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A Study of DSP-7888 Dosing Emulsion in Combination With Immune Checkpoint Inhibitors in Adult Subjects With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT03311334
Recruitment Status : Recruiting
First Posted : October 17, 2017
Last Update Posted : September 14, 2018
Sponsor:
Information provided by (Responsible Party):
Boston Biomedical, Inc

Brief Summary:
This is a Phase 1, open label, multi-center study of DSP-7888 Dosing Emulsion, administered intradermally in combination with checkpoint inhibitors (Nivolumab or Atezolizumab) in adult subjects with solid tumors, including advanced melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), renal cell carcinoma (RCC), and urothelial cancer that consists of two parts: dose search (Part 1) and expansion (Part 2).

Condition or disease Intervention/treatment Phase
Neoplasms Melanoma Non Small Cell Lung Cancer Head and Neck Squamous Cell Carcinoma Renal Cell Carcinoma Urothelial Neoplasm Drug: DSP-7888 Dosing Emulsion Drug: Nivolumab Drug: Atezolizumab Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Multicenter, Open-Label Study of DSP 7888 Dosing Emulsion in Combination With Immune Checkpoint Inhibitors Nivolumab or Atezolizumab in Adult Subjects With Advanced Solid Tumors
Actual Study Start Date : December 14, 2017
Estimated Primary Completion Date : October 2018
Estimated Study Completion Date : November 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: DSP-7888 in combination with Nivolumab Drug: DSP-7888 Dosing Emulsion
DSP-7888 Dosing Emulsion will be administered i.d. every 7 days until cycle 2, and then every 14 days for combination with Nivolumab arm, and every 21 days for Atezolizumab arm.
Other Name: adegramotide and nelatimotide

Drug: Nivolumab
Nivolumab will be administered in the approved dose and schedule starting on Day 1 of the study.
Other Name: Opdivo

Experimental: DSP-7888 in combination with Atezolizumab Drug: DSP-7888 Dosing Emulsion
DSP-7888 Dosing Emulsion will be administered i.d. every 7 days until cycle 2, and then every 14 days for combination with Nivolumab arm, and every 21 days for Atezolizumab arm.
Other Name: adegramotide and nelatimotide

Drug: Atezolizumab
Atezolizumab will be administered in the approved dose and schedule starting on Day 1 of the study.
Other Name: Tecentriq




Primary Outcome Measures :
  1. Determination of the safety and tolerability of DSP-7888 Dosing Emulsion given intradermally with a checkpoint inhibitor (Nivolumab or Atezolizumab) in adult subjects with advanced solid tumors by assessing dose-limiting toxicities (DLTs) [ Time Frame: 6 weeks ]
  2. Determination of the Recommended Phase 2 Dose (RP2D) by assessing dose-limiting toxicities (DLTs) [ Time Frame: 6 weeks ]

Secondary Outcome Measures :
  1. Duration of response by RECIST [ Time Frame: 6 months ]
    Defined as the time from first documentation of response until the time of first documentation of disease progression by RECIST v1.1.

  2. Duration of response by iRECIST [ Time Frame: 6 months ]
    Defined as the time from first documentation of response until the time of first documentation of disease progression by iRECIST.

  3. Disease control rate by RECIST [ Time Frame: 6 months ]
    Defined as the percentage of subjects who have achieved complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1.

  4. Disease control rate by iRECIST [ Time Frame: 6 months ]
    Defined as the percentage of subjects who have achieved complete response (CR), partial response (PR), or stable disease (SD) per iRECIST.

  5. 12-month survival [ Time Frame: 12 months ]
    Defined as the proportion of subjects alive 12 months from first dose.

  6. 6-month Progression-free survival (PFS) [ Time Frame: 6 months ]
    Defined as the proportion of subjects alive at 6 from the date of first dose and without progressive neoplastic disease.

  7. PFS by RECIST [ Time Frame: 12 months ]
    Defined as the time from first dose to the earlier date of assessment of progression or death by any cause in the absence of progression by RECIST v1.1.

