Clinical trial NCT03311334
Conditions: Renal Cell Carcinoma (RCC) Urothelial Carcinoma Primary Peritoneal Cancer Platinum-resistant Ovarian Cancer (PROC) Serous Epithelial Ovarian Cancer Fallopian Tube Cancer
Keywords: DSP-7888 Nelatimotide Adegramotide immune checkpoint inhibitor cancer vaccine WT1 ICI Wilms Tumor 1 Ombipepimut-S nivolumab Opdivo pembrolizumab Keytruda Ovarian cancer Platinum-resistant ovarian cancer PROC Serous epithelial ovarian cancer High-grade serous epithelial ovarian cancer HGSOC Fallopian tube cancer FTC Peritoneal cancer Primary peritoneal cancer PPC Renal cell carcinoma Kidney cancer RCC Metastatic Renal Cell Carcinoma Metastatic RCC Metastatic kidney cancer Advanced Renal Cell Carcinoma Advanced RCC Advanced kidney cancer Urothelial carcinoma Bladder cancer Transitional cell carcinoma UC Metastatic urothelial carcinoma Metastatic transitional cell carcinoma Metastatic UC Advanced urothelial carcinoma Advanced UC Advanced transitional cell carcinoma
Sponsor: Sumitomo Pharma America, Inc.
Start date: 2017-12-14; Completion date: 2022-11-29
Enrollment: 47 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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 Phase 1b Enrichment Cohort) 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. At the safe, recommended dose 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; additional patients may be enrolled to further assess anti-tumor activities, but the total sample size will not exceed 60 patients. This brings the total maximum study population to approximately 84 patients.

Detailed description:

Arms: arm 1: None arm 2: None
Interventions: intervention 1: DSP-7888 Dosing Emulsion intervention 2: Nivolumab intervention 3: Pembrolizumab
Intervention descriptions: intervention 1: DSP-7888 Dosing Emulsion will be administered intradermally (ID) every 7 days until cycle 3, and then every 14 days for combination with Nivolumab arm or every 21 days for combination with Pembrolizumab arm. intervention 2: Nivolumab will be administered in the approved dose and schedule starting on Day 29 of the study. intervention 3: Pembrolizumab will be administered in the approved dose and schedule starting on Day 22 of the study.

Protocol documents:
Prot_000.pdf: 
1.
TITLE PAGE
DSP-7888 
BBI-DSP-7888-102CI 
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
Study Protocol Number: BBI-DSP-7888-102CI 
Study Medication Name: Nelatimotide and Adegramotide 
(Ombipepimut-S) 
(hereafter referred to as DSP-7888) Dosing 
Emulsion 
Developmental Phase: Phase 1b/2 
Indication: Advanced solid tumors: Phase 1b 
Platinum-Resistant Ovarian Cancer: Phase 2 
Sponsor: 
Contract Research Organization (CRO): 
Amendment 6.0 Date 22 Jul 2021 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of 
. Any unauthorized use or disclosure of such 
information without the prior written authorization of 
, 
is prohibited.


  
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SIGNATURE PAGE 
Sponsor’s Signatory: 
The protocol has been approved by 
 
 
 
Date 
 
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INVESTIGATOR’S AGREEMENT 
 
I have received and read the Investigator’s Brochure for DSP-7888. I have read the protocol for 
Study BBI-DSP-7888-102CI and agree to conduct the study as outlined. I agree to maintain the 
confidentiality of all information received or developed in connection with this protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Investigator 
 
 
 
 
 
 
 
 
Date 


 
 
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CONTACT INFORMATION 
Table 1: 
Contact Information 
Role in Study 
Name 
Address/Email &  
Telephone Number 
Clinical Study Leader 
 
 
 
 
 
 
Responsible Physician / 
24-Hour Emergency Contact: 
Phase 1 
 
  
 
 
 
 
  
Responsible Physician / 
24-Hour Emergency Contact: 
Phase 2 
 
 
 
 
 
 
 
Drug Safety Physician 
 
 
 
 
 
 
 
 
 


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2. 
SYNOPSIS 
Name of Sponsor/Company: 
 
Name of Investigational Product: 
Nelatimotide and Adegramotide (Ombipepimut-S) 
(hereafter referred to as DSP-7888) Dosing Emulsion 
Title of Study:   
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 
Study center(s): A multicenter study 
Studied period (years):  
Estimated date first patient enrolled: 21 Dec 2017 
Estimated date last patient completed: 30 Sep 2023 
Phase of development: 1b/2 
Objectives:  
Phase 1b 
Primary: To evaluate the safety and tolerability of, and to identify a recommended intradermal dose of 
DSP-7888 Dosing Emulsion in combination with nivolumab or pembrolizumab 
Secondary: To evaluate the preliminary antitumor activity 
Phase 2 
Primary: To evaluate the preliminary antitumor activity of DSP-7888 Dosing Emulsion administered 
with pembrolizumab in terms of the objective response rate (ORR) per Response Evaluation Criteria in 
Solid Tumors (RECIST) v1.1 in patients with platinum-resistant ovarian cancer (PROC) 
Secondary: To evaluate the preliminary clinical activity of DSP-7888 Dosing Emulsion in 
combination with pembrolizumab in terms of duration of response (DOR), disease control rate (DCR), 
progression-free survival (PFS), 6-month PFS Rate, and overall survival (OS) of DSP-7888 Dosing 
Emulsion administered in combination with pembrolizumab in PROC. To determine ORR, DCR and 
PFS per immune RECIST (iRECIST) of DSP-7888 Dosing Emulsion administered in combination 
with pembrolizumab in PROC and to evaluate the safety and tolerability of DSP-7888 Dosing 
Emulsion administered with pembrolizumab 
Study Design:  
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: Phase 1b (a dose search part and an enrichment part) and Phase 2 dose-expansion. In the 
Phase 1b part 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, a Phase 1b enrichment cohort of a further 10 patients, who have locally advanced or 
metastatic renal cell carcinoma (RCC) or urothelial cancer with primary or acquired resistance to 
previous checkpoint inhibitors, will be enrolled and will be dosed with DSP-7888 Dosing Emulsion 
and nivolumab, or DSP-7888 Dosing Emulsion and pembrolizumab, as per the investigator’s 
preference. The purpose of this Phase 1b enrichment cohort is to help evaluate the preliminary 


 
 
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antitumor activity of DSP-7888 Dosing Emulsion at the safe dose level identified in the Phase 1b 
dose-search part.  
Once the recommended dose is determined in the Phase 1b dose search part, PROC patients will be 
enrolled in the Phase 2 part of the study with DSP-7888 Dosing Emulsion, exploring the combination 
with pembrolizumab. In Phase 2, a total of approximately 40 patients with PROC will be enrolled. 
Additional patients may be enrolled to further assess anti-tumor activities in the subgroups of interest. 
However, the total sample size of Phase 2 part cannot exceed 60 patients. 
Phase 1b 
After providing written informed consent, patients will undergo screening assessments, which will 
include a careful review of each patient’s medical history. 
Patients will be administered doses of DSP-7888 Dosing Emulsion intradermally in both arms of the 
study (Arm 1 and Arm 2). Arm 1 will include patients with indications approved by the Health 
Authorities for treatment with nivolumab: advanced melanoma, non-small cell lung cancer (NSCLC), 
RCC, urothelial carcinoma, head and neck squamous cell carcinoma (HNSCC), hepatocellular 
carcinoma (HCC), and microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) 
colorectal cancer. Arm 2 will include patients with indications approved by the Health Authorities for 
treatment with pembrolizumab: melanoma, NSCLC, HNSCC, urothelial carcinoma, MSI-H/dMMR 
cancer, gastric cancer or gastroesophageal junction adenocarcinoma, and cervical cancer.  
In the Phase 1b dose search part of the study, during the Arm 1 induction phase (4 weeks), DSP-7888 
Dosing Emulsion will be administered once weekly for 4 weeks, with nivolumab administered every 
other week. In the subsequent Arm 1 maintenance phase, DSP-7888 Dosing Emulsion will be 
administered once every 2 weeks with nivolumab until a discontinuation criterion is met. During the 
Arm 2 induction phase (6 weeks), DSP-7888 Dosing Emulsion will be administered once weekly for 
6 weeks, with pembrolizumab administered once every 3 weeks. In the subsequent Arm 2 maintenance 
phase, DSP-7888 Dosing Emulsion will be administered once every 3 weeks with pembrolizumab until 
a discontinuation criterion is met. 
Both programmed cell death-1 (PD-1) inhibitors (nivolumab and pembrolizumab) will be administered 
in the approved dose and schedule starting on Day 1 of the study. Study sites will not be limited to any 
arm of the study, and each arm will investigate the recommended dose in parallel.  
Objective disease assessments will be performed according to RECIST (v1.1) and iRECIST, with the 
first assessment performed at the end of the dose-limiting toxicity (DLT) period (Cycle 3: at 4 weeks 
for nivolumab arm, at 6 weeks for pembrolizumab arm), and at Weeks 12, 18, and 24 after the first 
dose of DSP-7888 Dosing Emulsion. After that, objective disease assessments will occur every 
12 weeks until patient discontinuation from the study.  
The Phase 1b dose search part of the study is completed, and no further patients will be enrolled 
under the dosing regimen described above (this legacy dosing regimen is also depicted in 
Appendix 8). For patients enrolled under the Phase 1b enrichment part of the study, the dosing 
regimen described below will be followed per Amendment 5 of the protocol. 
The Phase 1b enrichment cohort (consisting of the additional 10 patients) will include patients with 
locally advanced or metastatic RCC or urothelial carcinoma who experienced disease progression per 
iRECIST (immune confirmed progressive disease [iCPD]) during or within 3 months of last dose of 
the most recent prior anti-PD-1/PD-L1-based treatment.  
Patients will be treated with the combination of DSP-7888 Dosing Emulsion and nivolumab, or 
DSP-7888 Dosing Emulsion and pembrolizumab, as per the treating physician’s choice.  


 
 
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The administration of DSP-7888 Dosing Emulsion and anti-PD-1 in the Phase 1b enrichment cohort 
will differ from that in the Phase 1b dose search part of the study, and will be staggered as follows:   
Arm 1 (Enrichment Cohort Only): DSP-7888 Dosing Emulsion + nivolumab combination: 
• 
DSP-7888 Dosing Emulsion 10.5 mg intradermal (ID), will start on Day 1, Q1W for first 4 
weeks, then Q2W thereafter 
• 
Nivolumab 240 mg IV, will start on Day 1 of Cycle 3 (Day 29), Q2W 
Arm 2 (Enrichment Cohort Only): DSP-7888 + pembrolizumab combination: 
• 
DSP-7888 Dosing Emulsion 10.5 mg ID, will start on Day 1, Q1W for first 3 weeks, then 
Q3W thereafter 
• 
Pembrolizumab 200 mg IV, will start on Day 1 of Cycle 2 (Day 22), Q3W 
Administration of DSP-7888 Dosing Emulsion and anti-PD-1 in the Phase 1b enrichment cohort is also 
depicted in Figure 3. 
Phase 2 
Approximately 40 eligible PROC patients are expected to be enrolled in the Phase 2 dose expansion 
part of the study.  
Objective disease assessments will be performed according to RECIST and iRECIST. For Phase 2, 
patients will be evaluated for objective response to study drug treatment with radiographic imaging 
every 6 weeks for 24 weeks and then every 12 weeks until progression. 
For patients enrolled under Protocol Amendment 4, the administration of DSP-7888 Dosing Emulsion 
and anti-PD1 in the Phase 2 dose expansion cohort is the same as that in the Phase 1b Arm 2 of the 
dose search part.  
For patients enrolled under Protocol Amendment 5, administration of DSP-7888 Dosing 
Emulsion and anti-PD1 will be staggered as follows: 
• 
DSP-7888 Doing Emulsion+ pembrolizumab combination: 
− DSP-7888 Dosing Emulsion 10.5 mg ID, will start on Day 1, Q1W for the first 3 
weeks, then Q3W thereafter 
− Pembrolizumab 200 mg IV, will start on Day 1 of Cycle 2 (Day 22), Q3W 
Phase 1b and Phase 2 
The safety and tolerability of DSP-7888 Dosing Emulsion in combination with immunotherapy PD-1 
inhibitors will be assessed for the duration of study treatment and follow-up. 
All adverse events (AEs) will be collected and recorded for each patient from the date of signing the 
main ICF for the study until 30 days after last study drug administration. Any serious adverse events 
(SAEs) related to study-related procedures will be collected starting from completion of the 
Prescreening informed consent form (ICF) (biomarkers sampling, blood drawings, and biopsy 
procedures). 
Number of patients (planned):  
In Phase 1b of the study, there will be approximately 6 to 12 patients for each arm, up to a total of 
24 patients. As part of these 24 patients, an enrichment cohort of 10 patients will be enrolled into Phase 
1b. If anti-tumor activities are observed in any tumor type, additional patients may be enrolled for 
further assessment. In Phase 2 of the study, approximately 40 patients will be enrolled. Additional 


 
 
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patients may be enrolled to further assess anti-tumor activities in the subgroups of interest. However, 
the total sample size of Phase 2 cannot exceed 60 patients. In total, approximately 64-84 patients will 
be enrolled in the study. 
Inclusion Criteria:  
Patients must fulfill each of the following requirements: 
Phase 1b 
Phase 1b Dose Search Part 
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: 
a) Patients must not be considered eligible for a potentially curative resection 
b) 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  


 
 
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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 (see Appendix 3) 
Both Phase 1b Dose Search Part and Phase 1b Enrichment Cohort: 
2. Patients must be positive for at least 1 of the following human leukocyte antigens (HLAs): 
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. ≥ 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 drug  
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 of study drug 
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 ULN or <5 × ULN if considered to be due to liver 
metastases 
11. Estimated glomerular filtration rate (GFR) >40 mL/min using the Cockcroft-Gault equation 
12. Multigated acquisition (MUGA) scan or echocardiogram (ECHO) with left ventricular ejection 
fraction (LVEF) >40% 
13. Life expectancy ≥3 months 
14. Patients must be willing to provide a signed and dated ICF 
Phase 2 
Patients eligible for inclusion in this study 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 standard of care 
2. Patients must be positive for at least 1 of the following HLAs as assessed by central 
laboratory: 
a) 
HLA-A*02:01 


 
 
