MC# 20-11 - A Phase 1b/2, Multicenter, Open-Label Study of DSP-7888 Dosing Emulsion in Combination with Immune Checkpoint Inhibitors Nivolumab or Pembrolizumab in Adult Patients with Advanced Solid Tumors

  • Agent(s): DSP-7888
  • Disease Type(s): Ovarian, Fallopian Tube, Peritoneal
  • Phase(s): II
  • Drug Classification(s): Targeted Therapy, Gene Therapy
  • Molecular Target(s): WT1

Mechanism of Action

DSP-7888, a peptide cancer vaccine comprised of peptides derived from the Wilms tumor gene 1 (WT1) protein, may induce a specific cytotoxic T-lymphocyte (CTL) response against WT1-overexpressing tumor cells and also induces a helper T-lymphocyte-mediated immune response against WT1 expressing tumor cells.

Purpose

In this study, the sponsor and investigators want to learn:

  • About the safety and tolerability of DSP-7888
  • How proteins that indicate the status of your disease are affected with use of DSP-7888
  • If DSP-7888 prevents or delays tumor growth or shrinks existing tumors
Inclusion Criteria
  • Patients must be female ≥ 18 years of age, able to understand study procedures, and subsequently agreed to participate in the study by providing a written informed consent obtained prior to any prescreening and screening procedures that are not standard of care
  • Patients must be positive for at least 1 of the following HLA as assessed by central lab:
    • HLA-A*02:01
    • HLA-A*02:06
    • HLA-A*24:02
  • Patients must have histologically diagnosed high-grade (Grade 2 or 3) serous epithelial ovarian, fallopian tube, or primary peritoneal cancer
  • Patients must be considered platinum resistant to last administered platinum-based therapy, defined as patient relapsed within 6 months after last dose of platinum-based therapy
  • Patients must have completed at least 1 but no more than 3 prior lines of therapy for serous epithelial ovarian, fallopian tube, or primary peritoneal cancer;
    • Maintenance is not considered a separate line of treatment (even if patients with BRCA mutation positive received PARP-inhibitor following induction therapy with a platinum doublet including bevacizumab, etc)
    • Neoadjuvant or adjuvant systemic therapy counts as one line of therapy respectively
    • Patients must have received at least one platinum-based therapy
  • Patients must have progression disease after last therapy and have measurable disease according to RECIST (v.1.1)
  • Patients must have an ECOG performance status of 0 or 1
  • Patients must have adequate organ function, defined as follows:
    • Absolute neutrophil count (ANC) ≥ 1,500/μL (without granulocyte-colony stimulating factor (G-CSF))
    • Platelets ≥ 100,000/μL (without transfusion)
    • Hemoglobin ≥ 9.0 g/dL (without transfusion)
    • Serum creatinine ≤ 1.5 × ULN OR estimated glomerular filtration rate  ≥ 40 mL/min using the Cockcroft-Gault equation for patients with creatinine levels > 1.5 × ULN
    • Serum total bilirubin ≤ 1.5 × ULN
    • AST and ALT ≤ 2.5 × ULN OR ≤ 5 × ULN for patients with liver metastases
    • MUGA or echocardiogram with LVEF ≥ 40%
    • QTcF (QT corrected based on Fridericia’s equation) interval < 480 msec
    • International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN
    • Activated Partial Thromboplastin Time (aPTT) or Partial Thromboplastin Time (PTT) ≤ 1.5 × ULN 
  • Patients must provide a fresh tissue biopsy, if medically feasible, or archival tissue as either a formalin-fixed and paraffin embedded (FFPE) block or newly sectioned tissue on charged slides (equivalent to approximately 8-23 slides sectioned at 4-5μm thickness)
  • Patients of childbearing potential must have a negative serum or urine pregnancy test at screening
  • Patients must be either postmenopausal, free from menses for > 12 months, surgically sterilized, or willing to use adequate contraception to prevent pregnancy or must agree to abstain from heterosexual activity throughout the study, starting with enrollment through 150 days after the last dose of study treatment
  • Life expectancy ≥ 3 months
Exclusion Criteria
  • Primary platinum refractory patients defined as patients who experienced disease progression during the treatment with first-line platinum therapy