  8. PFS by iRECIST [ Time Frame: 12 months ]
    Defined as the time from first dose to the earlier date of assessment of progression or death by any cause in the absence of progression by iRECIST.

  9. Overall survival [ Time Frame: 12 months ]
    Measured from the date of first dose to the date of death by any cause.


Other Outcome Measures:
  1. Expression levels of Wilms Tumor 1 (WT1) and PD-L1 on tumor tissues at baseline and at the end of treatment [ Time Frame: 6 months ]
  2. Ratio of WT1-specific cytotoxic T lymphocyte (CTL) in CD8+ cells in peripheral blood mononuclear cells (PBMCs) during the treatment [ Time Frame: 6 months ]
  3. Number of various T cells containing tumor-infiltrating lymphocytes (TIL) in tumor tissues at baseline and during/post-treatment samples [ Time Frame: 6 months ]
  4. Expression levels of WT1 and PD-L1 on tumor tissues at baseline and at the end of treatment [ Time Frame: 6 months ]
  5. Mutation status in tumor tissues at baseline [ Time Frame: 6 months ]
    Evaluated by the count of genetic mutation in the region encoding tumor-related genes.

  6. Microsatellite instability in tumor tissues at baseline [ Time Frame: 6 months ]
    Evaluated and categorized into MSI-H/MSI-L/MSS using a microsatellite instability assay kit.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Subjects must fulfil all of the following requirements:

  1. A histologically or cytologically confirmed cancer that is metastatic and is approved to be treated with Nivolumab or Atezolizumab with the following origins: melanoma, NSCLC, HNSCC, RCC, and urothelial cancer, as well as the following:

    1. Subjects must not be considered eligible for a potentially curative resection.
    2. Subjects who are eligible for PD-1/PD-L1 therapy or who have exhausted all standard therapies for their disease except for immunotherapy.

      either c) or d)

    3. Subjects progressed on their prior treatment before initiating treatment on current study.

      Or

    4. Subjects, who are currently being treated with PD-1 or PD-L1 inhibitors Nivolumab or Atezolizumab and have achieved at least stable disease (SD), and who, in the judgment of their treating physicians, could benefit from the addition of DSP-7888 vaccine to improve or maintain their response.

    In expansion part only: All subjects who are candidates for immunotherapy including PD-1/PD-L1 inhibitors are eligible to enroll in the study. Subjects must have at least 1 target lesion based on RECIST criteria and other supporting disease specific evaluation criteria.

  2. Subjects must be positive for at least 1 of the following human leukocyte antigens (HLA):

    1. HLA-A*02:01
    2. HLA-A*02:06
    3. HLA-A*24:02
  3. ≥ 18 years of age.
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  5. Either archival tumor tissue must be available or subject must consent to undergo a tumor biopsy before administration of first dose.
  6. Females of childbearing potential must have a negative serum pregnancy test.
  7. Male or female subjects of child-producing potential must agree to use contraception or use prevention of pregnancy measures (true abstinence) during the study and for 150 days after the last dose.
  8. Total bilirubin of ≤ 2.0 mg/dL (≤ 3.0 mg/dL for subjects with known Gilbert's syndrome)
  9. Aspartate aminotransferase (AST) ≤ 3.0 × the upper limit of normal (ULN) or < 5 × ULN if considered to be due to liver metastases.
  10. Alanine transaminase (ALT) ≤ 3.0 × the upper limit of normal (ULN) or < 5 × ULN if considered to be due to liver metastases.
  11. Glomerular Filtration Rate > 40 mL/min.
  12. Multigated acquisition (MUGA) scan or echocardiogram with left ventricular ejection fraction (LVEF) > 40%.
  13. Life expectancy ≥ 3 months.
  14. Subjects must be willing to provide a personally signed and dated informed consent document.