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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 the 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  
a. 
Maintenance is not considered a separate line of treatment (even if patients who are 
BRCA mutation-positive received a PARP inhibitor following induction therapy with a 
platinum doublet, eg, bevacizumab)  
b. 
Neoadjuvant and adjuvant systemic therapy will be counted as one line of therapy 
c. 
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 (v.1.1) 
7. Patients must have an ECOG performance status of 0 or 1 
8. Patients must have adequate organ function, defined as follows: 
System 
Laboratory Value 
Hematologic  
Absolute neutrophil count (ANC) 
≥1,500 / μL (without granulocyte colony 
stimulating factor (G-CSF)) 
Platelets 
≥100,000 / μL (without transfusion) 
Hemoglobin 
≥9.0 g/dL (without transfusion) 
Renal 
Serum creatinine OR estimated GFR 
using the Cockcroft-Gault equation 
≤1.5 × ULN OR ≥40 mL/min using the 
Cockcroft-Gault equation for patients with 
creatinine levels >1.5 × ULN 
Hepatic 
Serum total bilirubin 
≤1.5 × ULN 
AST and ALT 
≤2.5 × ULN OR ≤5 × ULN for patients with 
liver metastases 
Cardiac 
MUGA or ECHO with LVEF 
≥40% 
QTcF (QT corrected based on 
Fridericia’s equation) interval  
<480 msec 


 
 
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Coagulation 
International Normalized Ratio 
(INR) or Prothrombin Time (PT) 
≤1.5 × ULN, unless the patient is receiving 
anticoagulant therapy and the PT is within 
therapeutic range  
Activated Partial Thromboplastin 
Time (aPTT) or Partial 
Thromboplastin Time (PTT) 
≤1.5 × ULN, unless the patient is receiving 
anticoagulant therapy and the aPTT is within 
therapeutic range 
9. Patients must provide either 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 to 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 for >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 (for females and males alike) after the last dose of study drug 
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:  
Patients with any of the following will be excluded from the study: 
Phase 1b  
Phase 1b Dose Search Part and Phase 1b Enrichment Part: 
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) within 
Phase 1b dose search part.  
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 (equivalent to >10 mg/day 
prednisone; see Appendix 2) 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 
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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, noninfectious pneumonitis 
9. Known hypersensitivity to a component of protocol therapy: 
a. Patients with known hypersensitivity to any of the components of DSP-7888 Dosing 
Emulsion 
b. 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 
nonmelanoma 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 QT corrected interval, based on Fridericia’s equation (QTcF), >480 msec 
(Common Terminology Criteria for Adverse Events [CTCAE] = Grade 2) or other factors that 
increase the risk of QT prolongation or arrhythmic events (eg, 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 active 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 (HBsAg) 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 
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 


 
 
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brain metastases and not have required systemic corticosteroids (equivalent to >10 mg/day 
prednisone; see Appendix 5) 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 immunoregulatory receptors or mechanisms 
(examples of such drugs include, but are not limited to, antibodies against, eg, 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 timeframe prior 
to the first dose of the study drug 
a. 
Cytotoxic chemotherapy, hormonal therapy; ≤3 weeks 
b. 
Targeted therapy except for monoclonal antibody; ≤3 weeks 
c. 
Immune therapy, biologic therapy (eg, antibodies); ≤4 weeks 
d. 
Other investigational agents: ≤4 weeks 
e. 
Radiation therapy (except for localized radiotherapy for analgesic purpose) ≤4 weeks 
f. 
Radiation therapy (localized radiotherapy for analgesic purpose) ≤1 week 
g. 
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:  
a. 
curatively treated basal cell or squamous cell carcinoma of skin 
b. 
curatively treated superficial bladder cancer, carcinoma in situ of the cervix,  
c. 
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 
exceptions 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 (equivalent to >10 mg/day 
prednisone; see Appendix 5) 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 active hepatitis C: 
• 
In cases of negative results for HBsAg with positive Hepatitis B 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 (NYHA) Class III or IV cardiac disease, including 
preexisting clinically significant ventricular arrhythmia, congestive heart failure, or 
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• 
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  
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. Patient who are pregnant or breastfeeding 
18. Patients who have a 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 
Duration of treatment:  
Patients will have access to study treatment as long as they are benefiting from study treatment in 
Phase 1b. 
For Phase 2 of the study, patients will have access to study treatment as long as they are benefiting 
from study treatment or have received up to a total of 35 treatment cycles (approximately 105 weeks). 
Patients may continue the study treatment beyond 35 treatment cycles if patients are experiencing 
clinical benefit after documented discussion with the Sponsor. 
Criteria for Evaluation 
Phase 1b 
Primary Endpoints 
• 
Incidence of DLTs, except for those patients treated in the enrichment cohort  
• 
Incidence and severity of AEs, SAEs  
• 
Dose interruption, reduction, and dose intensity 
Secondary Endpoints 
The following secondary efficacy endpoints will be evaluated per investigator assessment: 
• 
ORR, defined as proportion of patients who have achieved confirmed complete response (CR) 
or partial response (PR), evaluated using RECIST (v.1.1) and iRECIST based on investigator 
assessment 
• 
DCR, defined as the percentage of patients who have achieved best overall response (BOR) of 
CR, PR, or SD per RECIST (v.1.1) and iRECIST 


 
 
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• 
DOR, defined as the time from first documentation of a response (CR or PR) until time of first 
documentation of disease progression by RECIST (v.1.1) and iRECIST, or death by any cause 
• 
PFS, defined as the time from the date of the first dose of study treatment to the earlier date of 
assessment of progression by RECIST (v.1.1) and iRECIST, or death by any cause  
• 
6-month PFS Rate, defined as the proportion of patients who neither progressed by RECIST 
(v.1.1) and iRECIST nor died before 6 months (24 weeks) from the first study treatment 
• 
OS, defined as the time from the date of the first dose of study treatment to the date of death by 
any cause 
• 
Safety assessments: 
− AEs assessed according to CTCAE v4.03 
− DLT observed during the first 2 cycles  
− Dose interruption, reduction, and dose intensity per dose administration record 
− The incidence of treatment-emergent AEs (TEAEs) during the first 2 cycles compared 
with the third and subsequent cycles 
− The incidence of TEAEs occurring while patients are on treatment or up to 30 days 
after the last dose of study drug 
− The incidence of AEs that occur from signing the ICF until the first dose of treatment 
− The incidence of SAEs occurring while patients are on treatment through 30 days after 
the last dose of study drug 
− Changes in clinical laboratory parameters (hematology, chemistry, urinalysis), vital 
signs, ECOG performance status, electrocardiogram (ECG) parameters, physical 
examinations, and usage of concomitant medications (additional details in the schedule 
of assessments) 
Exploratory Endpoints 
Exploratory Biomarkers: 
Biomarkers using peripheral blood samples and tumor tissue samples in patients receiving DSP-7888 
Dosing Emulsion in combination with pembrolizumab may be evaluated for correlation with the 
following immunological changes and/or clinical responses: 
• 
WT1-specific cytotoxic T-lymphocytes (CTL) induction activity in blood samples 
• 
WT1 expression level via chromogenic in situ hybridization (CISH) and PD-L1 expression 
level via immunohistochemistry (IHC) 
• 
CD8+ cell density in tumor tissues  
• 
Tumor-infiltrating lymphocytes (TILs) profiling in tumor tissues 
• 
Immune profiling in tumor tissues with tumor inflammation signature analysis   
• 
Mutation status and tumor mutation burden (TMB) in tumor tissues 


 
 
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Other Exploratory Endpoints: 
• 
Progression-free survival ratio (PFSr) is defined as PFS1/PFS (-1) ratio using RECIST (v.1.1)  
− PFS1 is defined as the time from the date of first dose of study treatment to the earlier 
date of assessment of progression by RECIST (v.1.1), or death by any cause 
− PFS (-1) is defined as the date of initiation of the previous (penultimate) treatment 
regimen to the date of assessment of progression by RECIST (v.1.1) 
Phase 2 
Primary Endpoint 
The primary endpoint for the efficacy evaluation is ORR, defined as proportion of patients who have 
achieved confirmed CR or PR, evaluated using RECIST (v.1.1) based on investigator assessment. 
Secondary Endpoints 
The following secondary efficacy endpoints will be evaluated per investigator assessment:  
• 
DOR, defined as the time from the first documentation of a response (CR or PR) until time of 
first documentation of disease progression by RECIST (v.1.1), or death by any cause 
• 
DCR, defined as the percentage of patients who have achieved BOR of CR, PR, or SD per 
RECIST (v.1.1)   
• 
PFS, defined as the time from the date of the first dose of study treatment to the earlier date of 
assessment of progression by RECIST (v.1.1), or death by any cause  
• 
6-month PFS rate, defined as the proportion of patients who neither progressed by RECIST 
(v.1.1) nor died before 6 months (24 weeks) from the first study treatment 
• 
OS, defined as the time from the date of first dose of study treatment to the date of death by 
any cause 
• 
Immune objective response rate (iORR), defined as proportion of patients who have achieved 
confirmed immune complete response (iCR) or immune partial response (iPR), evaluated 
using iRECIST based on investigator assessment  
• 
Immune DCR (iDCR), defined as the percentage of patients who have achieved BOR of iCR, 
iPR, or immune stable disease (iSD), per iRECIST 
• 
Immune PFS (iPFS), 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 
• 
Immune DOR (iDOR), defined as the time from the first documentation of response (iCR or 
iPR) until time of first documentation of disease progression by iRECIST, or death by any 
cause  
• 
Safety Assessments: frequency and intensity of AEs assessed according to CTCAE v4.03. 
Exploratory Endpoints 
Exploratory Biomarkers: 
Biomarkers using peripheral blood samples and tumor tissue samples in patients receiving DSP-7888 
Dosing Emulsion in combination with pembrolizumab biomarkers may be evaluated for correlation 
with the following immunological changes and/or clinical responses 


 
 
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• 
WT1-specific CTL induction activity in blood samples  
• 
WT1 via CISH and PD-L1 expression status (CPS) via IHC in tumor tissue  
• 
CD8+ cell density in tumor tissues  
• 
TILs profiling in tumor tissues  
• 
Immune profiling in tumor tissues with tumor inflammation signature analysis   
• 
Mutation status and mutational burden analysis in tumor tissues 
Other Exploratory Endpoints: 
• 
Progression-free survival ratio (PFSr) is defined as PFS1/PFS (-1) ratio using RECIST (v.1.1)  
− PFS1 is defined as the time from the date of first dose of study treatment to the earlier 
date of assessment of progression by RECIST (v.1.1), or death by any cause 
− PFS (-1) is defined as the date of initiation of the previous (penultimate) treatment 
regimen to the date of assessment of progression by RECIST (v.1.1) 
• 
CA-125 response rate is defined as proportion of patients who have achieved response using 
the Gynecologic Cancer InterGroup (GCIG) CA-125 response definition 
• 
Time to progression with CA-125 is defined as the time from the date of first dose of study 
treatment to the earlier date of assessment of progression by GCIG CA-125 progression 
definition or death by any cause 
• 
HLA typing 
Statistical Methods: 
In general, all efficacy and safety endpoints will be analyzed using descriptive statistics (n, mean, 
standard deviation, median, and ranges for continuous variables; frequencies and percentages for 
categorical variables). Kaplan-Meier methods will be used to summarize time-to-event endpoints (OS, 
PFS, and DOR). Primary efficacy of ORR will be analyzed using the Bayesian approach defined in the 
statistical analysis plan (SAP). Other efficacy analyses will be performed on the full analysis set 
(FAS).  
Detailed methodology for the statistical analyses of the data collected in this study will be documented 
in the SAP, which will be maintained by 
 The SAP may modify the plans outlined in 
the protocol; however, any major modifications of the primary endpoint definition and/or its analysis 
will also be reflected in a protocol amendment. 
Patient responses will be assessed based on RECIST v1.1 and iRECIST. Data listings and summaries 
may include tumor markers, additional imaging, or other response data. Potential relationships between 
biomarker and other response data may be evaluated. For Phase 2, primary efficacy of ORR with 
RECIST v 1.1 will be analyzed using the Bayesian approach defined in the SAP, based on ES. Other 
efficacy analyses will be performed on the FAS. Progression-free survival ratio will be summarized for 
both the Phase 1b enrichment cohort and for Phase 2.   
For Phase 2 Cohort Only 
There is no formal hypothesis testing for the Phase 2 cohort. A Bayesian decision-making framework 
will be employed to quantify whether proof of concept (POC) can be established based on the overall 
response rate (ORR) by Week 24 from the final analysis for the overall population and/or the CPS 
< 10 subpopulation. The POC is established at the final analysis if either or both of the following 
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• 
In the overall population, 70% credible interval of ORR with 10% in the left tail and 20% 
in the right tail will be calculated: if lower bound ≥ 8% and upper bound ≥ 21% (where 8% 
is the reference value [Section 4.3.1] and 21% is the target value of ORR in the overall 
population), the study will achieve POC. 
• 
In the CPS< 10 subpopulation, 50% credible interval of ORR with 20% in the left tail and 
30% in the right tail will be calculated: if lower bound ≥ 5% and upper bound ≥ 15% 
(where 5% is the reference value [Section 4.3.1] and 15% is the target value of ORR in 
CPS < 10 subpopulation), the study will achieve POC.  
The interim monitoring analysis for futility early efficacy assessment will be conducted using a 
Bayesian method and will start after the first 20 patients have response evaluation, withdraw, or die by 
Week 24.  
• 
If the posterior probability of ORR ≥ 21% in the overall population is ≤ 2.5% AND the 
posterior probability of ORR ≥ 15% in the CPS < 10 subpopulation is ≤ 2.5%, the study is 
futile and further enrollment will be stopped. 
• 
If the posterior probability of ORR ≥ 21% in overall population is ≥ 80% AND the posterior 
probability of ORR ≥ 15% in CPS < 10 subpopulation is ≥ 70%, then early success is met and 
further enrollment may be stopped.   
• 
Otherwise, the enrollment will continue as is until 40 patients.  
The above decision rules for interim analysis are non-binding.  
A total of 20 to 40 patients will be enrolled for this cohort. Additional patients may be enrolled to 
further assess anti-tumor activities in the subgroups of interest. However, the total sample size of Phase 
2 part cannot exceed 60 patients. 
Adverse events will be assessed according to CTCAE v4.03, when appropriate, and will be evaluated 
by grade and System Organ Class (SOC). Adverse event listings and tabulated summaries of 
categorized AEs will be generated by dose level and patients overall, for each study arm, and study 
phase. Additionally, the number of patients enrolled, number evaluable for dose search, and number 
with DLTs will be described for each dose level, patients overall, and each study arm in Phase 1b, the 
dose search part of the study. Vital signs, laboratory data, and ECG data, stratified by dose level and 
overall for each study arm and phase, will be summarized for changes over time at each postbaseline 
visit, together with the change from baseline. 
Antitumor activity will be evaluated and will be summarized using descriptive statistics. Analyses will 
be performed both for all patients enrolled and for patients evaluable for response in the FAS. Data 
listings and summaries may include tumor markers, additional imaging, or other response data. 
Potential relationships between drug administration, PD, and other response data may be evaluated. 
Kaplan-Meier estimates of OS and PFS will be generated. 
 
