Clinical Trial 23380

• Overview

  Study Title:

  A Seamless Phase 1/2 Study to Evaluate the Safety and Efficacy of Mesothelin-Targeting Autologous Logic-gated Tmod CAR T Protducts in Heterozygous HLA-A*02 Adult with Recurrent Unresectable, Locally Advanced, or Metastatic Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression

  Summary:

  The goal of this study is to test A2B694, 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), ovarian cancer (OVCA), mesothelioma (MESO), and other solid tumors that express MSLN and have lost HLA-A*02 expression.

  Objective:

  Phase 1 Primary Objectives To evaluate the safety and tolerability of A2B694 To determine the recommended Phase 2 dose (RP2D) of A2B694 Phase 2 Primary Objective To evaluate the efficacy of A2B694 Secondary Objectives (Phase 1 and 2) To evaluate the efficacy of A2B694 across all cohorts and within disease cohorts To evaluate the safety of A2B694 for each tumor type To evaluate the manufacturing feasibility of A2B694 Phase 1: To evaluate biomarker data to correlate with clinical outcomes and guide RP2D selection To evaluate systemic cytokine release after A2B694 administration Phase 2: To evaluate biomarkers such as PK, PD, and immunogenicity To evaluate replication competent lentivirus (RCL) detected in blood samples

• Treatments

  Therapies:

  Cell Therapy; Chemotherapy (NOS)

  Medications:

  A2B543 (); A2B694 (); IL-2 (Interleukin-2); MESNA (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  Key Inclusion Criteria:
  • 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), 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, OVCA, MESO, or other solid tumors with MSLN 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.
  • ECOG performance status of 0 to 1.
  • Life expectancy of ≥3 months.
  • Willing to comply with study schedule of assessments including long term safety follow up.
  • Other inclusion criteria may apply.

• Exclusion Criteria

  Key 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.
  • MESO with pleural involvement extending into the peritoneum.
  • Cancer therapy within 3 weeks or 3 half lives of A2B694 infusion.
  • Radiotherapy within 28 days of A2B694 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.
  • History of interstitial lung disease including drug-induced interstitial lung disease and radiation pneumonitis that requires treatment with prolonged steroids or other immune suppressive agents within 1 year.
  • 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 A2B694.
  • Other exclusion criteria may apply.

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