Clinical Trials /

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

NCT03311334

Description:

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).

Related Conditions:
  • Head and Neck Squamous Cell Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: BBI-DSP7888-102CI
  • NCT ID: NCT03311334

Conditions

  • Neoplasms
  • Melanoma
  • Non Small Cell Lung Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Renal Cell Carcinoma
  • Urothelial Neoplasm

Interventions

DrugSynonymsArms
DSP-7888 Dosing Emulsionadegramotide and nelatimotideDSP-7888 in combination with Nivolumab
NivolumabOpdivoDSP-7888 in combination with Nivolumab
AtezolizumabTecentriqDSP-7888 in combination with Atezolizumab

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
DSP-7888 in combination with NivolumabExperimental
  • DSP-7888 Dosing Emulsion
  • Nivolumab
DSP-7888 in combination with AtezolizumabExperimental
  • DSP-7888 Dosing Emulsion
  • Atezolizumab

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Duration of response by RECIST
Time Frame:6 months
Safety Issue:
Description:Defined as the time from first documentation of response until the time of first documentation of disease progression by RECIST v1.1.
Measure:Duration of response by iRECIST
Time Frame:6 months
Safety Issue:
Description:Defined as the time from first documentation of response until the time of first documentation of disease progression by iRECIST.
Measure:Disease control rate by RECIST
Time Frame:6 months
Safety Issue:
Description:Defined as the percentage of subjects who have achieved complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1.
Measure:Disease control rate by iRECIST
Time Frame:6 months
Safety Issue:
Description:Defined as the percentage of subjects who have achieved complete response (CR), partial response (PR), or stable disease (SD) per iRECIST.
Measure:12-month survival
Time Frame:12 months
Safety Issue:
Description:Defined as the proportion of subjects alive 12 months from first dose.
Measure:6-month Progression-free survival (PFS)
Time Frame:6 months
Safety Issue:
Description:Defined as the proportion of subjects alive at 6 from the date of first dose and without progressive neoplastic disease.
Measure:PFS by RECIST
Time Frame:12 months
Safety Issue:
Description: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.
Measure:PFS by iRECIST
Time Frame:12 months
Safety Issue:
Description: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.
Measure:Overall survival
Time Frame:12 months
Safety Issue:
Description:Measured from the date of first dose to the date of death by any cause.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Boston Biomedical, Inc

Trial Keywords

  • DSP-7888
  • nivolumab
  • atezolizumab
  • immune checkpoint inhibitor
  • cancer vaccine
  • Wilms Tumor 1
  • ICI

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