 
 


 
 
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TABLE OF CONTENTS 
1. 
TITLE PAGE .................................................................................................................... 1 
SIGNATURE PAGE ............................................................................................................................ 2 
INVESTIGATOR’S AGREEMENT................................................................................................... 3 
CONTACT INFORMATION .............................................................................................................. 4 
2. 
SYNOPSIS ........................................................................................................................ 5 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................. 26 
4. 
INTRODUCTION .......................................................................................................... 30 
4.1. 
Disease Background ....................................................................................................... 30 
4.2. 
Investigational Product Background and Mechanism of Action ................................. 30 
4.3. 
Rationale for Study ......................................................................................................... 31 
4.3.1. 
Rationale for the Study Population ................................................................................ 31 
4.3.1.1. 
Rationale for Dose Selection.......................................................................................... 32 
4.3.2. 
Current Status of 
Sponsored Studies ................................................... 34 
4.3.3. 
Nonclinical Studies ......................................................................................................... 34 
4.3.3.1. 
Primary Pharmacology ................................................................................................... 34 
4.3.3.2. 
Pharmacokinetics ............................................................................................................ 35 
4.3.3.3. 
Toxicology ...................................................................................................................... 36 
4.3.4. 
Clinical Studies ............................................................................................................... 38 
5. 
STUDY OBJECTIVES AND ENDPOINTS ................................................................ 39 
6. 
INVESTIGATIONAL PLAN ........................................................................................ 44 
6.1. 
Overall Study Design ..................................................................................................... 44 
6.1.1. 
Phase 1b ........................................................................................................................... 45 
6.1.2. 
Dose Search Part ............................................................................................................. 45 
6.1.3. 
Enrichment Part .............................................................................................................. 45 
6.1.4. 
Phase 2 ............................................................................................................................. 46 
6.1.4.1. 
Duration of Treatment .................................................................................................... 46 
6.1.4.2. 
Prescreening Period ........................................................................................................ 47 
6.1.4.3. 
Screening Period ............................................................................................................. 47 
6.1.4.4. 
Treatment Period............................................................................................................. 47 
6.1.4.5. 
Follow-up Period ............................................................................................................ 48 
6.2. 
Planned Number of Patients ........................................................................................... 50 


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6.3. 
Treatment Assignment ................................................................................................... 50 
6.3.1. 
Phase 1b ........................................................................................................................... 50 
6.3.2. 
Phase 2 (Dose-Expansion Part)...................................................................................... 52 
6.4. 
Dose-limiting Toxicities (Phase 1b Dose Search Part Only) ....................................... 53 
6.5. 
Defining Recommended Dose of DSP-7888 Dosing Emulsion with 
Nivolumab or Pembrolizumab (Only Phase 1b Dose Search Part) ............................. 54 
6.6. 
Safety Review Committee.............................................................................................. 55 
6.7. 
Procedures ....................................................................................................................... 55 
7. 
SELECTION AND WITHDRAWAL OF PATIENTS................................................ 68 
7.1. 
Inclusion Criteria ............................................................................................................ 68 
7.2. 
Exclusion Criteria ........................................................................................................... 71 
7.3. 
Withdrawal Criteria ........................................................................................................ 75 
7.3.1. 
Reasons for Discontinuation of Protocol Therapy........................................................ 75 
7.3.2. 
Reasons for Discontinuation from the Clinical Study .................................................. 75 
8. 
TREATMENT OF PATIENTS ..................................................................................... 77 
8.1. 
Description of Study Drugs............................................................................................ 77 
8.1.1. 
DSP-7888 Dosing Emulsion Investigational Product .................................................. 77 
8.1.2. 
Nivolumab ....................................................................................................................... 77 
8.1.3. 
Pembrolizumab ............................................................................................................... 77 
8.2. 
Treatment Dose and Schedule (Phase 1 and Phase 2) .................................................. 77 
8.3. 
Dose Modification .......................................................................................................... 79 
8.3.1. 
DSP-7888 Dosing Emulsion Dose Modification in Phase 1b ..................................... 79 
8.3.2. 
DSP-7888 Dosing Emulsion Dose Modification in Phase 2........................................ 79 
8.3.2.1. 
Dose Reduction ............................................................................................................... 79 
8.3.2.2. 
Dose Interruption ............................................................................................................ 79 
8.3.3. 
Pembrolizumab and Nivolumab Dosing Management in Phase 1b and Phase 
2 ....................................................................................................................................... 80 
8.3.4. 
Settings and Recommendations for DSP-7888 Dosing Emulsion Injections ............. 80 
8.3.5. 
Evaluation and Management of Injection Site Reactions ............................................ 80 
8.3.5.1. 
Evaluation of Injection Site Reactions .......................................................................... 80 
8.3.5.2. 
Management Guidelines for Grade 1 Injection Site Reactions .................................... 81 
8.3.5.3. 
Management Guidelines for Grade 2/3 Injection Site Reactions ................................ 81 
8.4. 
Packaging and Labeling ................................................................................................. 82 


 
 
  
 
 
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8.5. 
Prior and Concomitant Therapy ..................................................................................... 82 
8.6. 
Permitted Treatment ....................................................................................................... 82 
8.7. 
Prohibited Medication/Therapy ..................................................................................... 83 
8.8. 
Note on Nivolumab/Pembrolizumab and Systemic Immunosuppression ................... 83 
8.9. 
Treatment Compliance ................................................................................................... 84 
8.10. 
Randomization ................................................................................................................ 84 
8.11. 
Blinding ........................................................................................................................... 84 
9. 
STUDY DRUG MATERIALS AND MANAGEMENT ............................................. 85 
10. 
PHARMACODYNAMIC AND TUMOR TISSUE ASSESSMENTS ....................... 86 
10.1. 
Tumor Tissue Collection Procedure .............................................................................. 86 
10.1.1. 
Phase 1b and Phase 2 ...................................................................................................... 86 
10.1.2. 
Follow-Up Procedures .................................................................................................... 86 
10.2. 
Pharmacodynamic Variables (Biomarkers) .................................................................. 87 
11. 
ASSESSMENTS OF SAFETY AND EFFICACY ...................................................... 88 
11.1. 
Assessment of Safety ...................................................................................................... 88 
11.1.1. 
Safety Parameters ........................................................................................................... 88 
11.1.1.1. 
Vital Signs ....................................................................................................................... 88 
11.1.1.2. 
Physical Examination ..................................................................................................... 88 
11.1.1.3. 
Cardiac Assessments ...................................................................................................... 88 
11.1.1.4. 
Laboratory Assessments ................................................................................................. 88 
11.1.2. 
Adverse and Serious Adverse Events ............................................................................ 89 
11.1.2.1. 
Definitions ....................................................................................................................... 89 
11.1.2.2. 
Procedures for Eliciting, Recording, and Reporting Adverse Events ......................... 91 
11.1.2.3. 
Specific Instructions for Recording Adverse Events on the eCRF.............................. 93 
11.1.2.4. 
Reporting of Expedited Safety Observations by the Investigator Including 
Serious Adverse Events .................................................................................................. 95 
11.2. 
Assessment of Efficacy .................................................................................................. 97 
12. 
STATISTICS .................................................................................................................. 98 
12.1. 
Statistical Methods.......................................................................................................... 98 
12.1.1. 
Determination of Sample Size ....................................................................................... 98 
12.1.1.1. 
Dose-search Part (Phase 1b) .......................................................................................... 98 
12.1.1.2. 
Dose-Expansion Part (Phase 2)...................................................................................... 98 
12.1.2. 
Analysis Datasets ............................................................................................................ 99 


 
 
  
 
 
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12.1.2.1. 
Full Analysis Set ............................................................................................................. 99 
12.1.2.2. 
Safety Set......................................................................................................................... 99 
12.1.2.3. 
Dose-Determining Set .................................................................................................... 99 
12.1.2.4. 
Efficacy Set ..................................................................................................................... 99 
12.1.3. 
Handling of Missing Data .............................................................................................. 99 
12.1.4. 
Demographic and Baseline Characteristics ................................................................. 100 
12.1.5. 
Data Analyses ............................................................................................................... 100 
12.1.5.1. 
Efficacy Analysis .......................................................................................................... 100 
12.1.5.2. 
Safety Analysis ............................................................................................................. 100 
12.1.5.3. 
Pharmacodynamics, Biomarkers, and Exploratory Analysis ..................................... 100 
12.1.5.4. 
Interim Analysis ............................................................................................................ 101 
13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS ........................................ 102 
13.1. 
Study Monitoring .......................................................................................................... 102 
13.2. 
Audits and Inspections ................................................................................................. 102 
13.3. 
Institutional Review Board/Independent Ethics Committee ...................................... 102 
14. 
QUALITY CONTROL AND QUALITY ASSURANCE ......................................... 103 
15. 
ETHICS ......................................................................................................................... 104 
15.1. 
Ethics Review ............................................................................................................... 104 
15.2. 
Ethical Conduct of the Study ....................................................................................... 104 
15.3. 
Informed Consent ......................................................................................................... 104 
16. 
DATA HANDLING AND RECORDKEEPING ....................................................... 106 
16.1. 
Data Protection.............................................................................................................. 106 
16.2. 
Source Documents ........................................................................................................ 106 
16.3. 
Inspection of Records ................................................................................................... 106 
16.4. 
Retention of Records .................................................................................................... 107 
17. 
PUBLICATION POLICY ............................................................................................ 108 
18. 
LIST OF REFERENCES ............................................................................................. 109 
19. 
APPENDICES .............................................................................................................. 111 
APPENDIX 1. EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE 
STATUS SCORES ....................................................................................................... 112 
APPENDIX 2. RESPONSE EVALUATION CRITERIA IN SOLID TUMORS..................... 113 
APPENDIX 3. IMMUNE-RESPONSE EVALUATION CRITERIA IN SOLID 
TUMORS (IRECIST) ................................................................................................... 116 


 
 
  
 
 
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APPENDIX 4. CA-125 GYNECOLOGIC CANCER INTER GROUP CRITERIA* .............. 120 
APPENDIX 5. GLUCOCORTICOID DOSE EQUIVALENTS ................................................ 122 
APPENDIX 6. COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS ......... 123 
APPENDIX 7. PHASE 2 STUDY DESIGN FLOW................................................................... 124 
APPENDIX 8. LEGACY PHASE 1 TREATMENT SCHEDULE............................................ 125 
 


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LIST OF TABLES 
Table 1: 
Contact Information .......................................................................................................... 4 
Table 2: 
Abbreviations and Special Terms .................................................................................. 26 
Table 3: 
Study Objectives, Endpoints, and Assessments............................................................ 39 
Table 4: 
Phase 1b Study Dose Level and Schedule .................................................................... 52 
Table 5: 
PD-1 Inhibitor Dose........................................................................................................ 52 
Table 6: 
Phase 2 Study Dosing Schedule..................................................................................... 52 
Table 7: 
Schedule of Assessments (Arm 1, Combination of DSP-7888 Dosing 
Emulsion and Nivolumab [14-Day Study Cycles]) ...................................................... 57 
Table 8: 
Schedule of Assessment (Arm 2 of Phase 1b, Combination of DSP-7888 
Dosing Emulsion and Pembrolizumab [21-Day Study Cycles]) ................................. 60 
Table 9: 
Schedule of Assessments (Phase 2, Combination of DSP-7888 Dosing 
Emulsion and Pembrolizumab for Ovarian Cancer)..................................................... 63 
Table 10: DSP-7888 Dosing Emulsion, Nivolumab, and Pembrolizumab Treatment 
Dose and Schedule .......................................................................................................... 78 
Table 11: Grading of Injection Site Reactions (CTCAE v4.03) ................................................... 81 
Table 12: Legacy Phase 1* DSP-7888 Dosing Emulsion, Nivolumab, and 
Pembrolizumab Treatment Dose and Schedule .......................................................... 125 
 
 


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LIST OF FIGURES 
Figure 1: 
Effect of the Number of Doses of Cancer Vaccine on the Induction of 
WT1126-134 -reactive T Cells ........................................................................................... 34 
Figure 2: 
Overall Study Design ..................................................................................................... 44 
Figure 3: 
Schematic of Study Arm 1 and Study Arm 2 in Phase 1b ........................................... 50 
Figure 4: 
Schematic of Phase 2 of Study....................................................................................... 50 
Figure 5: 
Schematic of Legacy Study Conduct .......................................................................... 126 
 


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Table 2: 
Abbreviations and Special Terms  
AE 
adverse event 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time  
AST 
aspartate aminotransferase 
BBI 
Boston Biomedical, Inc (former name of 
  
BOR 
best overall response 
cGCP 
current Good Clinical Practice 
CISH 
chromogenic in situ hybridization  
CPS 
combined positive score 
CR 
complete response 
CRF 
case report form 
CRP 
C-reactive protein 
CSR 
clinical study report 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTL 
cytotoxic T lymphocyte 
DCR 
disease control rate 
DDS 
dose-determining set 
DLT 
dose-limiting toxicity 
DOR 
duration of response 
DSP-7888 Dosing Emulsion 
Ombipepimut-S (Nelatimotide and Adegramotide) / 
Ombipepimut-S Suspension with Montanide  
DSP-7888 
(Adegramotide/Nelatimotide 
[INN] and Ombipepimut-S 
[USAN]) 
code name for the dipeptide vaccine of DSP-7888-H and 
DSP-7888-K  
DSP-7888-H 
DSP-7888-H (adegramotide [INN]) helper peptide 
DSP-7888-K 
DSP-7888-K (nelatimotide [INN]) cytotoxic T 
lymphocyte-inducing (killer) peptide 


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ECG 
electrocardiogram 
ECHO 
echocardiogram 
ECOG 
Eastern Cooperative Oncology Group (performance status) 
eCRF 
electronic case report form 
ES 
efficacy set 
FAS 
full analysis set 
FFPE 
formalin-fixed and paraffin-embedded 
GCIG 
Gynecologic Cancer InterGroup 
G-CSF 
granulocyte-colony stimulating factor  
GFR 
glomerular filtration rate 
GLP 
Good Laboratory Practices 
HBsAg 
HBV 
hepatitis B surface antigen 
hepatitis B virus 
HCC 
hepatocellular carcinoma 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
HNSCC 
head and neck squamous cell carcinoma(s) 
HNSTD 
highest non-severely toxic dose 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonisation  
iCPD 
immune confirmed progressive disease per iRECIST 
iCR 
immune complete response 
iDCR 
immune disease control rate 
iDOR 
immune duration of response 
IEC 
independent ethics committee 
IHC 
immunohistochemistry 
INR 
international normalized ratio 
IRB 
institutional review board 
iRECIST 
immune Response Evaluation Criteria in Solid Tumors 
iORR 
immune objective response rate 
iPFS 
immune progression-free survival 


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iPR 
immune partial response 
irAE 
Immune related adverse event 
iSD 
immune stable disease 
ISR 
injection site reaction 
iUPD 
immune unconfirmed progressive disease per iRECIST 
IV 
intravenous(ly) 
LoQ 
limit of quantification 
LVEF 
left ventricular ejection fraction 
MRI 
magnetic resonance imaging 
MSI-H/dMMR 
microsatellite instability-high or mismatch repair-deficient  
MUGA 
multigated acquisition 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NOAEL 
no-observed adverse effect level 
NSCLC 
non-small cell lung cancer 
NYHA 
New York Heart Association 
ORR 
objective response rate 
OS 
overall survival 
PBMCs 
peripheral blood mononuclear cells 
PD 
pharmacodynamic(s) 
PD-L1 
programmed death ligand 1 
PD-L2 
programmed death ligand 2 
PD-1 
programmed cell death protein 1 
PFS 
progression-free survival 
PFSr 
progression-free survival rate 
PK 
pharmacokinetic(s) 
PR 
partial response 
PROC 
platinum-resistant ovarian cancer 
PT 
prothrombin time  
PTT 
partial thromboplastin time 
Q1W 
once every week 


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Q3W 
once every 3 weeks 
QTcF 
corrected QT using the Fridericia equation 
RCC 
renal cell carcinoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SD 
stable disease 
 
 Inc., the Sponsor 
SOA 
schedule of assessments 
SOC 
System Organ Class 
SpO2 
blood saturation oxygen level 
SRC 
Safety Review Committee 
SS 
Safety set 
TB 
bacillus tuberculosis 
TEAE 
treatment-emergent adverse event 
TIL 
tumor-infiltrating lymphocytes 
TMB 
tumor mutation burden 
ULN 
upper limit of normal 
US 
United States 
WHO 
World Health Organization 
WT1 
Wilms Tumor 1 
 
 


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4. 
INTRODUCTION 
4.1. 
Disease Background  
It is estimated that in 2017, there will be 1,688,780 new cases of cancers in the United States 
(US) alone, with an estimated 600,920 cancer deaths; there were 8.8 million cancer deaths 
worldwide in 2015 (American Cancer Society, 2017; World Health Organization [WHO]). 
Consequently, there is a significant unmet medical need for the development of novel treatments 
for advanced solid tumors. 
Ovarian cancer comprises multiple histologic subtypes, with epithelial ovarian cancer 
constituting approximately 90% of malignant ovarian cancers (National Comprehensive Cancer 
Network [NCCN] Guidelines 2019). Ovarian cancer is the seventh most common neoplasm for 
women worldwide, with more than 238,000 cases and >150,000 deaths in 2012 (Torre, 2018). In 
2018, it was estimated that 22,240 new diagnoses and 14,070 deaths from ovarian cancer would 
occur in the US; less than 40% of women with ovarian cancer are cured (Siegel, 2018). More 
than 70% of patients with ovarian cancer present with stage III or IV disease, and a high 
percentage of patients with high-grade serous histology present with advanced disease  
(Kobel, 2010; Seidman, 2004). Approximately 90% of ovarian cancer patients with serous 
histology are positive, with Wilms Tumor 1 (WT1) in their tumors (McCluggage, 2015). Primary 
cytoreductive (debulking) surgery followed by platinum-based chemotherapy, with or without 
concurrent and maintenance bevacizumab, represents the currently recommended standard 
first-line systemic treatment, although most patients develop recurrence, with a median 
progression-free survival (PFS) time of 12 to 18 months (Jiang, 2014). Furthermore, patients 
who relapse within 6 months of completing first-line therapy have been classified as being 
“platinum resistant,” and typically have low response rates to subsequent chemotherapy (15%), 
with a PFS of 3 to 4 months and a median survival under a year (Davis, 2014). Thus, more 
efficient treatment methods are warranted to improve the survival of ovarian cancer patients. 
4.2. 
Investigational Product Background and Mechanism of Action 
Nelatimotide and Adegramotide Dosing Emulsion (Ombipepimut-S Suspension with Montanide; 
hereafter referred to as DSP-7888 Dosing Emulsion) is a synthetic peptide vaccine that consists 
of 2 synthetic peptide constructs: nelatimotide (INN) (DSP-7888-K [killer peptide; an MHC 
Class I peptide]) and adegramotide (INN) (DSP-7888-H [helper peptide; an MHC Class II 
peptide]). Both constructs are derived from the WT1 protein. DSP-7888 Dosing Emulsion, a 
DSP-7888 solution mixed with montanide ISA 51 VG (labeled as DSP-7888-M). This will be 
administered at the study site by staff trained in the administration of intradermal drugs. 
Specifically, DSP-7888-K is a conjugate consisting of the WT1126-134 peptide sequence and the 
modified WT1235-243 peptide sequence, whereas DSP-7888-H corresponds to the WT134-51 
sequence. The emulsion acts as a depot and enhances the immunogenicity of the DSP-7888-K 
and DSP-7888-H peptides.  
DSP-7888 Dosing Emulsion is applicable for the patient who has at least 1 of 5 human leukocyte 
antigen (HLA) types: HLA-A*02:01, HLA-A*02:06, HLA-A*24:02, HLA-A*03:01, and HLA-
B*15:01, which are expected to cover approximately 76.4% of North American Natives, 68.9% 
of Caucasians, 65.3% of Hispanics, 56.8% of Asians, and 42.2% of African Americans in the US 
population (Cao, 2001). 


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DSP-7888 Dosing Emulsion is administered intradermally or subcutaneously and is expected to 
be presented on the surface of antigen-presenting cells as an MHC Class I peptide complex that 
can be recognized by CD8+ cytotoxic T lymphocytes (CTLs.) As a consequence, vaccination 
with DSP7888 Dosing Emulsion may stimulate the host immune system to induce a CTL 
response against cancer cells overexpressing the WT1 protein, resulting in cell lysis and 
inhibition of cancer cell proliferation. Addition of the MHC Class II peptide is expected to show 
efficacy over that observed with a treatment regimen of the MHC Class I peptide alone. 
Intradermal administration is selected in this study based on the data showing higher 
WT1-specific CTL induction activity in patients who received intradermal administration of 
DSP-7888 Dosing Emulsion than those who had received subcutaneous administration of 
DSP-7888 Dosing Emulsion. Further details can be found in the Investigator’s Brochure. 
4.3. 
Rationale for Study 
4.3.1. 
Rationale for the Study Population 
The combination of cancer vaccines like DSP-7888 Dosing Emulsion with checkpoint inhibitors 
(programmed cell death-1 [PD-1]/programmed death ligand 1 [PD-L1]) represents a feasible 
option to improve clinical benefit and a way to reverse resistance to immunomodulators  
(Morse, 2015). The vaccine significantly enhances infiltration by CD8+ T cells that allows the 
priming and intratumoral recruitment of these cells, and could possibly transform a “non-
inflamed,” non-permissive tumor that is resistant to checkpoint inhibitors into a sensitive, 
“inflamed” tumor that is responsive to checkpoint inhibitor blockade. Interferon gamma 
production by antitumor-specific T cells could also upregulate PD-L1 on tumor cells as a 
resistance mechanism to adaptive immunity, thereby promoting PD-L1/PD-1 after vaccination 
(Morse, 2015). 
The proposed panel of tumor types selected for the Phase 1b part of the study was based on 
higher expression of WT1 in these tumors, as well as promising clinical activities of checkpoint 
inhibitors in those tumor types (Goto, 2016). However, for the Phase 2 part of this study, ovarian 
cancer has been selected, as approximately 90% of the patients are WT1-positive in their tumors 
(Goldstein, 2002; Hwang, 2004). 
The data of KEYNOTE-100 (an open-label Phase 2 study of pembrolizumab monotherapy for 
patients with recurrent ovarian cancer) demonstrated that pembrolizumab monotherapy in 
recurrent ovarian cancer elicited modest antitumor efficacy (objective response rate 
[ORR]:8.0%). Moreover, patients with Combined Positive Score ([CPS] ie, PD-L1 expression in 
tumor cells and immune cells) ≥10 had an ORR of 17.1% compared to an ORR of approximately 
5% in patients with CPS <10. Although several studies, including KEYNOTE-100, demonstrate 
an activity of checkpoint inhibitors in recurrent ovarian cancer (Matulonis, 2019), and the 
patients who respond to checkpoint inhibitors have a long-term benefit from the treatment, they 
are not comparable to the results in other solid tumors (eg melanoma). The combination of 
cancer vaccines, like DSP-7888 Dosing Emulsion with checkpoint inhibitor, could possibly 
transform a “non-inflamed” tumor such as ovarian cancer into “inflamed” tumor to enhance 
infiltration by CD8+ T cells. In a preclinical model of leukemia, it has been demonstrated that 
cancer vaccines cooperated with checkpoint blockade and allowed for immune control of cancers 
with low nonsynonymous mutation loads (Manlove, 2016). In a preclinical study of DSP-7888 
Dosing Emulsion, the activity of DSP-7888-induced CTLs was further enhanced by treatment 


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with anti-PD-1 antibody. Additionally, antitumor activities of DSP-7888 and anti-PD-1 antibody 
were enhanced by their combination in the HLA-transgenic mouse model compared with 
DSP-7888 Dosing Emulsion alone or anti-PD-1 antibody alone (Goto, 2016). 
4.3.1.1. 
Rationale for Dose Selection 
A GLP repeat-dose toxicity study with DSP-7888 Dosing Emulsion demonstrated that neither a 
low dose (3.5 mg, consisting of 2.0 mg killer peptide + 1.5 mg helper peptide) nor a high dose 
(17.5 mg, consisting of 10.0 mg killer peptide + 7.5 mg helper peptide) resulted in 
treatment-related effects on body weight, food consumption, ophthalmologic examination, 
electrocardiography, body temperature, blood pressure, respiratory rate, immunophenotyping in 
peripheral blood, or organ weights in the cynomolgus monkeys. The main toxicities observed 
were ISRs (erythema, induration, and crust), which were more pronounced in the high-dose 
group. Under the conditions of this study, the NOAEL of DSP-7888 Dosing Emulsion was not 
determined. The HNSTD was declared as the high dose of DSP-7888 Dosing Emulsion 
(DSP-7888-K 10 mg/body + DSP-7888-H 7.5 mg/body).  
In the Phase 1b dose search part, the higher starting dose of 10.5 mg (Level 1) of DSP-7888 
Dosing Emulsion was selected based on studies that showed higher WT1-specific CTL induction 
with this dose. Patients with 10.5 mg administration showed stronger and earlier CTL induction 
than patients with 3.5 mg administration with similar safety profiles (Miyakoshi, 2016).  
The recommended dose from Phase 1b dose search part will be used in the Phase 1b enrichment 
part and the Phase 2 part. In the absence of any dose-limiting toxicities (DLTs) identified in 
Phase 1b of the study, 10.5 mg of DSP-7888 Dosing Emulsion will be the recommended Phase 2 
dose.  
For those patients enrolled under Protocol Amendment 5, the administration schedule of 
DSP-7888 dosing emulsion and anti-PD-1 antibody will differ from that in the completed Phase 
1b dose search part, and will be staggered as follows: 
1. Timing of integration of anti-PD-1 antibody into DSP-7888 Dosing Emulsion: 
• DSP-7888 Dosing Emulsion + nivolumab combination: 
− DSP-7888 Dosing Emulsion 10.5 mg ID, beginning on Day 1, Q1W for first 
4 weeks, then Q2W thereafter 
− Nivolumab 240 mg IV, beginning on Day 1 of Cycle 3 (Day 29), Q2W 
• DSP-7888 Dosing Emulsion + pembrolizumab combination: 
− DSP-7888 Dosing Emulsion 10.5 mg ID, beginning on Day 1, Q1W for first 
3 weeks, then Q3W thereafter 
− Pembrolizumab 200 mg IV, beginning on Day 1 of Cycle 2 (Day 22), Q3W 
Cancer vaccines, including neoantigens, are currently being explored in combination with 
anti-PD-1 and anti-PD-L1 antibodies in several clinical trials with the intent to reinvigorate T 
cell-mediated tumor killing and enhance the anti-PD-1 effect. However, since the PD-1 pathway 
plays an important role in the balance of T cell activation and tolerance (Patsoukis N, 2017), 
identifying the optimal timing or sequencing of PD-1 blockade with respect to T cell receptor 
(TCR) engagement and the status of T cell priming is essential to achieve maximum therapeutic 


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benefits. In mouse tumor models that are known to be resistant to anti-PD-1 therapy, PD-1 
blockade in suboptimally primed CD8+ T cell conditions results in the generation of 
dysfunctional PD-1+CD38hi CD8+ cells, leading to resistance to anti-PD-1 antibody and 
therapeutic failure. On the other hand, optimal antigenic stimulation reverses anti-PD-1 
resistance. These results suggest that (1) concomitant treatment with anti-PD-1 in suboptimal 
priming conditions confers resistance to immunotherapy that can be reversed by proper antigen 
stimulation and (2) appropriate sequencing of immunomodulatory agents is crucial for 
therapeutic outcomes (Verma, 2019). In addition, Pauken et al. show that constitutive loss of PD-
1 during acute infection causes overactivation of CD8+ T cells during the effector phase and 
impairs memory and recall responses. These data indicate PD-1 is required for optimal memory 
(Pauken, 2020). Based on the recent finding above, anti-PD-1 antibody therapy will be integrated 
in a staggered schedule into DSP-7888 Dosing Emulsion from Day 29 (Arm 1) or Day 22 (Arm 
2), based on the choice of combination therapy, when optimal priming of WT1-specific CTL by 
DSP-7888 Dosing Emulsion has been expected.  
2. Duration of induction phase for combination with pembrolizumab: 
Per Protocol Amendment 5, the long duration of the 6-week induction phase is shortened to 
3 weeks. 
A nonclinical in vivo pharmacology study was conducted to evaluate the trend of induction of 
HLA-A*02:01-restricted T cells that recognize the WT1126-134 peptide using HLA-A*02:01 
transgenic mice. A weekly DSP-7888-like cancer vaccine, which was prepared by mixing 
MONTANIDE ISA 51 VG and aqueous antigenic peptide solution containing Nelatimotide 
Trifluoroacetate and Adegramotide Acetate but without any additives, was administered once, 
twice, three, or four times. 7 days after the final administration, splenocytes were prepared from 
each mouse and evaluated to measure the number of HLA-A*02:01-restricted T cells that 
recognize the WT1126-134 peptide with IFN-γ ELISPOT assay. As a result, there was a statistically 
downward trend in the induction with an increasing number of administrations of the weekly 
cancer vaccine. (p=0.0466; Figure 1).  


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Figure 1: 
Effect of the Number of Doses of Cancer Vaccine on the Induction of 
WT1126-134 -reactive T Cells 
Legend: The number of WT1126-134-reactive T cells induced by the DSP-7888-like cancer vaccine in HLA-
A*02:01 transgenic mice. HLA-A*02:01 Tg mice were intradermally administered DSP-7888-like cancer 
vaccine containing 0.1 mg of Nelatimotide Trifluoroacetate and 0.1 mg of Adegramotide Acetate once, twice, 
three, or four times (n = 3 animals/group). 7 days after the final administration, splenocytes were prepared 
from each mouse and evaluated to measure the number of HLA-A*02:01-restricted T cells that recognize the 
WT1126-134 peptide with IFN-γ ELISPOT assay. Values are the mean ± standard deviation of each group of 
IFN-γ ELISPOT assay. p=0.0466 (Jonckheere-Terpstra). 
4.3.2. 
Current Status of 
Sponsored Studies 
DSP-7888 Dosing Emulsion is currently under clinical investigation in 2 studies including the 
DSP-7888 102CI study and a multi-national Phase 3 study in patients with recurrent or 
progressive glioblastoma. These 2 studies are ongoing, and additional information regarding 
DSP-7888 Dosing Emulsion can be found in the current Investigator’s Brochure.  
DSP-7888 Dosing Emulsion has been well tolerated thus far. Overall, the most frequently 
observed adverse event (AE) is injection site reaction (ISR).  
Thirteen patients already have been enrolled into the Phase 1b dose search part of this study as of 
16 Dec 2019,7 in the nivolumab arm and 6 in the pembrolizumab arm. Tumor evaluation data 
from select renal cell carcinoma (RCC) and urothelial carcinoma patients indicate preliminary 
signs of antitumor activity in this cohort. Therefore, the Sponsor intends to conduct additional 
evaluation of the effect of DSP-7888 Dosing Emulsion in these 2 disease indications in the Phase 
1b enrichment part. The protocol allows for enrollment of up to 24 patients in the Phase 1b 
portion of the study, and additional patients may be enrolled for further assessment if anti-tumor 
activities are observed in any tumor type. 
4.3.3. 
Nonclinical Studies 
4.3.3.1. 
Primary Pharmacology 
4.3.3.1.1. In Vitro Pharmacology 
Two in vitro pharmacology studies (R-PH-DSP-7888-001 and R-PH-DSP-7888-002) were 
conducted to test the induction of CD8+ T cells that recognize WT1126-134 peptide, WT137-45 


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peptide, and modified WT1235-243 peptide in human peripheral blood mononuclear cells (PBMCs) 
stimulated with a mixture of DSP-7888-K and DSR-127629 (the amino acid sequence of the 
latter compound is the same as that of DSP-7888-H). The mixture elicited CD8+ T cells that 
recognized the synthetic WT1126-134 peptide or the synthetic WT137-45 peptide in HLA-A*02:01+ 
PBMCs, and elicited CD8+ T cells that recognized the synthetic modified WT1235-243 peptide in 
HLA-A*24:02+ PBMCs. In addition, the frequency of HLA-A*03:01- or 
HLA-B*15:01-restricted CD8+ T cells that recognized the synthetic WT1126-134 peptide (in 
PBMCs from patients enrolled in Study BBI-DSP7888-201G) was increased by treatment with 
DSP-7888 Dosing Emulsion. 
4.3.3.1.2. In Vivo Pharmacology 
Two in vivo pharmacology studies (R-PH-DSP-7888-003 and R-PH-DSP-7888-004) were 
conducted to test whether DSP-7888 Dosing Emulsion elicits: (1) HLA-A*02:01-restricted CTLs 
that recognize WT1126-134 peptide or WT37-45 peptides in HLA-A*02:01 transgenic mice, and (2) 
HLA-A*24:02-restricted CTLs that recognize modified WT1235-243 peptide in HLA-A*24:02 
transgenic mice. Another study (R-PH-DSP-7888-005) was conducted to test whether 
DSP-7888-H has the ability to enhance the induction of WT1126-134 peptide-reactive T cells in 
HLA-A*02:01 transgenic mice. 
DSP-7888 Dosing Emulsion elicited HLA-A*02:01-restricted CTLs that recognized the 
synthetic WT1126-134 peptide or the synthetic WT137-45 peptide in HLA-A*02:01 transgenic mice, 
and elicited HLA-A*24:02-restricted CTLs that recognized the synthetic modified WT1235-243 
peptide in HLA-A*24:02 transgenic mice. DSP-7888 Dosing Emulsion including DSP-7888-H 
elicited a greater number of T cells reactive to the synthetic WT1126-134 peptide. 
4.3.3.1.3. Safety Pharmacology 
No dedicated safety pharmacology studies have been conducted with DSP-7888 Dosing 
Emulsion. Safety pharmacology endpoints, including routine clinical observations, respiratory 
rate, blood pressure, electrocardiography, and body temperature were evaluated in the Good 
Laboratory Practices (GLP)-compliant 4-week intermittent (once weekly) intradermal toxicity 
study in cynomolgus monkeys, followed by a 4-week recovery period (Study SBL198-332). In 
that study, there were no clinical findings to indicate effects on behavior, respiratory rate, blood 
pressure, electrocardiogram (ECG) parameters, or body temperature following intradermal 
administration of DSP-7888 Dosing Emulsion. 
4.3.3.2. 
Pharmacokinetics 
The pharmacokinetics (PK) of DSP-7888 Dosing Emulsion were evaluated in the same 
non-rodent (cynomolgus monkey) species used for toxicology studies. Additionally, in vitro 
studies were conducted to assess the stability of DSP-7888-K and DSP-7888-H in human and 
monkey blood. Concentrations were presented as the DSP-7888-K or DSP-7888-H equivalents 
unless otherwise indicated.  
4.3.3.2.1. In Vivo Pharmacokinetics in Monkey 
In vivo studies in monkeys (SBL198-338 and JCL14101436) were conducted to investigate the 
PK of DSP-7888 Dosing Emulsion. Male cynomolgus monkeys (n = 2) were given a single 


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intradermal administration of DSP-7888 Dosing Emulsion at a dose volume of 0.1 mL/site to 
10 different injection sites on the back of each animal (1.0 mL/body; containing 10 mg/body as 
DSP-7888-K, 7.5 mg/body as DSP-7888-H). Plasma concentrations of DSP-7888-K and 
DSP-7888-H were then measured at 0.25, 0.5, 1, 2, 4, 8, and 24 hours postdose. DSP-7888-K 
was detected only 0.25 hours after dosing (27.8 ng/mL) and was below the limit of quantification 
(LoQ) (<20 ng/mL) from 0.5 to 24 hours postdose. DSP-7888-H was also detected only 
0.25 hours after dosing (36.7 ng/mL) and was below the LoQ (<20 ng/mL) from 0.5 to 24 hours 
postdose. 
These results indicated that DSP-7888-K and DSP-7888-H transiently appeared in systemic 
circulation, but the plasma concentrations declined rapidly to below the LoQ following a single 
intradermal administration of DSP-7888 Dosing Emulsion to the monkey. 
4.3.3.2.2. In Vitro Stability in Human and Monkey Blood 
The in vitro stability of DSP-7888-K and DSP-7888-H in human and monkey blood was 
investigated (Study JCL14081377). 
DSP-7888-K and DSP-7888-H (at a final concentration of 20 μg/mL) were incubated at 37°C in 
the blood of both humans and monkeys. The mean half-lives of DSP-7888-K in human and 
monkey blood were 0.14 and 0.11 hours, respectively. The mean half-lives of DSP-7888-H in 
human and monkey blood were 0.10 and 0.18 hours, respectively. 
4.3.3.3. 
Toxicology 
Based on the technical feasibility of replicating the planned clinical dose, dosing schedule, and 
routes of administration of DSP-7888 Dosing Emulsion, the cynomolgus monkey was chosen as 
the species in which to evaluate the potential toxicity of DSP-7888 Dosing Emulsion. 
Additionally, because previously published clinical data with other WT1 peptide vaccines 
(Sakai, 2015; Oka, 2004; Soeda, 2010; Kaida, 2011) described ISRs following repeated 
vaccinations, the cynomolgus monkey was considered an appropriate animal model in which to 
evaluate local skin reactions following repeated injections of DSP-7888 Dosing Emulsion. A 
4-week toxicity study was performed using the intradermal route of administration to evaluate 
potential toxicities, including local skin reactions, of DSP-7888 Dosing Emulsion.  
The objective of this GLP-compliant study (SBL198-332) was to evaluate the toxicity of 
DSP-7888 Dosing Emulsion and assess the reversibility of toxicity observed in the animals when 
DSP-7888 Dosing Emulsion was administered intradermally to cynomolgus monkeys once 
weekly for up to 4 weeks, with a 4-week recovery period (total 5 dose times). Two dose levels 
(low-dose and high-dose) were intradermally administered once weekly: DSP-7888-K 
2.0 mg/body + DSP-7888-H 1.5 mg/body (low-dose group) and DSP-7888-K 10 mg/body + 
DSP-7888-H 7.5 mg/body (high-dose group). 
All animals survived until their scheduled sacrifice. Administration of control dosing emulsion 
and DSP-7888 Dosing Emulsion at both low- and high-dose levels did not result in any 
treatment-related effects on body weight, food consumption, ophthalmologic examination, 
electrocardiography, body temperature, blood pressure, respiratory rate, immunophenotyping in 
peripheral blood, or organ weights. 


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In the high-dose group, during the dosing period, erythema, induration, and crust were observed 
in all males and females; erosion was observed in 1 male and 2 females; and ulcer was observed 
in 1 male and 2 females at dose administration sites. At the fifth injection site, erythema, 
induration, crust, erosion, and/or ulcer were observed in the high-dose group during the recovery 
period. In the low-dose group, erythema and induration were observed in all males and females, 
and crust was observed in 1 male and 2 females at dose administration sites. In the control dosing 
emulsion group, erythema was observed in 2 males and 4 females, and induration was observed 
in all females at the dose administration sites. However, these skin reactions showed a tendency 
toward resolution at the end of the recovery period; injection sites in some animals were treated 
with irrigation, disinfection, antibiotics, and/or gauze to prevent secondary infection. 
Alterations in hematology parameters (high platelet count, high fibrinogen levels) and/or blood 
chemistry (high C-reactive protein [CRP], high globulin concentration, low albumin 
concentration, and/or low albumin/globulin ratio) were noted in the animals in the high-dose 
group; erosion and/or ulcer at the injection site were concurrently observed in these animals. 
Based on the results, the alterations in hematology and/or blood chemistry parameters were 
concluded to be secondary to inflammatory changes at the injection site. The alterations were 
fully resolved by the end of recovery period. 
Positive occult blood reaction in urine during the dosing and recovery period, and an increase in 
osmotic pressure during the dosing period were noted in females in the high-dose group in 
urinalysis; however, the findings were not considered to be adverse since they were not 
accompanied by any histopathologic lesions in the kidneys. 
At necropsy, induration at the injection site in the control dosing emulsion and in the low-dose 
and the high-dose groups, erythema and crust at the injection site in the low- and the high-dose 
groups, ulcer and edema in the subcutaneous tissue at the injection site, and erosion at the 
injection site in the high-dose group were observed in males and/or females at the final dose of 
the dosing and/or recovery periods. In the high-dose group, edema in the subcutaneous tissue 
was observed at the fifth injection site at the end of the dosing period, although that finding was 
not observed at the first, second, third, or fourth injection site. At the end of the recovery period, 
edema in the subcutaneous tissue was not observed at any injection site in the high-dose group. 
Additionally, in the high-dose group, enlargement of the axillary lymph nodes in one male and 
inguinal lymph nodes in one female were observed at the end of the dosing period, whereas that 
finding was not noted at the end of recovery period. 
In histopathology, oil droplet, lymphocyte/plasma cell infiltration, macrophage/giant cell 
infiltration, and/or neutrophil infiltration in the dermis/subcutis, and crust in the control dosing 
emulsion, the low-dose, and the high-dose groups; thickening of the epidermis, erosion/ulcer, 
edema in the dermis/subcutis, bulla in the epidermis in the low-dose and the high-dose groups; 
and fibrosis in the dermis and hemorrhage in the subcutis in the high-dose group were observed 
in the injection sites at the end of the dosing and recovery periods. In the high-dose group, at the 
end of dosing period, very slight to moderate edema in the dermis/subcutis and/or bulla in the 
epidermis were observed at the fourth and fifth injection sites, although these findings were not 
noted at the first, second, or third injection sites. At the end of recovery period, edema in the 
dermis/subcutis and bulla in the epidermis were not observed at any injection site except that 
slight edema in the dermis/subcutis was observed at the second injection site.  


