Details

Details

Title A Phase 1 Clinical Study of DSP-7888 Dosing Emulsion in Adult Patients with Advanced Malignancies

IRB BBI 1Y17

CC 17-910

Hospital Main Campus

Stage Advanced/Metastatic

Phase Phase 1

Disease Myelodysplastic Syndrome (MDS)

Drug DSP-7888

Description

Description

Primary Objective
  • To determine the safety, tolerability, and recommended Phase 2 dose (RP2D) of DSP-7888 Dosing Emulsion in adult patients with advanced malignancies when administered either intradermally or subcutaneously.
Secondary Objectives
  • To assess the preliminary antitumor activity of DSP-7888 Dosing Emulsion when administered to adult patients with advanced malignancies.
  • To assess preliminary antitumor responses, PFS for solid tumors and AML, time to transformation to AML or death for MDS, and OS.
Inclusion Criteria

Inclusion Criteria

Signed written informed consent must be obtained and documented according to International Council for Harmonisation (ICH) and local regulatory requirements.

  1. Patient has one of the following histologically or cytologically confirmed advanced malignancies:
    • AML (Patients with AML may have disease that is measurable by quantitative RT-PCR of WT1 transcript only)
    • MDS
    • glioblastoma multiforme (GBM)
    • melanoma
    • nonsmall cell lung cancer (NSCLC)
    • ovarian cancer
    • pancreatic cancer
    • sarcoma
    • renal cell carcinoma (RCC)
  2. Patient must meet at least one of the following criteria:
    • Has progressed or recurrent disease despite receiving appropriate standard therapy available to him/her for his/her given diagnosis
    • No standard therapy exists for this malignancy
    • Patient is intolerant of standard therapy and additional or alternative standard therapies either do not exist or have been exhausted
    • Patient is not a candidate for standard therapy and additional or alternative standard therapies either do not exist or have been exhausted
    • For AML and MDS patients: patient is not a candidate for allogeneic hematopoietic stem cell transplantation
  3. Patients must be positive for at least one of the following human leukocyte antigens:
    • HLA-A*02:01
    • HLA-A*02:06
    • HLA-A*24:02
  4. ≥ 18 years of age
  5. For patients with solid tumors, one of the following must apply:
    • Patient has measurable disease as defined by the immune-related response criteria (irRC)
    • Patient has ovarian cancer and has disease evaluable by CA-125 only
  6. For patients with solid tumors, the following criteria apply:
    • Hemoglobin ≥ 9.0 g/dl
    • Absolute lymphocyte count ≥ 1.0 x 109/L
    • Absolute neutrophil count ≥ 1.5 x 109/L
    • Platelets ≥ 100.0 x 109/L
  7. Patients with MDS must have been diagnosed as MDS by World Health Organization (WHO) (fourth edition) or French-American-British (FAB) classification
  8. Patients with MDS must have failed to respond to, or progressed after, adequate treatment with a hypomethylating agent (HMA), or had documented intolerance of an HMA, and must have an International Prognostic Scoring System (IPSS) score ≥ 1.5
  9. Patients with AML or MDS must have white blood cell (WBC) count ≤ 50,000/microliter. Hydroxyurea is allowed to achieve this change, but it must be discontinued a minimum of 5 days before baseline evaluation
  10. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
  11. Male or female patients of child-producing potential must agree to use contraception during the study and for 180 days after the last DSP-7888 Dosing Emulsion dose
  12. Females of childbearing potential must have a negative serum pregnancy test
  13. Total bilirubin of ≤ 2.0 mg/dL (≤ 3.0 mg/dL for patients with known Gilbert's syndrome)
  14. Aspartate aminotransferase (AST) ≤ 3.0 x the upper limit of normal (ULN) or < 5 x ULN if known liver metastases
  15. Alanine transaminase (ALT) ≤ 3.0 x the upper limit of normal (ULN) or < 5 x ULN if known liver metastases
  16. Creatinine ≤ 2.0 x ULN
  17. Life expectancy ≥ 3 months
  18. For patients with solid tumors, either archival tumor tissue must be available or patient must consent to undergo on study tumor biopsy before administration of first dose.
  19. Patients with MDS or AML are also required to have had a bone marrow aspirate or biopsy within 28 days before first dose.
  20. Adverse events (AEs) from prior treatments must have either resolved or must have been deemed irreversible.
  21. Left ventricular ejection fraction (LVEF) > 40%
  22. Resting pulse oximetry of 90% or higher
Exclusion Criteria

Exclusion Criteria

  1. Patient has an extensively disseminated primary glioblastoma.
  2. Patient has acute promyelocytic leukemia (APML).
  3. For AML and MDS patients: unable to provide either a bone marrow aspirate or bone marrow biopsy during screening.
  4. Patient has symptomatic brain metastases (ie, metastases that are accompanied by neurological symptoms or that require treatment with corticosteroids).
  5. Patient has an infection requiring treatment with systemic antibiotics or antiviral medication or has completed treatment for such an infection within 14 days before planned first dose of study drug. MDS patients requiring treatment with systemic antibiotics other than IV administration may be enrolled.
  6. Patient requires systemic, pharmacologic doses of corticosteroids (equivalent to > 10 mg prednisone/day). Note: Replacement doses (equivalent to ≤ 5 mg prednisone/day), and topical, ophthalmic, and inhalation steroids are permitted as needed. For patients requiring frequent blood product transfusions and with a history of transfusion reactions, patients receiving doses of corticosteroids necessary to prevent allergic reactions at the discretion of the Investigator may be enrolled.
  7. Patient has a positive test for Hepatitis B surface antigen, Hepatitis C antibody, human immunodeficiency virus HIV-1 antibody, or has a history of a positive result for Hepatitis C virus (HCV) or human immunodeficiency virus (HIV), unless the patient has completed a course of therapy for Hepatitis C and polymerase chain reaction (PCR) negative for HCV RNA.
  8. Patient has received any of the following treatments within the specified timeframes:
    • Surgery, radiotherapy, chemotherapy (including molecular-targeted drugs): 4 weeks (28 days)
    • Immunosuppressants or cytokine formulations (excluding G-CSF): 4 weeks (28 days)
    • Endocrine therapy or immunotherapy (including biological response modifier therapy): 2 weeks (14 days)
  9. Woman who is pregnant or lactating or has a positive pregnancy test at screening. If a woman has a positive pregnancy test, further evaluation may be conducted to rule out ongoing pregnancy to allow the patient to be eligible.
  10. Patient has any concurrent autoimmune disease or has a history of chronic or recurrent autoimmune disease; these include but are not limited to: multiple sclerosis, Grave's disease, vasculitis, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, myasthenia gravis, ankylosing spondylitis, Wegener's granulomatosis, ulcerative colitis, Crohn's disease, psoriasis requiring systemic therapy, pemphigus, temporal arteritis, dermatomyositis, Sj�gren's syndrome, Goodpasture's syndrome, interstitial pneumonitis, interstitial nephritis, or Henoch-Sch�nlein purpura.
    • A patient with a history of these conditions may be considered eligible if the condition is under good control such that there have been no symptoms or signs of recurrence or exacerbation in the 12 months before enrollment.
    • A patient with a history of these conditions may be considered eligible if they were considered to be secondary to prior treatment with checkpoint inhibitors and if the condition is under good control such that there have been no symptoms or signs of recurrent or exacerbation in the 6 months before enrollment.
  11. Patient has a medical history of frequent ventricular ectopy, e.g., non-sustained ventricular tachycardia (VT).
  12. Patient has, in the opinion of the treating Investigator, any concurrent conditions that could pose an undue medical hazard or interfere with the interpretation of the study results; these conditions include, but not limited to: concurrent congestive heart failure (New York Heart Association [NYHA] Class III or IV), concurrent unstable angina, concurrent cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation), recent (within the prior 6 months) myocardial infarction, acute coronary syndrome or stroke within the previous 6 months, concurrent severe obstructive pulmonary disease, concurrent hypertension requiring more than 2 medications for adequate control, or diabetes mellitus with more than 2 episodes of ketoacidosis in the prior 12 months.
  13. For patients with AML/MDS, patient has concurrent Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade ≥ 2 hemorrhage or a history of a CTCAE version 4.0 grade ≥ 2 hemorrhage within 14 days prior screening.
  14. Patient has concurrent pleural effusion, ascites, or pericardial fluid requiring drainage Note: Patient who had drain removal ≥ 14 days before planned first dose of study drug and has no sign of worsening is eligible.
  15. Patient has any other medical, psychiatric, or social condition, including substance abuse, that in the opinion of the Investigator would preclude compliance with the requirements of this study.
  16. Patients with 2 or more active malignancies (synchronous multiple cancers, or metachronous multiple cancers with a disease-free period of ≤ 5 years, with the exception of carcinoma in situ, mucosal carcinoma).
  17. Patient has had previous treatment with the study drug or other WT1-related immune therapy.
  18. Patient has history of allergy to any oily drug products.
  19. Patient has a known hypersensitivity to any of the components of the study drug.
  20. Patient has a QTcF (QT corrected based on Fridericia's equation) interval > 480 msec (CTCAE = Grade 2) or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening. (Patients with bundle branch block and a prolonged QTc interval should be reviewed by the Medical Monitor for potential inclusion.)
  21. Patient has dyspnea at rest (CTCAE ≥ Grade 3) or has required supplemental oxygen within 2 weeks of study enrollment.