| Eligibility |
Inclusion Criteria Phase 1b:
Patients must fulfill each of the following requirements:
1. Phase 1b Dose Search Part Only: 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 Dosing
Emulsion vaccine to improve or maintain their response.
Phase 1b Enrichment Cohort Only: Patients with locally advanced or metastatic RCC or
urothelial carcinoma who have experienced disease progression per iRECIST (iCPD)
during or within 3 months of last dose of the most recent prior anti-PD-1/ PD-L1-based
treatment
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
4. HLA-A*03:01
5. HLA-B*15:01
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
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
Dosing Emulsion
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 > 10
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 > 10 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,
uncontrolled bacterial, viral, or fungal infections requiring systemic therapy;
clinically significant non-healing or healing wounds; symptomatic congestive heart
failure; unstable angina pectoris; severe and/or uncontrolled cardiac arrhythmia;
significant pulmonary disease; 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
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
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):
a. HLA-A*02:01 b. HLA-A*02:06 c. HLA-A*24:02 d. HLA-A*03:01 e. HLA-B*15:01
3. Patients must have histologically diagnosed ovarian, fallopian tube, or primary
peritoneal cancer with predominantly high-grade (Grade 2 or 3) serous epithelial features
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 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 and adjuvant systemic therapy will be counted 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:
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 6 months after the last dose of study
treatment 12. Life expectancy = 3 months 13. Patients who had stayed on the last
treatment for at least 12 weeks without any evidence of progression
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 > 10 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 and/or neuropathy) of prior cancer therapy.
9. Patients who have an active autoimmune disease requiring systemic immunosuppression in
excess of physiologic maintenance dose of corticosteroids (> 10 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
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 active, uncontrolled bacterial, viral, or fungal infections, requiring
systemic 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 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
20. Patients with history of bowel obstruction related to underlying disease within 3
months prior to the first dose of study treatment
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