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Based on the results, it is considered that the findings in clinical signs, hematology, blood 
chemistry, necropsy, and histopathology related to inflammatory changes at the injection site 
were fully or partially resolved. Oil droplet, lymphocyte/plasma cell infiltration, 
macrophage/giant cell infiltration, and/or neutrophil infiltration were observed in the sinus and/or 
the capsule in the axillary and/or inguinal lymph nodes in the control dosing emulsion, the 
low-dose, and/or the high-dose groups. No changes, except for those at the injection sites or in 
the lymph nodes, were noted in any organs or tissues in the DSP-7888 Dosing Emulsion-treated 
groups. 
Under the conditions of this study, the no-observed adverse effect level (NOAEL) of DSP-7888 
Dosing Emulsion was not determined. The highest non-severely toxic dose (HNSTD) was 
declared as the high dose of DSP-7888 Dosing Emulsion (DSP-7888-K 10 mg/body + 
DSP-7888-H 7.5 mg/body). 
4.3.4. 
Clinical Studies 
DSP-7888 Dosing Emulsion is being evaluated in 3 clinical studies in patients with advanced 
malignancies: Studies DB650027 and DB601001 in Japan and Study BBI-DSP-7888-201G 
under an IND in the US and under CTAs in other countries. One study has been completed, 
study BBI-DSP-7888-101, in patients with advanced malignancies. No deaths have been 
attributed to DSP-7888 Dosing Emulsion in the completed and ongoing clinical studies. Injection 
site reaction is the most common AE of DSP-7888 Dosing Emulsion identified in the clinical 
studies (see Section 8.3.5 regarding management of the ISRs). 


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5. 
STUDY OBJECTIVES AND ENDPOINTS 
A summary of objectives, endpoints, and assessments of the study is presented in Table 3 below. 
Table 3: 
Study Objectives, Endpoints, and Assessments 
Phase 1b 
 
Objectives 
Endpoints 
 
Phase 1b  
Primary 
Objective 
To evaluate the safety and 
tolerability, and identify a 
recommended intradermal dose of 
DSP-7888 Dosing Emulsion in 
combination with nivolumab or 
pembrolizumab 
1. Incidence of DLTs, except for those 
patients treated in the enrichment cohort 
2. Incidence and severity of AEs, serious 
AEs (SAEs)  
3. Dose interruption, reduction, and dose 
intensity  
Secondary 
Objective 
To evaluate the preliminary 
antitumor activity of DSP-7888 
Dosing Emulsion in combination 
with nivolumab and pembrolizumab 
in terms of ORR, disease control rate 
(DCR), duration of response (DOR), 
6-month progression-free survival 
(PFS) Rate, overall survival (OS) 
1. ORR, defined as proportion of patients 
who have achieved confirmed complete 
response (CR) or partial response (PR), 
evaluated using Response Evaluation 
Criteria in Solid Tumors (RECIST) 
(v.1.1) and immune RECIST (iRECIST) 
based on investigator assessment 
2. DCR, defined as the percentage of 
patients who have achieved best overall 
response (BOR) of CR, PR, or stable 
disease (SD) per RECIST (v.1.1) and 
iRECIST 
3. DOR, defined as the time from the first 
documentation of a response (CR or PR) 
until time of first documentation of 
disease progression by RECIST (v.1.1) 
and iRECIST, or death by any cause 
4. PFS, defined as the time from the date of 
the first dose of study treatment to the 
earlier date of assessment of progression 
by RECIST (v.1.1) and iRECIST, or 
death by any cause  
5. 6-month PFS Rate, defined as the 
proportion of patients who neither 
progressed by RECIST (v.1.1) and 
iRECIST nor died before 6 months (24 
weeks) from the first study treatment 
6. OS, defined as the time from the date of 
the first dose of study treatment to the 
date of death by any cause 


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Objectives 
Endpoints 
 
Exploratory 
Objective 
To characterize pharmacodynamic 
(PD) or potential predictive 
biomarkers and their relationship to 
clinical activity 
Biomarkers using peripheral blood samples 
and tumor tissue samples in patients receiving 
DSP-7888 Dosing Emulsion in combination 
with pembrolizumab may be evaluated for 
correlation with the following immunologic 
changes and/or clinical responses 
1. WT1-specific CTL induction activity in 
blood samples 
2. WT1 expression level via chromogenic in 
situ hybridization (CISH) and PD-L1 
expression level via 
immunohistochemistry (IHC) 
3. CD8+ cell density in tumor tissues  
4. Tumor infiltrating lymphocytes (TILs) 
profiling in tumor tissues 
5. Immune profiling in tumor tissues with 
tumor inflammation signature analysis   
6. Mutation status and tumor mutation 
burden (TMB) in tumor tissues 
 
To determine the PFS rate as an 
evaluation of treatment benefit of 
DSP-7888 Dosing Emulsion 
administered with nivolumab or 
pembrolizumab 
PFS rate is defined as PFS1/PFS (-1) ratio 
using RECIST (v.1.1)  
1. PFS1 is defined as the time from the date 
of the first dose of study treatment to the 
earlier date of assessment of progression 
by RECIST (v.1.1), or death by any cause 
2. PFS (-1) is defined as the date of initiation 
of the previous (penultimate) treatment 
regimen to the date of assessment of 
progression by RECIST (v.1.1) 
Abbreviations: AEs = adverse events; CTL = cytotoxic T lymphocyte; DCR = disease control rate; DOR = duration 
of response; IHC = immunohistochemistry; iRECIST = Immune Response Evaluation Criteria In Solid Tumors; 
ORR = objective response rate; OS = overall survival; PFS = progression-free survival; RECIST = Response 
Evaluation Criteria In Solid Tumors; SAEs = serious adverse events; TIL = tumor-infiltrating lymphocytes; 
TMB = tumor mutation burden; WT1 = Wilms Tumor 1 
*Note: It should be ensured that 8 to 23 slides of archival samples and/or the equivalent amount of archival tissue 
block and/or fresh biopsy samples from enrolled patients are available at Pre-screening/Screening. From patients 
who consent to providing additional samples by signing the additional informed consent for these optional samples, 
an additional 6 to 8 slides will be collected for future biomarker analysis. These samples must contain sufficient 
tumor tissue. Details of the biopsy time points are described in the schedule of assessments (SOA) in Table 7, 
Table 8, and Table 9.  


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Phase 2 
 
Objectives  
Endpoints 
 
Phase 2 
Primary 
To evaluate the preliminary antitumor 
activity of DSP-7888 Dosing 
Emulsion administered with 
pembrolizumab in terms of ORR in 
patients with platinum-resistant 
ovarian cancer (PROC) 
ORR, defined as the proportion of patients 
who have achieved confirmed CR or PR, 
evaluated using RECIST (v.1.1) based on 
investigator assessment 
Secondary 
To evaluate the preliminary clinical 
activity of DSP-7888 Dosing 
Emulsion in combination with 
pembrolizumab in terms of DOR, 
DCR, PFS, 6 months PFS Rate, and 
OS of DSP-7888 Dosing Emulsion 
administered in combination with 
pembrolizumab in PROC 
1. 
DOR, defined as the time from the first 
documentation of a response (CR or PR) 
until time of first documentation of 
disease progression by RECIST (v.1.1), 
or death by any cause 
2. 
DCR, defined as the percentage of 
patients who have achieved BOR of CR, 
PR, or SD per RECIST (v.1.1)   
3. 
PFS, defined as the time from the date of 
the first dose of study treatment to the 
earlier date of assessment of progression 
by RECIST (v.1.1), or death by any 
cause  
4. 
6 months PFS Rate, defined as the 
proportion of patients who neither 
progressed by RECIST (v.1.1) nor died 
before 6 months (24 weeks) from the 
first study treatment 
5. 
OS, defined as the time from the date of 
the first dose of study treatment to the 
date of death by any cause 
To determine ORR, DCR, PFS, and 
iDOR per iRECIST of DSP-7888 
Dosing Emulsion administered in 
combination with pembrolizumab in 
PROC 
1. immune ORR (iORR), defined as 
proportion of patients who have achieved 
confirmed immune complete response 
(iCR) or immune partial response (iPR), 
evaluated using iRECIST based on 
investigator assessment  
2. immune DCR (iDCR), defined as the 
percentage of patients who have achieved 
BOR of iCR, iPR, or iSD per iRECIST 
3. immune PFS (iPFS), 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 


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Objectives  
Endpoints 
 
4. immune DOR (iDOR), defined as the time 
from the first documentation of response 
(iCR or iPR) until time of first 
documentation of disease progression by 
iRECIST, or death by any cause 
* The event date to be used for calculation of 
PFS should be the first date at which 
progression criteria are met (ie, the date of 
immune unconfirmed progressive disease 
[iUPD]) provided that immune confirmed 
progressive disease [iCPD] is confirmed at the 
next assessment. If iUPD occurs, but is 
disregarded because of later iSD, iPR, or iCR, 
that iUPD date should not be used as the 
progression event date 
To evaluate the safety and tolerability 
of DSP-7888 Dosing Emulsion 
administered with pembrolizumab 
Frequency and intensity of AEs using 
Common Terminology Criteria for Adverse 
Events (CTCAE) v 4.03 
Exploratory To determine the PFS rate as an 
evaluation of treatment benefit of 
DSP-7888 Dosing Emulsion 
administered with pembrolizumab 
PFS rate is defined as PFS1/PFS (-1) ratio 
using RECIST (v.1.1)  
1. PFS1 is defined as the time from the date 
of the first dose of study treatment to the 
earlier date of assessment of progression 
by RECIST (v.1.1), or death by any cause 
2. PFS (-1) is defined as the date of initiation 
of the previous (penultimate) treatment 
regimen to the date of assessment of 
progression by RECIST (v.1.1) 
To evaluate the antitumor activity of 
DSP-7888 Dosing Emulsion 
administered with pembrolizumab in 
terms of the CA-125 response rate 
and time to progression with CA-125 
criteria in PROC 
1. CA-125 response rate is defined as 
proportion of patients who have achieved 
response using the Gynecologic Cancer 
InterGroup (GCIG) CA-125 response 
definition 
2. Time to progression with CA-125 is 
defined as the time from the date of the 
first dose of study treatment to the earlier 
date of assessment of progression by 
GCIG CA-125 progression definition or 
death by any cause 
To characterize PD or potential 
predictive biomarkers and their 
relationship to clinical activity 
Biomarkers using peripheral blood samples 
and tumor tissue samples in patients receiving 
DSP-7888 Dosing Emulsion in combination 
with pembrolizumab may be evaluated for 
correlation with the following immunologic 
changes and/or clinical responses 


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Objectives  
Endpoints 
 
1. WT1-specific CTL induction activity in 
blood samples  
2. WT1 expression level via CISH and PD-
L1 expression status (CPS) via IHC in 
tumor tissue 
3. CD8+ cell density in tumor tissues  
4. TILs profiling in tumor tissues  
5. Immune profiling in tumor tissues with 
tumor inflammation signature analysis   
6. Mutation status and mutational burden 
analysis in tumor tissues  
7. HLA typing 
*Note: These samples must contain sufficient tumor tissue. Details of the biopsy time points are described in the 
SOA in Table 7, Table 8, and Table 9. 


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6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
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: Phase 1b (a dose search part and an enrichment part) and 
Phase 2 dose expansion (Figure 2). In the Phase 1b part 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, a Phase 1b enrichment cohort of a further 10 patients, who have locally advanced or 
metastatic renal cell carcinoma (RCC) or urothelial cancer with primary or acquired resistance to 
previous checkpoint inhibitors, will be enrolled and will be dosed with DSP-7888 Dosing 
Emulsion and nivolumab, or DSP-7888 Dosing Emulsion and pembrolizumab, as per the 
investigator’s preference. The purpose of this Phase 1b enrichment cohort is to help evaluate the 
preliminary antitumor activity of DSP-7888 Dosing Emulsion at the safe dose level identified in 
the Phase 1b dose search part.  
Once the recommended dose is determined in the Phase 1b dose search part, PROC patients will 
be enrolled in the Phase 2 part of the study with DSP-7888 Dosing Emulsion, exploring the 
combination with pembrolizumab. In Phase 2, a total of approximately 40 patients with PROC 
will be enrolled. 
Objective disease assessments will be performed according to Table 7 (Phase 1b Arm 1), 
Table 8, (Phase 1b Arm 2), and Table 9 (Phase 2). 
Figure 2: 
Overall Study Design  
 
 
Note: The DSP-7888 Dosing Emulsion 3.5 mg + a PD-1 inhibitor cohort will only open if >1 out of 6 patients from 
the DSP-7888 Dosing Emulsion 10.5 mg + a PD-1 inhibitor cohort report a DLT. 
Phase 1b: Safety and recommend dose
DSP-7888
10.5 mg
+a PD-1 Ab
Phase 2: Dose Expansion Phase for efficacy
DSP-7888
3.5 mg
+a PD-1 Ab
DLT > 1/6
Arm 1: combination with Nivolumab 240 mg (n=6-12)
Arm 2: combination with Pembrolizumab 200 mg (n=6-12)
Phase 1b Enrichment Cohort
Additional 10 patients with RCC/Urothelial cancer who 
were resistant to previous ICI therapy
DSP-7888
10.5 mg
Pembrolizumab 
200 mg
Platinum Resistant 
Ovarian Cancer
DLT
1
2
3
N=40* 
*Additional patients may be 
enrolled to further assess anti-
tumor activities in the 
subgroups of interest. 
However, the total sample size 
of Phase 2 part cannot exceed 
60 patients.


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6.1.1. 
Phase 1b 
6.1.2. 
Dose Search Part 
After providing written informed consent, patients will undergo screening assessments, which 
will include a careful review of each patient’s medical history. 
Patients will be administered doses of DSP-7888 Dosing Emulsion intradermally in both arms of 
the study (Arm 1 and Arm 2). Arm 1 will include patients with indications approved by the 
Health Authorities for treatment with nivolumab: advanced melanoma, non-small cell lung 
cancer (NSCLC), RCC, urothelial carcinoma, head and neck squamous cell carcinoma 
(HNSCC), hepatocellular carcinoma (HCC), and microsatellite instability-high or mismatch 
repair-deficient (MSI H/dMMR) colorectal cancer. Arm 2 will include patients with indications 
approved by the Health Authorities for treatment with pembrolizumab: melanoma, NSCLC, 
HNSCC, urothelial carcinoma, MSI-H/dMMR cancer, gastric cancer or gastroesophageal 
junction adenocarcinoma, and cervical cancer (Figure 3). 
In the Phase 1b dose search part of the study, during the Arm 1 induction phase (4 weeks), 
DSP-7888 Dosing Emulsion will be administered once weekly for 4 weeks, with nivolumab 
administered every other week. In the subsequent Arm 1 maintenance phase, DSP-7888 Dosing 
Emulsion will be administered once every 2 weeks with nivolumab until a discontinuation 
criterion is met. Arm 2 will include patients with indications approved by the Health Authorities 
for treatment with pembrolizumab: melanoma, NSCLC, HNSCC, urothelial carcinoma, 
MSIH/-dMMR cancer, gastric cancer or gastroesophageal junction adenocarcinoma, and cervical 
cancer. During the Arm 2 induction phase (6 weeks), DSP-7888 Dosing Emulsion will be 
administered once weekly for 6 weeks, with pembrolizumab administered once every 3 weeks. 
In the subsequent Arm 2 maintenance phase, DSP 7888 Dosing Emulsion will be administered 
once every 3 weeks with pembrolizumab until a discontinuation criterion is met. 
Both programmed cell death-1 (PD-1) inhibitors (nivolumab and pembrolizumab) will be 
administered in the approved dose and schedule starting on Day 1 of the study. Study sites will 
not be limited to any arm of the study, and each arm will investigate the recommended dose in 
parallel.  
The Phase 1b dose search part of the study is completed, and no further patients will be 
enrolled under the dosing regimen described above (this legacy regimen is also depicted in 
Appendix 8). For patients enrolled under the Phase 1b enrichment part of the study, the 
dosing regimen described below will be followed per Amendment 5 of the protocol. 
6.1.3. 
Enrichment Part 
The Phase 1b enrichment cohort (consisting of the additional 10 patients) will include patients 
with locally advanced or metastatic RCC or urothelial carcinoma who experienced disease 
progression per iRECIST (immune confirmed progressive disease [iCPD]) during or within 
3 months of last dose of the most recent prior anti-PD-1/PD-L1-based treatment.  
Patients will be treated with the combination of DSP-7888 Dosing Emulsion and nivolumab, or 
DSP 7888 Dosing Emulsion and pembrolizumab, as per the treating physician’s choice.  


