A Study of DSP-7888 Dosing Emulsion in Combination With Bevacizumab in Patients With Recurrent or Progressive Glioblastoma Following Initial Therapy

A Randomized, Multicenter, Adaptive Phase 3 Study of DSP-7888 Dosing Emulsion in Combination With Bevacizumab Versus Bevacizumab Alone in Patients With Recurrent or Progressive Glioblastoma Following Initial Therapy (WIZARD 201G)

This is an event driven, adaptive design, a randomized, active-controlled, multicenter, open-label, parallel groups, Phase 3 study of DSP-7888 Dosing Emulsion plus Bevacizumab versus Bevacizumab alone in patients with recurrent or progressive glioblastoma multiforme (GBM) following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy.

Study Overview

• Status: Completed
• Conditions: Glioblastoma
• Intervention / Treatment: Drug: DSP-7888 Dosing Emulsion; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 221
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • University of Sherbrooke
• Japan
  • Hiroshima, Japan, 734-8551
    • Hiroshima University Hospital
  • Kumamoto, Japan, 860-8556
    • Kumamoto University Hospital
  • Kyoto, Japan, 602-8566
    • University Hospital, Kyoto Prefectural University of Medicine
  • Kyoto, Japan, 612-8555
    • National Hospital Organization Kyoto Medical Center
  • Shinjuku-Ku, Japan, 162-8666
    • Tokyo Women's Medical University Hospital
  • Yamagata, Japan, 990-9585
    • Yamagata University Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Kagoshima
    • Kagoshima-shi, Kagoshima, Japan, 890-8520
      • Kagoshima University Hospital
  • Niigata
    • Chuo Ku, Niigata, Japan, 951-8520
      • Niigata University Medical and Dental Hospital
  • Osaka
    • Chuo Ku, Osaka, Japan, 541-8567
      • Osaka International Cancer Institute
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • The University of Tokyo Hospital
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea, Seoul St. Mary's Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06273
    • Gangnam Severance Hospital
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
• Taiwan
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
  • Taoyuan City, Taiwan
    • Chang Gung Memorial Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arizona
    • Tucson, Arizona, United States, 85718
      • Center for Neurosciences
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Highlands Oncology Group
  • California
    • La Jolla, California, United States, 92093
      • UCSD- Moores Cancer Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center
    • Orange, California, United States, 92868
      • Neuro-Oncology/ US Irvine Medical Center
    • Santa Barbara, California, United States, 93105
      • Sansum Clinic
    • Santa Monica, California, United States, 90404
      • John Wayne Cancer Institute
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont brain tumor center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky / Department of Internal Medicine / Markey Cancer Center
    • Louisville, Kentucky, United States, 40202
      • Norton Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Abbott Northwestern Hospital
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurosciences Research Center
    • New York, New York, United States, 10021
      • Weill Cornell Medicine
    • New York, New York, United States, 10032
      • Columbia University Medical Center/ Neurological Institute of NY
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals of Cleveland
    • Toledo, Ohio, United States, 43606
      • University of Toledo
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hospital of the University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center (Upmc)
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Academic Medical Center Cancer Institute
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology Austin Midtown
    • Dallas, Texas, United States, 75246
      • Baylor Scott and White
    • Houston, Texas, United States, 77030
      • Houston Methodist
    • Houston, Texas, United States, 77030
      • Mischer Neuroscience Associates/Memorial Hermann Hospital
    • The Woodlands, Texas, United States, 77380
      • Renovatio Clinical
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists, Pc
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Medical Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients or their legal representatives must be able to provide written informed consent.
• Histologically confirmed diagnosis of supratentorial GBM (Grade 4 astrocytoma).
• Radiographic evidence of first recurrence or progression of GBM following primary therapy consisting of surgery (biopsy or resection) and chemoradiation; patients may have undergone a second debulking surgery following initial recurrence or progression. Patients whose tumors are O6 methyl guanyl-methyltransferase (MGMT) methylated-promoter negative need not have received chemotherapy in the past to be eligible.
• Human leukocyte antigen type HLA-A*02:01, HLA-A*02:06, or HLA-A*24:02.
• Age ≥18.
• KPS score of ≥60.
• Serum creatinine value <2X the upper limit of normal (ULN) for the reference laboratory.
• Alanine aminotransferase/aspartate aminotransferase <3X the ULN and total bilirubin <2× the ULN for the reference laboratory.
• Men and women of childbearing potential must agree to use a reliable method of contraception (oral contraceptives, implantable hormonal contraceptives, or double barrier method) or agree to completely refrain from heterosexual intercourse for the duration of the study and for 180 days following the last dose of DSP-7888 Dosing Emulsion.
• Patients must have recovered from the effect of all prior therapy to Grade 2 or less.
• Patients must be at least 28 days from any major surgery, and any surgery incisions or wounds must be completely healed.
• Patients must be at least 12 weeks from the completion of prior radiation therapy (RT) in order to discriminate pseudo progression of disease from progression.
• Patients must be at least 4 weeks from the completion of prior systemic or intracranial chemotherapy.
• Patients must stop Novo-TTF treatment one day prior to study therapy (no washout period is needed). However, any wounds from TTF must be adequately healed per Inclusion Criterion #11.15. For patients who are not receiving therapeutic anticoagulation treatment, an international normalized ratio (INR) and a PTT ≤ 1.5 × the ULN; patients who are receiving anticoagulation treatment should be on a stable dose.
• Patient's left ventricular ejection fraction (LVEF) > 40%. 17. Patient has a resting pulse oximetry of 90% or higher.

Exclusion Criteria:

Patients with any of the following will be excluded from the study:

• Prior therapy with Bev.
• Patients with secondary GBM.
• Any anti-neoplastic therapy, including RT, for first relapse or recurrence.
• Evidence of leptomeningeal spread of tumor or any history, presence, or suspicion of metastatic disease extracranially.
• Evidence of impending herniation on imaging.
• Has known multifocal disease. Multifocal disease is defined as discrete sites of disease without contiguous T2/FLAIR abnormality that require distinct radiotherapy ports. Satellite lesions that are associated with a contiguous area of T2/FLAIR abnormality as the main lesion(s) and that are encompassed within the same radiotherapy port as the main lesion(s) are permitted.
• Patients with infections that have required treatment with systemic antibiotics within 7 days of first dose of protocol therapy.
• The need for systemic glucocorticoids in doses in excess of 4 mg/day of dexamethasone or in comparable doses with other glucocorticoids.
• Treatment with any investigational agents within 5 half-lives of the agent in question or, if the half-life is unknown, within 28 days of enrollment.
• Pregnant or lactating females.
• Prior history of malignancy within 3 years of enrollment other than basal or squamous cell carcinoma of the skin, cervical intra-epithelial neoplasia, in situ carcinoma of the breast, or prostate cancer treated with surgery or RT with a prostate specific antigen of <0.01 ng/mL.
• Patients with active autoimmune diseases within 2 years of enrollment into the study including, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome, Wegener's granulomatosis, ulcerative colitis, Crohn's disease, myasthenia gravis, Graves' disease, or uveitis except for psoriasis not requiring systemic therapy, vitiligo or alopecia areata, or hypothyroidism; if an autoimmune condition has been clinically silent for 12 months or greater, the patient may be eligible for enrollment.
• Patients on immunosuppressive therapies; the use of topical, inhalational, ophthalmologic or intra articular glucocorticoids, or the use of physiologic replacement doses of glucocorticoids are permitted.
• Patients with primary immunodeficiency diseases.
• Patients with significant bleeding in the preceding 6 months or with known coagulopathies.
• History of abdominal fistula, intestinal perforation, or intra-abdominal abscess in the preceding 12 months.

• Positive serology for human immunodeficiency virus (HIV) infection, active hepatitis B*, or untreated hepatitis C; patients who have completed a course of anti-viral treatment for hepatitis C are eligible.

  o *In cases of negative results for HepB surface antigen with positive HepB core antibody, HBV DNA testing is required.

