Clinical Trials /

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

NCT03311334

Description:

This is a Phase 1b/2, open-label, multicenter study of DSP-7888 in combination with checkpoint inhibitors (nivolumab or pembrolizumab) in adult patients with solid tumors, that consists of 2 parts: dose search part of the study (Phase 1b) and the dose expansion part of the study (Phase 2). In Phase 1b of this study there will be 2 arms: Arm 1 and Arm 2. In Arm 1, there will be 6 to 12 patients who will be dosed with DSP-7888 and nivolumab and in Arm 2 there will be 6 to 12 patients who will be dosed with DSP-7888 and pembrolizumab. Once the recommended dose is determined in Phase 1b, platinum-resistant ovarian cancer (PROC) patients will be enrolled in Phase 2 of the study with DSP-7888, exploring the combination with pembrolizumab (Arm 2). In Phase 2, approximately 40 patients with PROC will be initially enrolled.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Cervical Carcinoma
  • Colorectal Carcinoma
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Hepatocellular Carcinoma
  • High Grade Fallopian Tube Serous Adenocarcinoma
  • High Grade Ovarian Serous Adenocarcinoma
  • Malignant Solid Tumor
  • Melanoma
  • Non-Small Cell Lung Carcinoma
  • Primary Peritoneal Serous Adenocarcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

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

Conditions

  • Neoplasms
  • Melanoma
  • Non Small Cell Lung Cancer (NSCLC)
  • Head and Neck Squamous Cell Carcinoma (HNSCC)
  • Renal Cell Carcinoma (RCC)
  • Urothelial Neoplasm
  • Hepatocellular Carcinoma (HCC)
  • Microsatellite Instability-high or Mismatch Repair Deficient (MSI-H/dMMR)
  • Colorectal Cancer
  • Gastroesophageal Junction Adenocarcinoma
  • Gastric Cancer
  • Cervical Cancer
  • Primary Peritoneal Cancer
  • Platinum-resistant Ovarian Cancer (PROC)
  • Serous Epithelial Ovarian Cancer
  • Fallopian Tube Cancer

Interventions

DrugSynonymsArms
DSP-7888 Dosing Emulsionadegramotide and nelatimotideDSP-7888 in combination with Nivolumab
NivolumabOpdivoDSP-7888 in combination with Nivolumab
PembrolizumabKeytrudaDSP-7888 in combination with Pembrolizumab

Purpose

This is a Phase 1b/2, open-label, multicenter study of DSP-7888 in combination with checkpoint inhibitors (nivolumab or pembrolizumab) in adult patients with solid tumors, that consists of 2 parts: dose search part of the study (Phase 1b) and the dose expansion part of the study (Phase 2). In Phase 1b of this study there will be 2 arms: Arm 1 and Arm 2. In Arm 1, there will be 6 to 12 patients who will be dosed with DSP-7888 and nivolumab and in Arm 2 there will be 6 to 12 patients who will be dosed with DSP-7888 and pembrolizumab. Once the recommended dose is determined in Phase 1b, platinum-resistant ovarian cancer (PROC) patients will be enrolled in Phase 2 of the study with DSP-7888, exploring the combination with pembrolizumab (Arm 2). In Phase 2, approximately 40 patients with PROC will be initially enrolled.

Trial Arms

NameTypeDescriptionInterventions
DSP-7888 in combination with NivolumabExperimental
  • DSP-7888 Dosing Emulsion
  • Nivolumab
DSP-7888 in combination with PembrolizumabExperimental
  • DSP-7888 Dosing Emulsion
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria Phase 1b:

        Patients must fulfill each of the following requirements:

          1. A histologically or cytologically confirmed cancer that is metastatic and is approved
             to be treated with nivolumab or pembrolizumab with the following origins:

               -  Nivolumab: unresectable or metastatic melanoma, metastatic NSCLC, advanced RCC,
                  recurrent or metastatic squamous cell carcinoma of the head and neck, locally
                  advanced or metastatic urothelial carcinoma, hepatocellular carcinoma, MSI-H/dMMR
                  colorectal cancer

               -  Pembrolizumab: unresectable or metastatic melanoma, metastatic NSCLC, recurrent
                  or metastatic squamous cell carcinoma of the head and neck, locally advanced or
                  metastatic urothelial carcinoma, unresectable or metastatic MSI-H/dMMR solid
                  tumors, recurrent locally advanced or metastatic gastric cancer or
                  gastroesophageal junction adenocarcinoma, recurrent or metastatic cervical cancer

             In addition, the following requirements must be fulfilled:

               1. Patients must not be considered eligible for a potentially curative resection.

               2. Patients who are eligible for PD-1 therapy based on either criterion (i) or (ii)
                  below:

             (i) Patients progressed on their prior treatment before initiating treatment on
             current study, OR (ii) Patients who are currently being treated with nivolumab or
             pembrolizumab 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.

          2. Patients must be positive for at least 1 of the following human leukocyte antigens:

               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. Patients must be able to provide archival tumor tissue with sufficient tumor tissue,
             or patients must consent to undergo tumor biopsy to acquire sufficient tissue before
             first administration of study.