Exclusion Criteria

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

  1. Anticancer chemotherapy (including molecular targeted drugs), immunotherapy, or investigational agents within 7 days of the first dose of DSP-7888; radiotherapy within 4 weeks of the first dose of DSP-7888. Subjects may begin DSP-7888 on a date determined by the Investigator and medical monitor for the Sponsor provided that all treatment related adverse events (AEs) have resolved or have been deemed irreversible. This exclusion is not applied to subjects who meet the inclusion criterion 1d.
  2. In expansion part only: Subjects progressed on their prior checkpoint inhibitors (PD-1/PD-L1) treatment before initiating treatment on current study.
  3. Major surgery within 4 weeks prior to study treatment.
  4. Subject has received a live vaccine within 30 days prior to the first dose.
  5. Any known, untreated brain metastases. Subjects 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. Subjects must have no clinical symptoms from brain metastases and not have required systemic corticosteroids > 10 mg/day prednisone or equivalent for at least 2 weeks prior to the first dose of study drug.
  6. Subject has multifocal glioblastoma.
  7. Pregnant or breastfeeding.
  8. Subject has an active autoimmune disease requiring immunosuppression with the exception of subjects with isolated vitiligo, resolved childhood asthma or atopic dermatitis, controlled hypoadrenalism or hypopituitarism, and euthyroid subjects with a history of Grave's disease.

    a. Subjects with controlled hyperthyroidism must be negative for thyroglobulin and thyroid peroxidase antibodies and thyroid stimulating immunoglobulin prior to study drug administration.

  9. Subject has interstitial lung disease or active, non-infectious pneumonitis.
  10. Known hypersensitivity to a component of protocol therapy.

    1. Subjects with known hypersensitivity to any of the components of DSP-7888 Dosing Emulsion.
    2. Subjects with known hypersensitivity to Nivolumab or Atezolizumab are excluded from receiving combination therapy that includes the agent to which they are hypersensitive.
  11. Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, clinically significant non-healing or healing wounds, symptomatic congestive heart failure, unstable angina pectoris, severe and/or uncontrolled cardiac arrhythmia, significant pulmonary disease, uncontrolled infection or psychiatric illness/social situations that would limit compliance with study requirements.
  12. Subjects with a history of another primary cancer with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; c) localized prostate cancer not requiring systemic therapy; and d) any another cancer from which the subject has been disease free for ≥ 2 years that, in the opinion of the Investigator and medical monitor for the Sponsor, will not affect subject outcome in the setting of the current diagnosis.
  13. 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.)
  14. Subject has a medical history of frequent or sustained ventricular ectopy.
  15. Subject 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.
  16. Known history of 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.
  17. Subject has baseline signs and symptoms consistent with clinically significant, decreased pulmonary function: (1) blood saturation oxygen level (SpO2) < 90% at rest on room air; (2) dyspnea at rest or required supplemental oxygen within 2 weeks of study enrollment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03311334


Contacts
Contact: Boston Biomedical 617-674-6800 info@bostonbiomedical.com

Locations
United States, Illinois
Decatur Memorial Hospital Recruiting
Decatur, Illinois, United States, 62526
United States, Indiana
Horizon Oncology Research Recruiting
Lafayette, Indiana, United States, 47905
United States, Kentucky
Norton Healthcare Inc. Recruiting
Louisville, Kentucky, United States, 40202
United States, Montana
St Vincent Frontier Cancer Center Recruiting
Billings, Montana, United States, 59102
United States, Ohio
Gabrail Cancer Center Research Withdrawn
Canton, Ohio, United States, 44718
United States, Texas
Texas Oncology (Baylor Charles A Sammons Cancer Center) Recruiting
Dallas, Texas, United States, 75246
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Boston Biomedical, Inc

Responsible Party: Boston Biomedical, Inc
ClinicalTrials.gov Identifier: NCT03311334     History of Changes
Other Study ID Numbers: BBI-DSP7888-102CI
First Posted: October 17, 2017    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Boston Biomedical, Inc:
DSP-7888
nivolumab
atezolizumab
immune checkpoint inhibitor
cancer vaccine
Wilms Tumor 1
ICI

Additional relevant MeSH terms:
Carcinoma
Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Carcinoma, Renal Cell
Head and Neck Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Squamous Cell
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Nivolumab
Atezolizumab
Antibodies, Monoclonal
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs