 citations

10.3389/fimmu.2020.608485

Universal: An Allogeneic First-in-Human Study of the Anti-Bcma ALLO-715 and the Anti-CD52 ALLO-647 in Relapsed/Refractory Multiple Myeloma

Sham Mailankody, Jeffrey Matous, Michaela Liedtke, Surbhi Sidana, Shahbaz A. Malik et al. (13 authors)

Blood2020-11-0470 citations

10.1182/blood-2020-140641

Interventions

GENETICALLO-715

ALLO-715 is an allogeneic CAR T cell therapy targeting BCMA

BIOLOGICALALLO-647

ALLO-647 is a monoclonal antibody that recognizes a CD52 antigen

DRUGFludarabine

Chemotherapy for lymphodepletion

DRUGCyclophosphamide

Chemotherapy for lymphodepletion

DRUGNirogacestat

a small molecule, selective, reversible, noncompetitive inhibitor of γsecretase (GSI) that increases BCMA target density on the surface of multiple myeloma cells.

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Documented diagnosis of relapsed/refractory multiple myeloma (MM) with measurable disease (serum, urine, or free light chain \[FLC\]) per International Myeloma Working Group (IMWG) criteria * At least 3 prior lines of MM therapy, including a proteasome inhibitor, immunomodulatory agent, and anti-CD38 antibody (unless contraindicated), and refractory to the last treatment line. * Eastern Cooperative Oncology Group (ECOG) 0 or 1 * Absence of donor (product)-specific anti-HLA antibodies * Adequate hematologic, renal, hepatic, pulmonary, and cardiac function

Exclusion criteria

* Current or history of Central Nervous System (CNS) involvement of myeloma or plasma cell leukemia * Clinically significant CNS disorder * Current or history of thyroid disorder * Autologous stem cell transplant within the last 6 weeks, or any allogeneic stem cell transplant * Prior treatment with anti-BCMA therapy, any gene therapy, any genetically modified cell therapy, or adoptive T cell therapy * History of HIV infection or acute or chronic active hepatitis B or C infection * Patients unwilling to participate in an extended safety monitoring period Additional

Design outcomes

Primary

Measure	Time frame	Description
Proportion of subjects experiencing Dose Limiting Toxicities at increasing doses of ALLO-715	28 Days	Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715.
To assess the overall safety profile and tolerability of ALLO-647 in combination with Fludarabine and/or cyclophosphamide or ALLO-647 alone, prior to ALLO-715 to confirm the dose of ALLO-647.	33 days	The proportion of subjects in a dose cohort with DLTs of ALLO-647
To assess the overall safety profile and tolerability of nirogacestat given concomitantly with ALLO-715 following lymphodepletion with Flu/ Cy/ ALLO-647.	28 days	Dose limiting toxicities are defined as ALLO-715-related adverse events with onset within 28 days following infusion of ALLO-715.

Secondary

Measure	Time frame	Description
Pharmacokinetics of ALLO-647	up to 60 months	Serum concentration levels of ALLO-647
Pharmacokinetics of nirogacestat	up to 60 months	Serum concentration levels of nirogacestat
Incidence of immunogenicity against ALLO-715 and ALLO-647	up to 60 months	detection and levels of anti-drug antibodies
Cellular kinetics of ALLO-715	up to 60 months	Levels of anti-BCMA CAR T cells in blood
Anti-tumor activity of ALLO-715	up to 60 months	overall response rate
To evaluate the expression of BCMA in bone marrow plasma cells with and without nirogacestat	up to 60 months	Overall response rate of ALLO-715 with and without Nirogacestat
Immune monitoring after lymphodepletion regimen	up to 60 months	Detection of the following circulating cells: T cell subset, B lymphocytes, and NK cells
antitumor activity of ALLO-715 in combination with nirogacestat	up to 60 months	overall -response rate (ORR)
Cellular kinetics of ALLO-715 in combination with nirogacestat	up to 60 months	Levels of anti-BCMA CAR T cells in blood

Countries

United States

Outcome results

None listed