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The administration of DSP-7888 Dosing Emulsion and anti-PD1 therapy in the Phase 1b 
enrichment cohort will differ from that in the Phase 1b dose search part of the study, and will be 
staggered as follows: 
Arm 1 (Enrichment Cohort Only): DSP-7888 + nivolumab combination: 
• DSP-7888 Dosing Emulsion will start on Day 1, Q1W for first 4 weeks, then Q2W 
thereafter 
• Nivolumab will start on Day 1 of Cycle 3 (Day 29), Q2W 
Arm 2 (Enrichment Cohort Only): DSP-7888 + pembrolizumab combination: 
• DSP-7888 Dosing Emulsion will start on Day 1, Q1W for first 3 weeks, then Q3W 
thereafter 
• Pembrolizumab will start on Day 1 of Cycle 2 (Day 22), Q3W 
6.1.4. 
Phase 2 
A Phase 2, multicenter, open-label, single-arm, study will be conducted to evaluate the efficacy 
and safety of DSP-7888 Dosing Emulsion in combination with pembrolizumab in patients with 
advanced high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who 
were previously treated with platinum-based therapy and experienced resistance to 
platinum-based therapy, defined as patient relapsed within 6 months after last dose of 
platinum-based therapy. Patients must have received 1 to 4 previous treatment regimens.  
The Phase 2 dose of DSP-7888 Dosing Emulsion will be the recommended dose as determined 
in the Phase 1b Arm 2 part of the study.  
Approximately 40 eligible PROC patients are expected to be enrolled in the Phase 2 dose 
expansion part of the study.  
For patients enrolled under Protocol Amendment 4, the administration of DSP-7888 Dosing 
Emulsion and anti-PD1 in the Phase 2 dose expansion cohort is the same as that in the Phase 1b 
Arm 2 of the dose search part. For patients enrolled under Protocol Amendment 5, administration 
of DSP-7888 Dosing Emulsion and anti-PD1 will be staggered as follows: 
DSP-7888 + pembrolizumab combination: 
• DSP-7888 Dosing Emulsion will start on Day 1, Q1W for first 3 weeks, then Q3W 
thereafter 
• Pembrolizumab will start on Day 1 of Cycle 2 (Day 22), Q3W 
6.1.4.1. 
Duration of Treatment 
The study consists of 4 periods: Prescreening period, Screening period, Treatment period, and 
Follow-up period (See Appendix 7). 
Each patient will participate in the trial from the time the patient signs the Prescreening informed 
consent form (ICF) until completion of survival follow-up (see Figure 2).  
Human leukocyte antigen (HLA)-eligible patients in the Prescreening period will move on to a 
Screening period within a 28-day window from Cycle 1 Day1. Following Screening, all eligible 


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patients will receive treatment of DSP-7888 Dosing Emulsion in combination with 
pembrolizumab or nivolumab, dependent upon phase of the study.  
For those patients enrolled under Protocol Amendment 5, DSP-7888 Dosing Emulsion will start 
on Day 1, pembrolizumab will start on Day 1 of Cycle 2 (Day 22), and then once every 3 weeks 
thereafter until the patient completes 35 cycles (approximately 24 months) of study treatment (if 
the patient is experiencing clinical benefit, and in the opinion of the investigator it is in the 
patient’s best interest to continue the study beyond 35 cycles, the patient may continue treatment 
after documented discussion with the Sponsor). Reasons for treatment discontinuation are 
described in Section 7.3.1. 
Once patients discontinue or complete treatment, they will enter the follow-up period including 
disease assessment follow-up for any patient who discontinues study treatment for a reason other 
than immune confirmed PD (iCPD), and/or survival follow-up. 
6.1.4.2. 
Prescreening Period 
After signing the HLA screening ICF, patients will be evaluated for HLA subtype eligibility. 
Blood samples must be submitted to a centralized laboratory for HLA testing to determine 
patient eligibility for enrollment into the study. Patients found to be HLA eligible will move on 
to participate in further screening assessments for the complete evaluation of all other study 
eligibility criteria. Patients may proceed with the HLA screening ICF and HLA test while still 
receiving the prior therapy. 
6.1.4.3. 
Screening Period 
A Screening period will start once the patient signs the main ICF, and all procedures should be 
completed within 28 days from Cycle 1 Day 1. In the Screening period, patient eligibility will be 
determined based on the eligibility criteria, and patients will undergo screening assessments 
according to the Schedule of Assessments (SOA). Tissue samples (fresh or archival) will be 
required for exploratory biomarker analysis. Post-treatment biopsies are requested per SOA, 
unless collecting the tumor biopsy is determined to be not medically feasible by the treating 
investigator.   
6.1.4.4. 
Treatment Period 
Per Amendment 5, the treatment period consists of 2 treatment phases: Induction phase and 
Maintenance phase. 
1. Induction phase (First cycle) 
• DSP-7888 Dosing Emulsion 10.5 mg intradermal injection, once weekly (Q1W), 
Days 1, 8, and 15 of Cycle 1 
2. Maintenance phase (All cycles after Cycle 1 up to Cycle 35) 
• DSP-7888 Dosing Emulsion 10.5 mg intradermal injection, Day 1 of Cycle 2 (Q3W) 
and each subsequent cycle 
• Pembrolizumab 200 mg IV infusion Day 1 of Cycle 2 (Q3W) and each subsequent 
cycle until discontinuation or up to Cycle 35 


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On the days when both DSP-7888 Dosing Emulsion and pembrolizumab are administered, 
DSP-7888 Dosing Emulsion should be administered first. Study treatment may be modified for 
AEs per dose modification guidelines or based on the clinical judgment of the treating 
investigator. 
Patients will be asked to undergo study specific visits and procedures according to SOA. Patients 
will be evaluated for objective response to study drug treatment with radiographic imaging 
(computer tomography [CT] scan or magnetic resonance imaging [MRI]) using RECIST (v.1.1) 
every 6 weeks for 24 weeks, and then every 12 weeks until progression. If a patient experiences 
objective disease progression according to RECIST (v 1.1) and is clinically stable, the patient 
will continue on treatment with study drug until the patient experiences iCPD per iRECIST. 
Clinical stability is defined as: 
• No worsening of performance status 
• No clinically relevant increase in disease-related symptoms 
• No requirement for intensified management of disease-related symptoms (such as 
analgesics, radiation, or palliative care)  
Patients who remain on study treatment following objective disease progression per RECIST 
(v.1.1) will continue to be evaluated for objective response to study treatment according to the 
SOA and to iRECIST. 
Patients also will be monitored for serum CA-125 using GCIG CA-125 criteria as part of clinical 
evaluation of response according to the SOA. Progressive disease may not be determined by 
CA-125 progression alone.  
Adverse event monitoring will be ongoing throughout the study and graded in severity according 
to the guidelines outlined in the National Cancer Institute (NCI) CTCAE version 4.03. Patients 
will be evaluated for AEs from the time of signing the main ICF until 30 days after their last 
dose of study treatment.  
Blood samples will be required for safety labs, CA-125 assessment, as well as the biomarker 
assay during the treatment period, and a fresh tumor tissue sample is requested post-treatment for 
biomarker assessment if medically feasible. 
6.1.4.5. 
Follow-up Period 
The follow- up period will begin once a patient has discontinued study treatment. Follow-up 
period includes disease assessment follow-up (for patients who discontinue study treatment for a 
reason other than iCPD per iRECIST) and survival follow-up. 
Patients who discontinue study treatment without experiencing iCPD will continue to undergo 
tumor assessment and evaluation of CA-125 (Phase 2), according to the SOA until up to 
24 months after last dose of study drug, the start of new anticancer therapy, iCPD per iRECIST, 
death, loss to follow-up, withdrawal of consent, or the end of the study, whichever occurs first. 
Patients who discontinue study treatment when experiencing iCPD per iRECIST with study 
drug, or patients who discontinue study treatment without experiencing iCPD per iRECIST, but 
who experience iCPD per iRECIST or start new anticancer therapy during disease follow-up will 
be assessed for survival and new anticancer treatment status per the SOA, until up to 24 months 


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after the last dose of study drug, death, withdrawal of consent, loss to follow-up, or end of the 
study, whichever occurs first.  
The safety and tolerability of DSP-7888 Dosing Emulsion in combination with immunotherapy 
PD-1 inhibitors will be assessed for the duration of study treatment and follow-up (see Table 7, 
Table 8, and Table 9 for the respective SOAs). 
All AEs will be collected and recorded for each patient from the date of signing the main ICF for 
the study until 30 days after last study drug administration. Any pregnancies that occur within 
180 days after last study drug administration are to be captured. An AE will be followed until it 
is either resolved, has returned to baseline, or is determined to be a stable or chronic condition 
(see Table 7, Table 8, and Table 9). 
Particular attention should be given to the follow up of any Grade 3 or higher injection site 
reactions ongoing at the End of Treatment period until resolution, return to baseline, determined 
to be a stable or chronic condition or until the patient is lost to follow up or the patient has died. 
Please record the data within EDC per eCRF instructions. In the instance of resolution with 
sequelae, please be sure to enter the sequelae as a separate AE (eg skin discoloration, persistent 
induration, scarring “from ISR”). To facilitate this careful follow up, please consider use of 
video teleconference with the patient during the follow up period post study. 
Objective disease assessments will be performed according to RECIST and iRECIST. For Phase 
1b, the first assessment will be performed during Cycle 3, at 4 weeks for the nivolumab arm and 
at 6 weeks for the pembrolizumab arm, and at Weeks 12, 18, and 24, after the first dose of 
DSP-7888 Dosing Emulsion. After that, objective disease assessments will occur every 12 weeks 
until patient discontinuation from the study. For Phase 2, patients will be evaluated for objective 
response to study drug treatment with radiographic imaging every 6 weeks for 24 weeks and then 
every 12 weeks until progression.   


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 Figure 3: 
Schematic of Study Arm 1 and Study Arm 2 in Phase 1b 
 
Figure 4: 
Schematic of Phase 2 of Study 
 
6.2. 
Planned Number of Patients 
In Phase 1b of the study, there will be approximately 6 to 12 patients for each arm, up to a total 
of up to 24 patients. In the enrichment cohort, 10 patients will be enrolled. If anti-tumor activities 
are observed in any tumor type, additional patients may be enrolled for further assessment. In 
Phase 2 of the study, approximately 40 patients will be enrolled. Additional patients may be 
enrolled to further assess anti-tumor activities in the subgroups of interest. However, the total 
sample size of Phase 2 cannot exceed 60 patients.  
6.3. 
Treatment Assignment 
6.3.1. 
Phase 1b 
The administration of DSP-7888 Dosing Emulsion and anti-PD1 therapy in the Phase 1b 
enrichment cohort will be staggered as follows: 
1
8
15
22
29
36
43
50
57
64
71
78
85+
Induction  Phase
Nivolumab Dose Day
DSP-7888 Dosing Emulsion Dose Day
Arm 1: DSP-7888 Dosing Emulsion plus Nivolumab
1
8
15
22
29
36
43
50
57
64
71
78
85+
Maintenance  Phase
DSP-7888
10.5 mg
Nivolumab
240 mg
1
8
15
22
29
36
43
50
57
64
71
78
85+
Induction  Phase
Pembrolizumab Dose Day
DSP-7888 Dosing Emulsion Dose Day
1
8
15
22
29
36
43
50
57
64
71
78
85+
Maintenance  Phase
DSP-7888
10.5 mg
Pembrolizumab
200 mg
Arm 2: DSP-7888 Dosing Emulsion plus Pembrolizumab
PROC 
patients
N~40-60
HLA prescreening
Enrichment strategy
•
Additional patients may be enrolled to 
further assess anti-tumor activities in the 
subgroups of interest 
•
Total sample not to exceed 60 patients


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Arm 1 (Enrichment Cohort Only): DSP-7888 + nivolumab combination: 
• DSP-7888 Dosing Emulsion 10.5 mg will start on Day 1, Q1W for first 4 weeks, then 
Q2W thereafter 
• Nivolumab 240 mg will start on Day 1 of Cycle 3 (Day 29), Q2W 
Arm 2 (Enrichment Cohort Only): DSP-7888 + pembrolizumab combination: 
• DSP-7888 Dosing Emulsion 10.5 mg will start on Day 1, Q1W for first 3 weeks, then 
Q3W thereafter 
• Pembrolizumab 200 mg will start on Day 1 of Cycle 2 (Day 22), Q3W 
Patients in this study will receive DSP-7888 Dosing Emulsion at assigned dose levels, according 
to Table 4 and Table 6 and according to the study arm. Each study arm will begin at Dose Level 
I, and dose de-escalation will proceed independently of the other arms if a safety concern occurs 
in Dose Level I. For a given patient, the appropriate PD-1 combination partner will be 
determined by the treating investigator (see Table 5) for dose schedule. Dose adjustments of 
DSP-7888 Dosing Emulsion are allowed as per protocol. As per their labels and package inserts, 
dose adjustments for nivolumab and pembrolizumab are not recommended. 
The Phase 1b enrichment cohort (10 patients) will be treated with the combination of DSP-7888 
Dosing Emulsion and nivolumab, or DSP-7888 Dosing Emulsion and pembrolizumab, as per the 
treating physician’s choice, following the dosing guidelines and schedule stated above in this 
section.  
For an individual patient, the combined treatment of DSP-7888 Dosing Emulsion and nivolumab 
or DSP-7888 Dosing Emulsion and pembrolizumab will continue until the investigator 
determines that the patient is no longer likely to receive clinical benefit from DSP-7888 Dosing 
Emulsion. However, to assess the benefit of radiologic imaging in accordance with the iRECIST 
criteria, in cases of suspected progression, the protocol requires a confirmatory scan performed 
4 to 8 weeks following the initial scan that shows the suspected progression. 
Patients will continue to receive study treatment independent of radiologic assessment or 
progression: 
1. Provided that the investigator considers it to be safe for the patient 
2. Provided that the investigator determines that there is potential benefit for the patient 
3. When the patient is willing to continue 