  • Patients with a known, untreated brain metastasis.  Patients with treated brain metastases must be clinically stable for 4 weeks after completion of treatment for brain metastases and have radiographic image documentation of stability.  Patients must have no clinical symptoms from brain metastases and not have required systemic corticosteroids > 5 mg/day prednisone or equivalent for at least 4 weeks prior to the first dose.
  • Patients who have received prior treatment with any other anti-PD-1, or PD-L1 or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms (examples of such drugs include but are not limited to antibodies against CTLA-4, LAG-3, IDO, PD-L1, IL-2R, GITR)
  • Patients who have received prior treatment with any other WT1-related agents including peptide vaccine, dendric cell vaccine, and gene therapy
  • Patients who have received treatment for ovarian cancer within the following time frame prior to the first dose of the study
    • Cytotoxic chemotherapy, hormonal therapy; ≤ 3 weeks
    • Targeted therapy except for monoclonal antibody; ≤ 3 weeks
    • Immune therapy, biologic therapy (eg, antibodies); ≤ 4 weeks
    • Other investigational agents: ≤ 4 weeks
    • Radiation therapy (except for localized radiotherapy for analgesic purpose) ≤ 4 weeks
    • Radiation therapy (localized radiotherapy for analgesic purpose) ≤ 1 week
    • Major surgery regardless of reason ≤ 4 weeks
  • Patients who have received a live vaccine within 4 weeks prior to the first dose
  • Any known additional malignancy that is progressing or requires active treatment with the exception of:
    • curatively treated basal cell or squamous cell carcinoma of skin
    • curatively treated superficial bladder cancer, carcinoma in situ of the cervix,
    • any another cancer from which the patient has been disease free for ≥ 3 years without any active treatment that, in the opinion of the Investigator and medical monitor for the Sponsor, will not affect patient’s outcome in the setting of the current diagnosis.
  • Patients who have not recovered to < CTCAE Grade 2 or baseline from toxic effect (with exception of alopecia) of prior cancer therapy
  • Patients who have an active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance dose of corticosteroids (> 5 mg/day prednisone or equivalent) or any other forms of immunosuppressive therapy within 7 days prior to the first dose of study drug
  • Positive serology for HIV infection, active hepatitis B, or hepatitis C
    • In cases of negative results for HepB surface antigen with positive HepB core antibody, hepatitis B virus (HBV) DNA greater than the lower limits of detection is not acceptable
  • Patients who have a known history of bacillus tuberculosis (TB)
  • Patients with impaired cardiac function or clinically significant cardiac disease;
    • New York Hospital Association Class III or IV cardiac disease, including preexisting clinically significant ventricular arrhythmia, congestive heart failure, or cardiomyopathy
    • Unstable angina pectoris ≤ 6 months before study participation
    • Myocardial infarction or stroke ≤ 6 months before study participation
  • Patients who have an interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management
  • Patients with infections that have required treatment with systemic antibiotics within 7 days prior to the first dose of protocol therapy
  • Patients with any psychiatric condition, substance abuse disorder, or social situation that would interfere with a patient’s cooperation with the study requirements and schedule
  • Patients with any condition that would, in the investigator’s judgment, interfere with full participation including administration of study drugs, attending required visits or interfere with interpretation of study data
  • Patients who are pregnant or breastfeeding
  • Patients who have a known hypersensitivity to DSP-7888, pembrolizumab, their components, or their excipients
  • Patient has dyspnea at rest (CTCAE ≥ Grade 3) or has required supplemental oxygen within 2 weeks of study enrollment

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/show/NCT03311334

Contact Us About This Trial

Reach out to us by sharing your info in the form below or give us a call at 972-566-3000.

Re: MC# 20-11