• Patient has a medical history of frequent ventricular ectopy, e.g., non-sustained ventricular tachycardia (VT).
• Significant cardiovascular disease, including New York Hospital Association Class III or IV congestive heart failure, myocardial infarction within 6 months of enrollment, unstable angina, poorly controlled cardiac arrhythmias, or stroke within the preceding 6 months.
• Any other uncontrolled inter current medical condition, including systemic fungal, bacterial, or viral infection; uncontrolled hypertension; diabetes mellitus; or chronic obstructive pulmonary disease requiring 2 or more hospitalizations in the preceding 12 months.
• Any psychiatric condition, substance abuse disorder, or social situation that would interfere with a patient's cooperation with the requirements of the study.
• Known sensitivity to Bev or any of the components of DSP-7888 Dosing Emulsion.
• 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.)
• Patient has dyspnea at rest (CTCAE ≥ Grade 3) or has required supplemental oxygen within 2 weeks of study enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: DSP-7888 Dosing Emulsion plus Bevacizumab	Drug: DSP-7888 Dosing Emulsion; DSP-7888 Dosing Emulsion will be administered i.d. every 7 ± 1 day for Doses 1 to 5, every 14 ± 3 days for Doses 6 to 15, and every 28 ± 7 days for Doses 16 and above.; Other Names: adegramotide and nelatimotide; Drug: Bevacizumab; Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.; Other Names: Avastin
Active Comparator: Arm 2: Bevacizumab	Drug: Bevacizumab; Bevacizumab will be administered intravenously every 14 ± 3 days at 10 mg/kg.; Other Names: Avastin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Who Experienced a Dose-limiting Toxicity	The number of participants with dose-limiting toxicity (DLT) who were enrolled into Part 1 - the safety set.	Dose-limiting toxicity will be evaluated and applied from Day 1 through Day 29
Overall Survival (OS) of Patients With Recurrent or Progressive Glioblastoma Multiforme (GBM) Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone	The effect of DSP-7888 Dosing Emulsion plus BEV versus BEV alone on the OS of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy.	4 weeks after the patient has been off study treatment, every 3 months thereafter until death, the study closes, up to 24 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS) of Patients With Recurrent or Progressive Glioblastoma Multiforme (GBM) Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone at 12 Months	The effect of DSP-7888 dosing emulsion plus BEV versus BEV alone on the OS of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy.	12 months
Progression Free Survival (PFS) of Patients With Recurrent or Progressive GBM	The effect of DSP-7888 dosing emulsion plus Bevacizumab (BEV) versus BEV alone on the Progression Free Survival (PFS) of patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy. PFS is defined as the interval between randomization and progression or death from any cause any cause as determined by the central radiology body.	The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause, up to 24 months
Progression Free Survival (PFS) Rate in Patients With Recurrent or Progressive GBM at 6 Months	The effect of DSP-7888 dosing emulsion plus Bevacizumab (BEV) versus BEV alone on the Progression Free Survival (PFS) rate in patients with recurrent or progressive GBM following treatment with first line therapy consisting of surgery and radiation with or without chemotherapy. PFS is defined as the interval between randomization date and progression or death from any cause as determined by the central radiology body. The percentage of patients who achieved PFS at 6 months are summarized.	The time from the date of first treatment to the date of first documentation of disease progression or death due to any cause at 6 months
The Effect of DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone on the Response Rate of Patients With Recurrent or Progressive GBM	Assessment of the objective response rate (ORR) of DSP-7888 dosing emulsion plus BEV versus BEV alone in patients with recurrent or progressive GBM. The response rate is defined as the percentage of patients exhibiting a response (complete response [CR] plus partial response [PR]) based on the Modified Response Assessment in Neuro-Oncology (RANO) criteria as determined by the central radiology body.	From the date of first treatment, every 8 weeks, until the date of first documented objective disease progression, up to 24 months
Duration of Response in Patients With Recurrent or Progressive GBM Treated With DSP-7888 Dosing Emulsion Plus Bevacizumab (BEV) Versus BEV Alone	The effect of DSP-7888 dosing emulsion plus BEV versus BEV alone on the duration of response of patients with recurrent or progressive GBM. The duration of response is defined as the interval between first documented oncological response and progression of disease or death from any cause.	From the date of first treatment up to 24 months
Number of Participants With Adverse Events and Serious Adverse Events	Assessment of safety of DSP7888 dosing emulsion plus Bevacizumab (BEV) versus BEV alone in patients with recurrent or progressive GBM	The time from the date of first treatment, while the patient is on treatment, and for 30 days after stopping therapy, an average of 4 months

Collaborators and Investigators

• Sponsor: Sumitomo Pharma America, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2017
• Primary Completion (Actual): August 30, 2021
• Study Completion (Actual): August 30, 2021

Study Registration Dates

• First Submitted: May 9, 2017
• First Submitted That Met QC Criteria: May 9, 2017
• First Posted (Actual): May 11, 2017

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Glioma; Cancer Vaccines; Neoplasms; Brain Tumor; Bevacizumab; Brain Cancer; Astrocytoma; Glioblastoma (GBM); Wilms Tumor 1 (WT1)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: BBI-DSP7888-201G

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No