Clinical trial NCT05736731: A Study to Evaluate the Safety and Efficacy of A2B530, a Logic-gated CAR T, in Participants With Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression
Official title: A Phase 1/2 Study to Evaluate the Safety and Efficacy of A2B530, an Autologous Logic-gated Tmod™ Chimeric Antigen Receptor T Cell (CAR T), in Heterozygous HLA-A*02 Adult Subjects With Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors That Express CEA and Have Lost HLA-A*02 Expression
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor, Adult
Solid Tumor
Pancreatic Cancer
Pancreatic Neoplasms
Pancreas Cancer
Non Small Cell Lung Cancer
Non Small Cell Lung Cancer Recurrent
Non-Small Cell Squamous Lung Cancer
NSCLC
NSCLC, Recurrent
Colorectal Cancer
Colorectal Neoplasms
Colorectal Adenocarcinoma
CRC
Colorectal Cancer Metastatic
Cancer
Keywords: CAR T Cell
Solid Tumors
autologous
T cell
Carcinoembryonic Antigen
CEA
HLA-A2
Solid Tumors Expressing CEA
Pancreatic Cancer
PANC
CRC
Colorectal Cancer
NSCLC
Non-Small Cell Lung Cancer
Lead sponsor: A2 Biotherapeutics Inc.
Sponsor class: INDUSTRY
Collaborators: name: Tempus AI
First posted: 2023-02-21
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this study is to test A2B530,an autologous logic-gated Tmod™ CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC), pancreatic cancer (PANC), non-small cell lung cancer (NSCLC), and other solid tumors that express CEA and have lost HLA-A\*02 expression.

The main questions this study aims to answer are:

* Phase 1: What is the maximum or recommended dose of A2B530 that is safe for patients
* Phase 2: Does the recommended dose of A2B530 kill the solid tumor cells and protect the patient's healthy cells

Participants will be required to perform study procedures and assessments, and will also receive the following study treatments:

* Enrollment and Apheresis in BASECAMP-1 (NCT04981119)
* Preconditioning Lymphodepletion (PCLD) Regimen
* A2B530 Tmod CAR T cells at the assigned dose

Detailed description: This is a phase 1/2, multi-center, open-label study that enrolls adult subjects with recurrent unresectable, locally advanced, or metastatic (considered non-curative) CRC, NSCLC, PANC, or other solid tumors with CEA expression. Subjects must be germline HLA-A\*02 heterozygous, with tumors that express CEA and somatic loss of HLA-A\*02. The purpose of Phase 1 of this study is to determine the safety and the optimal dose of A2B530 (after PCLD) in participants with solid tumor disease. The purpose of Phase 2 of this study is to determine the further safety and efficacy (how well it treats the solid tumor disease) of A2B530.

The treatment available for these cancers and other solid tumors can be toxic, debilitating, and fatal. In the recurrent unresectable, locally advanced, or metastatic setting, the intent of standard of care treatment is typically palliative rather than curative, and has not changed significantly in several decades. A2 Bio hypothesizes that A2B530 Tmod CAR T-cell therapy will enable the killing of tumor target cells (those cells that express CEA and have LOH for HLA-A\*02 protein). Additionally, normal healthy cells that maintain HLA-A\*02 expression and co-express CEA (eg, gut mucosal tissue) will not be targeted due to the blocker portion of the Tmod CAR T cell that acts as a self-regulated safety switch that protects normal tissue from damage. A2 Bio believes this will provide a therapeutic safety window compared to previous solid tumor targeting therapies. This hypothesis will be explored in the study.

Participants for this study must enroll and have their T cells collected (apheresis) in the pre-screening BASECAMP-1 study (NCT04981119). T cells are collected, processed and stored for each participant. Upon disease progression the participant may screen for this study (EVEREST-1) and the participant's T cells are then manufactured and infused following PCLD regimen. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to EVEREST-1 based on their own disease course.

Eligibility criteria: Key Inclusion Criteria:

1. Appropriately enrolled in the BASECAMP-1 A2 Biotherapeutics, Inc. study, with tissue demonstrating LOH of HLA-A\*02:01 by NGS (whenever possible from the primary site), successful apheresis and PBMC processing, and with sufficient stored cells available for Tmod CAR T-cell therapy
2. Histologically confirmed recurrent unresectable, locally advanced, or metastatic CRC, NSCLC, PANC, or other solid tumors associated with CEA expression. Measurable disease is required with lesions of \>1.0 cm by computed tomography (CT). (Soluble CEA is not acceptable as the sole measure of disease).
3. Received previous required therapy for the appropriate solid tumor disease as described in the protocol
4. Has adequate organ function as described in the protocol
5. ECOG performance status of 0 to 1
6. Life expectancy of ≥3 months
7. Willing to comply with study schedule of assessments including long term safety follow up

Key Exclusion Criteria:

1. Has disease that is suitable for local therapy or able to receive standard of care therapy that is therapeutic and not palliative
2. Prior allogeneic stem cell transplant
3. Prior solid organ transplant
4. Cancer therapy within 3 weeks or 3 half lives of A2B530 infusion
5. Radiotherapy within 28 days of A2B530 infusion
6. Unstable angina, arrhythmia, myocardial infarction, or any other significant cardiac disease within the last 6 months
7. Any new symptomatic pulmonary embolism (PE) or a deep vein thrombosis (DVT) within 3 months of enrollment. Therapeutic dosing of anticoagulants is allowed for history of PE or DVT if greater than 3 months from time of enrollment, and adequately treated.
8. Requires supplemental home oxygen
9. Females of childbearing potential who are pregnant or breastfeeding
10. Subjects, both male and female, of childbearing potential who are not willing to practice birth control from the time of consent through 6 months post infusion of A2B530

Primary outcomes:
measure: Phase 1: Rate of adverse events and dose limiting toxicities (DLTs) by dose level
timeFrame: From the time of Informed consent until 24 months (2 years) post A2B530 infusion.
measure: Phase 1: Recommended Phase 2 Dose (RP2D)
timeFrame: 21 days post A2B530 infusion
measure: Phase 2: The Overall Response Rate (ORR) for patients
timeFrame: 24 months post A2B530 infusion
Secondary outcomes:
measure: Persistence of A2B530
timeFrame: up to 24 months post A2B530 infusion
measure: Cytokine analysis
timeFrame: up to 24 months post A2B530 infusion
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner Health
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: NYU Langone Medical Center
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: A2 Biotherapeutics Inc.
name: Eric Ng, MD
role: STUDY_DIRECTOR
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