Clinical Trial 22556

• Overview

  Study Title:

  EVEREST-1: 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

  Summary:

  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. 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.

  Objective:

  3.2.1 Phase 1 Primary Objectives To evaluate the safety and tolerability of A2B530 in subjects with recurrent unresectable, locally advanced, or metastatic CRC, NSCLC, PANC, and other solid tumors commonly associated with somatic LOH of HLA-A*02. To determine recommended Phase 2 dose (RP2D) of A2B530 with optimized PCLD regimen of cyclophosphamide and fludarabine To evaluate the DLT rate 3.2.2 Phase 1 Secondary Objectives To evaluate efficacy of A2B530 in the subject population To evaluate the manufacturing feasibility of A2B530 To evaluate biomarker data to correlate with clinical outcomes and guide RP2D selection To evaluate systemic cytokine release after A2B530 administration. To evaluate subject incidence of replication competent lentivirus (RCL) detected in blood samples 3.2.3 Phase 2 Primary Objectives To evaluate the efficacy of A2B530 as assessed by ORR using RESCIST 1.1 by independent central review for all tumor types and individual tumor cohorts. 3.2.4 Phase 2 Secondary Objectives To evaluate the safety of A2B530 for each tumor type as assessed by subject incidence of treatment-emergent adverse events (AEs) including DLTs To evaluate the manufacturing feasibility of A2B530 To evaluate OS To evaluate biomarkers such as PK, PD, and immunogenicity To evaluate subject incidence of RCL detected in blood samples 3.2.5 Phase 2 Exploratory Objectives To evaluate potential biomarkers based on the assessment of samples from apheresis through final product, blood cells, tumor and normal tissue, and the hypothesized actions of the investigational product To evaluate systemic cytokine release after A2B530 administration

• Treatments

  Therapies:

  Cell Therapy; Chemotherapy (NOS)

  Medications:

  A2B530 (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  Inclusion Criteria:
  • 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
  • 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).
  • Received previous required therapy for the appropriate solid tumor disease as described in the protocol
  • Has adequate organ function as described in the protocol
  • ECOG performance status of 0 to 1
  • Life expectancy of greater than or equal to 3 months
  • Willing to comply with study schedule of assessments including long term safety follow up

• Exclusion Criteria

  Exclusion Criteria:
  • 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 A2B530 infusion
  • Radiotherapy within 28 days of A2B530 infusion
  • Unstable angina, arrhythmia, myocardial infarction, or any other significant cardiac disease within the last 6 months
  • 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.
  • Requires supplemental home oxygen
  • Females of childbearing potential who are pregnant or breastfeeding
  • 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

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