Clinical Trial 21622

• Overview

  Study Title:

  A Phase 1/1b Dose Escalation/Dose Expansion Study of PRGN-3007 UltraCAR-T Cells in Patients with Advanced Hematologic and Solid Tumor Malignancies

  Summary:

  The purpose of the study is to find out if an investigational drug called PRGN-3007 UltraCAR-T cells (PRGN-3007 T cells) can help people with ROR1-positive hematologic chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and solid tumor triple negative breast cancer (TNBC) malignancies.

  Objective:

  Primary Objectives: Phase I: To determine the MTD of PRGN-3007 in subjects with advanced ROR1+ hematologic malignancies and solid tumors Phase Ib: To evaluate the safety of PRGN-3007 administered at the MTD to subjects with advanced ROR1+ hematologic malignancies and solid tumors Secondary Objectives: -To determine the ORR and DCR in subjects with advanced ROR1+ hematologic malignancies and solid tumors following PRGN-3007 infusion using the assessments and criteria appropriate for their disease -To evaluate expansion and persistence of PRGN-3007 in blood and at the tumor site for 12 months following the initial dose of PRGN-3007 -To evaluate the time to onset and duration of response in subjects with a confirmed response Exploratory Objectives: -To characterize expression of cytokines and biomarkers in blood and tissue samples collected pre- and post-treatment with PRGN-3007 -To characterize changes in immune phenotype pre- and post-treatment PRGN-3007 -To examine minimal residual disease (MRD) in subjects that experience a response to PRGN-3007 infusion -To compare PRGN-3007 expression in blood and tumor following different lymphodepletion regimen

• Treatments

  Therapies:

  Cell Therapy; Chemotherapy (NOS); Therapy (NOS)

  Medications:

  Cetuximab (); Erbitux (Cetuximab); PRGN-3007 (); Tocilizumab (); cyclophosphamide (); cytoxan (cyclophosphamide); fludarabine (Fludarabine phosphate)

• Inclusion Criteria

  Key Inclusion Criteria:
  • Age 18 years and older
  • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1; or Karnofsky Performance Status (KPS) of ≥ 70%.
  • Life expectancy ≥ 12 weeks from the time of enrollment
  • Must have adequate organ function, as defined in protocol.
  • Patients must be at least 2 weeks or 5 half-lives (whichever is shorter) post systemic steroids prior to enrollment except as premedication for contrast allergy.
  • Negative serum pregnancy test for women of childbearing potential (WOCBP). Fertile male and female patients must be willing to use a contraceptive method before, during, and for at least 12 months after the last T cell infusion.
  • All patients must have the ability to understand and willingness to sign a written informed consent form (ICF).
  • Other criteria apply

• Exclusion Criteria

  Exclusion Criteria:
  • Patient has received any of the following treatments prior to leukapheresis: cytotoxic chemotherapy or radiation therapy within 14 days; an antineoplastic monoclonal antibody within prior 4 weeks; prior targeted therapy 14 days or 5 half-lives from the last dose whichever is shorter; or prior systemic inhibitory/stimulatory immune checkpoint molecule therapy (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists) within 3 half-lives; or has not recovered from (i.e., ≤ grade 1) adverse event (AE) caused by prior treatment. Exceptions include hydroxyurea, single agent vincristine or steroids for uncontrolled ALL.
  • Burkitt lymphoma is excluded.
  • Prior allogeneic hematopoietic stem cell transplant (HSCT) or donor lymphocyte infusion within 6 months prior to enrollment, current acute graft versus host disease grade 2-4 by Glucksberg criteria or severity B-D by by International Bone Marrow Transplant Registry (IBMTR) index or history of severe (grade 3-4) acute graft versus host disease.
  • Patients with a history of immunodeficiency (except for acquired hypogammaglobulinemia), patients with active autoimmune disease requiring systemic immunosuppressive therapy (i.e., > 15 mg of prednisone daily or equivalent), or patients who have received any other form of immunosuppressive therapy within 7 days prior to leukapheresis.
  • Patients with a history of autoimmune disease resulting in end-organ injury are not eligible unless attributable to primary disease which is target of this study.
  • Patient requires treatment with warfarin.
  • Patients who have contraindication to the lymphodepletion chemotherapy regimen.
  • Patient received a live vaccine administration within 4 weeks prior to leukapheresis.
  • Patient is currently participating in another investigation treatment study or has participated in a study of an investigational agent within 4 weeks prior to leukapheresis.
  • Patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing; those with a forced expiratory volume at one second(FEV1) of ≤ 65% or diffuse capacity lung for carbon monoxide (DLCO; corrected) > Patients with history of other active malignancy within 1 year prior to enrollment.
  • Patients with adequately resected basal or squamous cell carcinoma of the skin, non-melanoma skin cancer or carcinoma in situ (e.g., skin, cervix, bladder, breast), superficial bladder cancer, asymptomatic localized low grade prostate cancer for which watch-and-wait approach is standard of care, or any other cancer that has been in remission are eligible
  • History of concomitant genetic syndrome associated with bone marrow failure such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome
  • Known human immunodeficiency virus (HIV) seropositivity or active hepatitis B or C infection. A history of hepatitis B or C is permitted if the viral load is undetectable by quantitative assay
  • Ongoing uncontrolled serious infection, clinically significant cardiac disease (i.e.,symptomatic congestive heart failure, myocardial infarction, cardiac angioplasty or stenting, unstable angina pectoris, uncontrolled cardiac arrhythmia), poorly controlled pulmonary disease (no clinically significant pleural effusion), or psychiatric illness/social situations that would limit compliance with study requirements within 12 months prior to enrollment.
  • History of any central nervous system (CNS) disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome, or cerebral edema
  • History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months prior to enrollment
  • Other criteria apply

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