This is a Phase 1b/2, open-label, multicenter study of DSP-7888 Dosing Emulsion 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 Dosing
Emulsion and nivolumab and in Arm 2 there will be 6 to 12 patients who will be dosed with
DSP-7888 Dosing Emulsion and pembrolizumab. In addition, an enrichment cohort of a further 10
patients who have locally advanced or metastatic Renal Cell Carcinoma or Urothelial Cancer
with primary or acquired resistance to previous checkpoint inhibitors will be enrolled into
Phase 1b of the study to help evaluate the preliminary antitumor activity of DSP-7888 Dosing
Emulsion at the safe dose level identified in the dose-search part of the study, and will be
dosed with DSP-7888 Dosing Emulsion and nivolumab, or DSP-7888 Dosing Emulsion and
pembrolizumab, as per the investigator's preference. 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 Dosing Emulsion, exploring the combination with pembrolizumab (Arm
2). In Phase 2, approximately 40 patients with PROC will be initially enrolled. Approximately
80 patients in total will be enrolled in the study, if both groups in Phase 2 are enriched
with an additional 20 patients. This brings the total maximum study population to
approximately 104 patients. Patients in the enrichment cohort will not be replaced.
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
- 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
- Note: Only patients with locally advanced or metastatic RCC or urothelial
carcinoma are eligible for participation in the Phase 1b enrichment cohort.
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)
(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 Dosing
Emulsion vaccine to improve or maintain their response.
2. Patients must be positive for at least 1 of the following human leukocyte antigens:
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 6
months (for females and males alike) after the last dose.
8. Total bilirubin of ≤ 2.0 mg/dL (≤ 3.0 mg/dL for patients with known Gilbert's
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
Dosing Emulsion. 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
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
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
2. Patients with known hypersensitivity to nivolumab or pembrolizumab are excluded
from receiving combination therapy that includes the agent to which they are
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
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
3. Patients must have histologically diagnosed serous epithelial ovarian, fallopian tube,
or primary peritoneal cancer with predominantly high-grade (Grade 2 or 3) serous
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
5. Patients must have completed at least 1 but no more than 4 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
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:
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)
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
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
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
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
10. Patients of childbearing potential must have a negative serum or urine pregnancy test
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
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
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
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
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
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 Dosing Emulsion, 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.