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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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B-cell Lymphoma, Non Hodgkin Lymphoma, DLBCL, Primary Mediastinal Large B Cell Lymphoma, Marginal Zone Lymphoma, Follicular Lymphoma

Intervention / Treatment
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* Drug: Cyclophosphamide
* Drug: Fludarabine
* Drug: ACE1831
* Drug: Obinutuzumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Number of subject with change from baseline clinically significant physical examination findings by dose level (descriptive) | 1 year | 
| Change from baseline clinical laboratory tests results | Number of subjects with change from baseline clinically significant lab findings by dose level (descriptive) | 1 year | 
| Change from baseline in urinalysis results | Number of subjects with change from baseline clinically significant urinalysis findings by dose level (descriptive) | 1 year | 
| Change from baseline in vital signs results | Number of subjects with change from baseline clinical significant vital signs findings by dose level (descriptive) | 1 year | 
| Change from baseline in electrocardiogram (ECG) results | Number of subjects with change from baseline clinically significant ECG findings by dose level (descriptive) | 1 month | 
| Maximum Tolerated Dose (MTD) |  | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistence of ACE1831 after administration | Half-life of ACE1831 | 1 month | 
| Measure of anti-ACE1831 antibodies after administration | Titration of anti-ACE1831 antibodies after administration | 1 month | 
| Objective Response Rate (ORR) | 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 | 2 years |