About this trial
The goal of this study is to test A2B395, an allogeneic logic-gated Tmod™ CAR T-cell product in subjects with solid tumors including colorectal cancer (CRC), non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), triple-negative breast cancer (TNBC), renal cell carcinoma (RCC) and other solid tumors that express EGFR and have lost HLA-A\*02 expression.
The main questions this study aims to answer are:
* Phase 1: What is the recommended dose of A2B395 that is safe for patients * Phase 2: Does the recommended dose of A2B395 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 in BASECAMP-1 (NCT04981119) * Preconditioning lymphodepletion (PCLD) regimen * A2B395 Tmod CAR T cells at the assigned dose
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Appropriately enrolled in the BASECAMP-1 A2 Biotherapeutics, Inc. study, with tissue demonstrating LOH of HLA-A*02 by NGS (whenever possible from the primary site).
Histologically confirmed recurrent unresectable, locally advanced, or metastatic CRC, NSCLC, HNSCC, TNBC, RCC, or other solid tumors with EGFR expression. Measurable disease is required with lesions of ≥1.0 cm by CT.
Received previous required therapy for the appropriate solid tumor disease as described in the protocol
Has adequate organ function as described in the protocol
Disqualifiers
Has disease that is suitable for local therapy or able to receive standard of care therapy that is therapeutic and not palliative
Prior allogeneic stem cell transplant
Prior solid organ transplant
Cancer therapy within 3 weeks or 3 half lives of A2B395 infusion
Trial design
Single group
Treatments tested in this trial
A2B395
Biological/VaccineAllogeneic logic-gated Tmod CAR T cells
xT CDx with HLA-LOH assay
Diagnostic testAn investigational next generation sequencing (NGS) in vitro diagnostic (IVD) medical device
Treatment groups
Trial outcomes
Primary outcomes
Phase 1: Rate of adverse events and dose limiting toxicities (DLTs) by dose level
Adverse events and toxicity will be evaluated according to the Cancer Therapy Evaluation Program Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (or current version). Cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and graft versus host disease (GvHD) events will be graded according to the criteria described in the current protocol.
Phase 1: Recommended phase 2 dose (RP2D)
The RP2D will be identified utilizing a BOIN study design in addition to considering safety and biomarker analysis.
Phase 2: The overall response rate (ORR) for patients
The ORR will be evaluated per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and assessed by independent central review.
Secondary outcomes
Persistence of A2B395
Number of A2B395 Tmod CAR T cells present in participants treated with A2B395 as assessed by polymerase chain reaction (PCR) (or similar method) on participant blood samples
Cytokine analysis
Cytokine levels such as interferon-gamma (IFN-γ) in participants treated with A2B395 assessed by cytokine analysis on participant blood samples
Cytokine analysis
Cytokine levels such as interleukin-6 (IL-6) in participants treated with A2B395 assessed by cytokine analysis on participant blood samples
Sponsors and contacts
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