          6. Females of childbearing potential must have a negative serum pregnancy test.

          7. Male or female patients 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 patients 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. Patients must be willing to provide a signed and dated ICF.

        Exclusion Criteria Phase 1b:

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

          1. Anticancer chemotherapy (including molecular targeted drugs), immunotherapy,
             radiotherapy, or investigational agents within 4 weeks of the first dose of DSP 7888.
             This exclusion is not applicable to patients who meet the inclusion criterion #1b
             (ii).

          2. Major surgery within 4 weeks prior to study treatment.

          3. Patients who have received a live vaccine within 4 weeks prior to the first dose.

          4. Any known, untreated brain metastases; 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 2 weeks prior to the first dose of study
             drug.

          5. Patients who have multifocal glioblastoma.

          6. Pregnant or breastfeeding.

          7. Patients who have an active autoimmune disease requiring immunosuppression > 5 mg/day
             prednisone or equivalent

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

          8. Patients who have interstitial lung disease or active, non-infectious pneumonitis.

          9. Known hypersensitivity to a component of protocol therapy:

               1. Patients with known hypersensitivity to any of the components of DSP-7888 Dosing
                  Emulsion.

               2. Patients with known hypersensitivity to nivolumab or pembrolizumab are excluded
                  from receiving combination therapy that includes the agent to which they are
                  hypersensitive.

         10. 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.

         11. Patients 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 patient has been disease free for ≥ 2 years that,
             in the opinion of the Investigator and medical monitor for the Sponsor, will not
             affect patient outcome in the setting of the current diagnosis.

         12. Patients who have 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.)

         13. Patients who have a medical history of frequent or sustained ventricular ectopy.

         14. Patients who have, 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.

         15. Known history of human immunodeficiency virus (HIV) infection, active hepatitis B, or
             untreated hepatitis C.

             Note: Patients who have completed a course of antiviral treatment for hepatitis C and
             are cured are eligible. In cases of negative results, hepatitis B surface antigen with
             positive hepatitis B core antibody, and hepatitis B virus DNA testing are required.

         16. Patients who have 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.

        Inclusion Criteria Phase 2:

        Patients eligible for inclusion must meet all of the following criteria:

          1. 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.

          2. Patients 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. Patients must have histologically diagnosed high-grade (Grade 2 or 3) serous
             epithelial ovarian, fallopian tube, or primary peritoneal cancer.

          4. 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.

          5. 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;

               1. 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.)

               2. Neoadjuvant or adjuvant systemic therapy counts as one line of therapy
                  respectively

               3. Patients must have received at least one platinum-based therapy

          6. Patients must have progression disease after last therapy and have measurable disease
             according to RECIST (v1.1).

          7. Patients must have an ECOG performance status of 0 or 1.

          8. Patients must have adequate organ function, defined as follows:

             Hematological:

               1. Absolute neutrophil count (ANC) ≥ 1,500/μL (without granulocyte-colony
                  stimulating factor (G-CSF))

               2. Platelets ≥ 100,000/μL (without transfusion)

               3. Hemoglobin ≥ 9.0 g/dL (without transfusion)

             Renal:

             a. Serum Creatinine OR estimated glomerular filtration rate using the Cockcroft-Gault
             equation ≤ 1.5 × the upper limit of normal (ULN) OR 40 mL/min using the
             Cockcroft-Gault equation for patients with creatinine levels > 1.5 × ULN

             Hepatic:

               1. Serum total bilirubin ≤ 1.5 ULN

               2. Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN OR ≤
                  5 × ULN for patients with liver metastases

             Cardiac:

               1. Multigated acquisition (MUGA) scan or echocardiogram with left ventricular
                  ejection fraction (LVEF) ≥ 40%.

               2. QTcF (QT corrected based on Fridericia's equation) interval < 480 msec

             Coagulation:

               1. International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 × ULN

               2. Activated Partial Thromboplastin Time (aPTT) or Partial Thromboplastin Time (PTT)
                  ≤ 1.5 × ULN

          9. 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).

         10. Patients of childbearing potential must have a negative serum or urine pregnancy test
             at screening.

         11. Patients must be either postmenopausal, free from menses > 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.

         12. Life expectancy ≥ 3 months.

        Exclusion Criteria Phase 2:

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

          1. Primary platinum refractory patients defined as patients who experienced disease
             progression during the treatment with first-line platinum therapy.

          2. 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.

          3. 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).

          4. Patients who have received prior treatment with any other Wilms Tumor 1 (WT1)-related
             agents including peptide vaccine, dendric cell vaccine, and gene therapy.

          5. Patients who have received treatment for ovarian cancer within the following time
             frame prior to the first dose of the study

               1. Cytotoxic chemotherapy, hormonal therapy; ≤ 3 weeks

               2. Targeted therapy except for monoclonal antibody; ≤ 3 weeks

               3. Immune therapy, biologic therapy (e.g. antibodies); ≤ 4 weeks

               4. Other investigational agents: ≤ 4 weeks

               5. Radiation therapy (except for localized radiotherapy for analgesic purpose) ≤ 4
                  weeks

               6. Radiation therapy (localized radiotherapy for analgesic purpose) ≤ 1 week

               7. Major surgery regardless of reason ≤ 4 weeks.

          6. Patients who have received a live vaccine within 4 weeks prior to the first dose.

          7. Any known additional malignancy that is progressing or requires active treatment with
             the exception of:

               1. curatively treated basal cell or squamous cell carcinoma of skin

               2. curatively treated superficial bladder cancer, carcinoma in situ of the cervix,

               3. 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.

