ACE1831 in Adult Subjects With Relapsed/ Refractory CD20-expressing B-cell Malignancies

Sponsor

Acepodia Biotech, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05653271

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

ACE1831 is an off-the-shelf, allogeneic gamma delta T (gdT) cell therapy derived from healthy donors, that is under investigation for the treatment of CD20-expressing B-cell malignancies.

The ACE1831-001 study is an open-label, Phase I, first-in-human (FIH) study that aims to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, and efficacy of ACE1831 in patients with CD20-expressing Non-Hodgkin lymphoma.

Condition or Disease	Intervention/Treatment	Phase
B-cell Lymphoma Non Hodgkin Lymphoma DLBCL Primary Mediastinal Large B Cell Lymphoma Marginal Zone Lymphoma Follicular Lymphoma	Drug: Cyclophosphamide Drug: Fludarabine Drug: ACE1831 Drug: Obinutuzumab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

42 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1 Multicenter Study Evaluating the Safety and Efficacy of ACE1831, an Allogeneic CD20-conjugated Gamma Delta T-cell Therapy, in Adult Subjects With Relapsed/Refractory CD20-expressing B-cell Malignancies

Anticipated Study Start Date :

Jan 31, 2023

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Group A (ACE1831) ACE1831 dose escalation, monotherapy. Lymphodepleting regimen followed by escalating doses of ACE1831.	Drug: Cyclophosphamide Lymphodepleting agent Drug: Fludarabine Lymphodepleting agent Drug: ACE1831 Allogeneic gamma delta T (gdT) cell therapy
Experimental: Treatment Group B (ACE1831 and obinutuzumab) ACE1831 dose escalation, in combination with obinutuzumab. Lymphodepleting regimen followed by escalating doses of ACE1831, given in combination with obinutuzumab.	Drug: Cyclophosphamide Lymphodepleting agent Drug: Fludarabine Lymphodepleting agent Drug: ACE1831 Allogeneic gamma delta T (gdT) cell therapy Drug: Obinutuzumab Anti-CD20 monoclonal antibody

Arm

Intervention/Treatment

Experimental: Treatment Group A (ACE1831)

ACE1831 dose escalation, monotherapy. Lymphodepleting regimen followed by escalating doses of ACE1831.

Drug: Cyclophosphamide

Lymphodepleting agent

Drug: Fludarabine

Lymphodepleting agent

Drug: ACE1831

Allogeneic gamma delta T (gdT) cell therapy

Experimental: Treatment Group B (ACE1831 and obinutuzumab)

ACE1831 dose escalation, in combination with obinutuzumab. Lymphodepleting regimen followed by escalating doses of ACE1831, given in combination with obinutuzumab.

Drug: Cyclophosphamide

Lymphodepleting agent

Drug: Fludarabine

Lymphodepleting agent

Drug: ACE1831

Allogeneic gamma delta T (gdT) cell therapy

Drug: Obinutuzumab

Anti-CD20 monoclonal antibody

Outcome Measures

Primary Outcome Measures

Incidence of adverse events (AEs), Dose Limiting Toxicities (DLTs), adverse events of special interest (AESIs), and serious adverse events (SAEs) [2 years]
Change from baseline in ECOG status [1 year]
Change from baseline in physical examination results [1 year]
Number of subject with change from baseline clinically significant physical examination findings by dose level (descriptive)
Change from baseline clinical laboratory tests results [1 year]
Number of subjects with change from baseline clinically significant lab findings by dose level (descriptive)
Change from baseline in urinalysis results [1 year]
Number of subjects with change from baseline clinically significant urinalysis findings by dose level (descriptive)
Change from baseline in vital signs results [1 year]
Number of subjects with change from baseline clinical significant vital signs findings by dose level (descriptive)
Change from baseline in electrocardiogram (ECG) results [1 month]
Number of subjects with change from baseline clinically significant ECG findings by dose level (descriptive)
Maximum Tolerated Dose (MTD) [1 month]

Secondary Outcome Measures

Persistence of ACE1831 after administration [1 month]
Half-life of ACE1831
Measure of anti-ACE1831 antibodies after administration [1 month]
Titration of anti-ACE1831 antibodies after administration
Objective Response Rate (ORR) [2 years]
Objective response of each patient's underlying lymphoma, duration of response, and progression-free survival all based on the revised IWG Response Criteria for Malignant Lymphoma

Other Outcome Measures

Pharmacodynamics of ACE1831 [2 years]
Serum levels of interferon-γ, TNF-α, IL-2, IL-6, IL-8 and IL-10, as well as other potential biomarkers

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

CD20-positive B-cell NHL that is persistent or progressive after having received at least 2 prior systemic therapies per NCCN guidelines
At least 1 measurable lesion according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
Adequate hematologic and renal, hepatic, and cardiac function
Oxygen saturation via pulse oxygenation ≥ 92% at rest on room air

Key Exclusion Criteria:

Prior treatment with a genetically modified cell therapy product targeting CD20
Autologous stem cell transplant within 6 weeks of informed consent or history of allogeneic stem cell transplantation
History of central nervous system (CNS) lymphoma or primary CNS lymphoma
History or presence of clinically relevant CNS disorder (e.g. epilepsy)
Clinically significant active infection
Currently active, clinically significant cardiovascular disease
Human Immunodeficiency virus (HIV) infection, active hepatitis B infection, or hepatitis C infection
History of other malignancies with the exception of certain treated malignancies with no evidence of disease
Primary immunodeficiency disorder
Pregnant or lactating female
Any medical, psychological, familial, or sociological conditions that, in the opinion of the Investigator or Sponsor Medical Monitor, would impair the ability of the subject to receive study treatment, comply with study requirements, or understanding of the informed consent