          8. Patients who have not recovered to < CTCAE Grade 2 or baseline from toxic effect (with
             exception of alopecia) of prior cancer therapy.

          9. 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.

         10. 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.

         11. Patients who have a known history of bacillus tuberculosis (TB).

         12. 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 arrythmia, congestive heart
                  failure, or cardiomyopathy

               -  Unstable angina pectoris ≤ 6 months before study participation

               -  Myocardial infarction or stroke ≤ 6 months before study participation

         13. Patients who have an interstitial lung disease or a history of pneumonitis that
             required oral or intravenous glucocorticoids to assist with management.

         14. Patients with infections that have required treatment with systemic antibiotics within
             7 days prior to the first dose of protocol therapy.

         15. 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.

         16. 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.

         17. Patients who are pregnant or breastfeeding.

         18. Patients who have known hypersensitivity to DSP-7888, pembrolizumab, their components,
             or their excipients.

         19. Patient has dyspnea at rest (CTCAE ≥ Grade 3) or has 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:Phase Ib: Determination of the safety and tolerability of DSP-7888 Dosing Emulsion given intradermally with a checkpoint inhibitor (Nivolumab or Pembrolizumab) in adult patients with advanced solid tumors by assessing dose-limiting toxicities (DLTs).
Time Frame:6 weeks
Safety Issue:
Description:Defined as the proportion of patients who have achieved confirmed CR or PR by RECIST v1.1 based on investigator assessment.

Secondary Outcome Measures

Measure:Phase Ib: Objective response rate (ORR)
Time Frame:12 months
Safety Issue:
Description:Defined as the proportion of patients who have achieved confirmed complete response (CR) or partial response (PR) evaluated using RECIST v1.1 and iRECIST.
Measure:Phase Ib: Disease control rate (DCR)
Time Frame:6 months
Safety Issue:
Description:Defined as the percentage of patients who have achieved best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD) per RECIST v1.1 and iRECIST.
Measure:Phase Ib: Duration of response (DOR)
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 and iRECIST or death by any cause.
Measure:Phase Ib: Progression-free survival (PFS)
Time Frame:12 months
Safety Issue:
Description:Defined as the time from first dose of study treatment to the earlier date of assessment of progression by RECIST v1.1 and iRECIST or death by any cause.
Measure:Phase Ib: 6-month PFS
Time Frame:6 months
Safety Issue:
Description:Defined as the proportion of patients who neither progressed by RECIST v1.1 and iRECIST nor died before six months (24 weeks) from the first study treatment.
Measure:Phase Ib: Overall survival (OS)
Time Frame:12 months
Safety Issue:
Description:Defined as the time from the date of first dose of study treatment to the date of death by any cause.
Measure:Phase II: DOR
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as the time from the first documentation of a response (CR or PR) until time of first documentation of disease progression by RECIST v1.1 or death by any cause.
Measure:Phase II: DCR
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as the percentage of patients who have achieved BOR of CR, PR, or SD per RECIST v1.1.
Measure:Phase II: PFS
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression by RECIST v1.1 or death by any cause.
Measure:Phase II: 6 month PFS
Time Frame:6 months
Safety Issue:
Description:Defined as the proportion of patients who neither progressed by RECIST v1.1 nor died before 6 months (24 weeks) from the first study treatment.
Measure:Phase II: OS
Time Frame:Up to 48 months
Safety Issue:
Description:Defined as the time from the date of first dose of study treatment to the date of death by any cause.
Measure:Phase II: Immune objective response rate (iORR)
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as the proportion of patients who have achieved confirmed immune complete response (iCR) or immune partial response (iPR), evaluated using iRECIST based on investigator assessment.
Measure:Phase II: Immune disease control rate (iDCR)
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as the percentage of patients who have achieved BOR of iCR, iPR, or iSD per iRECIST.
Measure:Phase II: Immune progression-free survival (iPFS)
Time Frame:Up to 24 months
Safety Issue:
Description:Defined as the time from the date of the first dose of study treatment to the earlier date of assessment of progression by iRECIST or death by any cause.
Measure:Phase II: Evaluation of the safety and tolerability of DSP-7888 Dosing Emulsion administered with pembrolizumab.
Time Frame:Up to 24 months
Safety Issue:
Description:Determined by frequency and intensity of adverse events (AE) using Common Terminology Criteria for Adverse Events (CTCAE) ver 4.03.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Boston Biomedical, Inc

Trial Keywords

  • DSP-7888
  • nivolumab
  • pembrolizumab
  • immune checkpoint inhibitor
  • cancer vaccine
  • WT1
  • ICI
  • Wilms Tumor 1

Last Updated

January 17, 2020