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Table 4: 
Phase 1b Study Dose Level and Schedule 
DSP-7888 Dosing Emulsion Dose 
Level 
 
DSP-7888 Dosing Emulsion Dose and Schedule 
DSP-7888 Dosing Emulsion Dose 
Level I 
Nivolumab Arm (Arm 1): 10.5 mg weekly for 4 weeks for induction phase, 
then every 2 weeks for maintenance phase  
Pembrolizumab Arm (Arm 2): 10.5 mg weekly for 3 weeks for induction 
phase, then every 3 weeks for maintenance phase  
DSP-7888 Dosing Emulsion Dose 
Level II 
Nivolumab Arm (Arm 1): 3.5 mg weekly for 4 weeks for induction phase, 
then every 2 weeks for maintenance phase 
Pembrolizumab Arm (Arm 2): 3.5 mg weekly for 3 weeks for induction 
phase, then every 3 weeks for maintenance phase  
DSP-7888 Dosing Emulsion Dose 
Level III 
Nivolumab Arm (Arm 1): 1.75 mg weekly for 4 weeks for induction 
phase, then every 2 weeks for maintenance phase  
Pembrolizumab Arm (Arm 2): 1.75 mg weekly for 3 weeks for induction 
phase, then every 3 weeks for maintenance phase 
 
Table 5: 
PD-1 Inhibitor Dose 
PD1 Inhibitor 
Dose and Schedule 
Nivolumab  
In Arm 1, 240 mg administered intravenously (IV) over 30 minutes (±5)* 
every 14 days (2 weeks/cycle) starting from Day 1 of Cycle 3 (Day 29), 
then maintenance phase (after Cycle 3). 
Pembrolizumab 
In Arm 2, 200 mg/8 mL administered through IV infusion over 30 (±5) 
minutes every 21 days (3 weeks) starting from Day 1 of Cycle 2 (Day 22), 
then maintenance phase (after Cycle 2).  
*The administration time change from 60 to 30 minutes is based on the updated dosage and administration guidance of the new 
nivolumab product label released in July 2018.   
6.3.2. 
Phase 2 (Dose-Expansion Part)  
Patients will have access to study treatment as long as they are benefiting from study treatment 
or have received up to a total of 35 treatment cycles (approximately 105 weeks). Patients may 
continue the study treatment beyond 35 treatment cycles if the patient is experiencing clinical 
benefit, after documented discussion with the Sponsor. 
DSP-7888 Dosing Emulsion and pembrolizumab will be administered at the recommended dose 
level from the Phase 1 part of the study, following the same schedule as listed in Table 6.   
Table 6: 
Phase 2 Study Dosing Schedule  
Investigational 
Product 
Frequency 
Dosage  
Route of 
Administration 
DSP-7888 Dosing Emulsion 
Q1W for first 3 weeks 
Q3W post 3 weeks 
10.5mg 
Intradermal injection 
(ID) 
Pembrolizumab 
Q3W, starting from Day 
1 of Cycle 2 (Day 22) 
Solution for infusion 
200mg/8mL 
IV infusion  


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6.4. 
Dose-limiting Toxicities (Phase 1b Dose Search Part Only) 
A dose-limiting toxicity (DLT) is defined by the occurrence of 1 of the toxicities defined below, 
occurring during the first 28 days of Arm 1 (DSP-7888 Dosing Emulsion induction phase in 
combination with nivolumab; Arm 1) and the first 42 days of Arm 2 (DSP-7888 Dosing 
Emulsion induction phase in combination with pembrolizumab; Arm 2).  
Evaluable patients are defined per Dose-Determining Set (DDS), as defined in Section 12.1.2.3. 
Patients who discontinue before meeting the DDS criteria may be replaced to fully evaluate a 
given dose level. The criteria for the determination of DLT will apply to a given administration 
schedule independently. 
No intrapatient dose escalation/de-escalation is allowed during the DLT evaluation period. 
The following treatment-related AEs will be considered a DLT: 
Non-hematologic 
• Any treatment-related Grade 3 or higher non-hematologic clinical (non-laboratory) 
AE, with the following exceptions: 
− Grade 3 nausea/vomiting or Grade 4 vomiting that resolves to Grade 1 or 2 in 
72 hours or less with appropriate supportive care 
− Grade 3 or 4 diarrhea that resolves to Grade 1 or 2 in 72 hours or less with 
appropriate supportive care 
− Grade 3 fatigue lasting <5 days 
− Grade 3 hypertension that can be controlled with medical therapy within 7 days 
• Any treatment-related Grade 3 or higher non-hematologic laboratory abnormality if: 
− Medical intervention is required to treat the patient, or 
− The abnormality leads to hospitalization, or 
− The abnormality persists for ≥7 days 
Hematologic 
• Any treatment-related hematologic toxicity specifically defined as:  
− Thrombocytopenia Grade 4 or higher, or Grade 3 associated with bleeding  
− Neutropenia Grade 4 for ≥7 days, or Grade 3 or 4 associated with infection or 
febrile neutropenia  
− Anemia Grade 4, or Grade 3 or 4 requiring blood transfusion 
Immune-related 
• Grade 3 or higher CTCAE v. 4.03 immune system disorder-related adverse reactions 
that persist as Grade 3 for >14 days, despite appropriate treatment, except for allergic 
reactions and autoimmune reaction 
• Any Grade 3 or higher allergic reaction 


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• Any Grade 2 or higher autoimmune reaction with the following exceptions:  
− Grade 2 elevation of transaminases/hepatitis that recovers to Grade 0 or 1 within 
10 days (for patients with liver metastases, elevation of transaminases due to 
hepatitis that recovers to baseline within 10 days) 
− Grade 2 hypothyroidism that recovers to Grade 0 or 1 within 7 days without 
steroids 
− Grade 2 diarrhea/colitis that spontaneously recovers to Grade 0 or 1 within 7 days 
with supportive care but without steroids 
− Grade 2 immune-related rash/dermatitis 
• Any treatment-related Grade 4 ISR or Grade 3 ISR that requires hospitalization. 
Any patient who experiences a DLT should be permanently removed from study treatment and 
should not be replaced. 
Note that DSP-7888 Dosing Emulsion dosing has been managed with dose interruptions and/or 
adjustments for ISRs/AEs. Therefore, a DSP-7888 Dosing Emulsion dose interruption/delay for 
an AE related to an ISR that does not meet a DLT definition, as described above, will be 
considered a non-DLT modification. Non-DLT dose modifications will not be considered in 
determining the recommended dose for DSP-7888 Dosing Emulsion; however, they will be 
considered in determining further management of the DSP-7888 Dosing Emulsion dosing 
schedule in the expansion part, in combination with the selected PD-1 inhibitor. 
6.5. 
Defining Recommended Dose of DSP-7888 Dosing Emulsion with 
Nivolumab or Pembrolizumab (Only Phase 1b Dose Search Part) 
The determination of the recommended dose of DSP-7888 Dosing Emulsion in combination with 
nivolumab or pembrolizumab will be based on the criteria defined herein.  
Initially, 6 patients will be enrolled into each of the arms according to a rolling 6 study design at 
the DSP-7888 Dosing Emulsion Dose Level I (of 10.5 mg weekly) in combination with either 
nivolumab 240 mg (every 2 weeks; Arm 1) or pembrolizumab 200 mg (every 3 weeks; Arm 2).   
The recommended dose of DSP-7888 Dosing Emulsion in combination with a given PD-1 
inhibitor agent will be determined in each study arm. Dose adjustments will proceed 
independently in each study arm. The recommended dose of DSP-7888 Dosing Emulsion must 
be less than or equal to a dose level at which 1 out of 6 patients enrolled experience a DLT (see 
definition of a DLT in Section 6.4). A dose level is eligible for consideration as the 
recommended dose if 0 or 1 of 6 patients enrolled experience a DLT at that dose level.   
Criteria for determining whether a given dose level is eligible to be considered a recommended 
dose of DSP-7888 Dosing Emulsion are based on the number of patients with DLTs out of the 
total number of DLT-eligible patients in a given cohort. The criteria are as specified below: 
• If 0 or 1 of 6 patients at the starting dose level experience a DLT, the dose level is 
eligible for consideration as the recommended dose of DSP-7888 Dosing Emulsion 
• If 2 or more of 6 patients at a given dose level experience a DLT, the dose will be 
decreased. Further enrollment will be at the lower dose level. If 0 or 1 of 6 patients at 


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the lower dose level experience a DLT, the dose level is eligible for consideration as 
the recommended dose of DSP-7888 Dosing Emulsion 
The determination of the recommended dose of DSP-7888 Dosing Emulsion in a given study 
arm also will be based on overall tolerability, including a review of persistent Grade 2 AEs and a 
review of AEs occurring beyond the first 2 cycles.   
The safety and tolerability of DSP-7888 Dosing Emulsion in combination with immunotherapy 
PD-1 inhibitors will be assessed for the duration of study treatment and 30 days follow-up. 
6.6. 
Safety Review Committee 
The Safety Review Committee (SRC) for Phase 1b dose-escalation will be chaired by the 
 
. The SRC will include the 
Principal Investigator (or delegate) from each of the investigational sites. The SRC will also 
include a representative from 
 PV (or designee), an 
 Biostatistician 
(or designee), and a representative from 
 Clinical Research. The SRC will review 
the safety and tolerability of DSP-7888 Dosing Emulsion in combination with nivolumab and 
pembrolizumab in each cohort to decide the next dose level to be tested. In addition, all immune-
related AEs occurring in Arm 1 and Arm 2 will be evaluated throughout the conduct of this 
study. The SRC’s review and assessment will include all available safety data from each cohort, 
together with available PD data. The SRC’s review will also include an assessment of all cases, 
individually and in aggregate, for those patients who meet the criteria for DLT in order to 
determine the clinical significance and basis for their inclusion or exclusion in the decision for 
dose change. 
The SRC will review and agree on the recommended maximum tolerated dose prior to enrolling 
patients in the dose-expansion part. In the dose-search cohort (Phase 1b), the stopping rule will 
follow the rule of the 3+3 design. All decisions made by the SRC will be documented and 
provided in writing to the investigators before dosing any new patients. 
In Phase 2 of the study, the Sponsor will decide the necessity for a study suspension, protocol 
amendment, continuation of enrollment, or termination of the study if the following criteria are 
met: 
• Any cases of death (other than death related to progressive disease) that occur from 
the start of treatment with DSP-7888 Dosing Emulsion and up to 30 days from the 
last DSP-7888 Dosing Emulsion administration, and deemed by the Sponsor to be 
related to any of the study’s drugs 
• If the percentage of patients in this study presenting with drug‑related (assessed by 
Sponsor) Grade 4 or higher AE within a particular medical concept (eg, 
hypersensitivity) is higher than that reported in patients treated with DSP-7888 
Dosing Emulsion within the clinical program, and as reported in the literature 
6.7. 
Procedures 
The safety and tolerability of DSP-7888 Dosing Emulsion in combination with immunotherapy 
PD-1 inhibitors will be assessed for the duration of study treatment and follow-up. Refer to Table 
7,Table 8, and Table 9 for the respective schedules of assessments. Adherence to the study 


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design requirements, including those specified in the Schedule of Assessments is essential and 
required for study conduct. 


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Table 7: 
Schedule of Assessments (Arm 1, Combination of DSP-7888 Dosing Emulsion and Nivolumab [14-Day Study 
Cycles]) 
Tests and Procedures 
Pre-
Screening 
Pre-Study 
Evaluation 
On-Study Evaluationsa 
End of 
Treatment 
Follow-Up 
For OS 
Cycle 1 
Cycle 2 
Cycle 
3 
Cycle 
4 
Cycle 
5 
Cycle 
6 
Cycle 
7+ 
Week 
 
 
0 
1 
2 
3 
4 
6 
8 
10 
12+ 
30 days after 
last 
DSP-7888 
Dosing 
Emulsion 
dose 
Every 3 
months after 
date off 
treatment 
Day 
Any time 
before 
enrollment 
Within 28 days 
prior to first dose 
of study drug 
1 
8 
15 
22 
29 
43 
57 
71 
85+ 
Window 
 
28 days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
+7 daysb 
 
Pre-screening consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HLA-typing (A/B locus and DRB1 
locus) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion review 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical and cancer history 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
 
X 
X 
 
Xc 
 
Xc 
Xc 
Xc 
Xc 
Xc 
X 
 
Serum pregnancy test, if applicable 
 
X 
 
 
 
 
 
 
 
 
 
 
 
ECOG performance status 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Complete vital signs 
 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Body weight 
 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Hematology 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Clinical chemistry 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Thyroid function test 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Urinalysis 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Pulse oximetry 
 
X 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
 
Blood samples for Hepatitis B/C & 
HIV 
 
X 
 
 
 
 
 
 
 
 
 
 
 
ECHO/MUGA 
 
X 
 
 
X 
 
 
X 
 
 
Xd 
X 
 
12-lead electrocardiogram 
 
X 
Xe 
 
Xe 
 
 
X 
 
 
Xf 
X 
 
Tumor tissue samples for 
biomarkersg 
 
Xh 
 
 
 
 
 
 
 
 
Xi 
 
 
Tumor tissue samples for future 
biomarker analysisj 
 
X 
 
 
 
 
 
 
 
 
Xi 
 
 


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Tests and Procedures 
Pre-
Screening 
Pre-Study 
Evaluation 
On-Study Evaluationsa 
End of 
Treatment 
Follow-Up 
For OS 
Cycle 1 
Cycle 2 
Cycle 
3 
Cycle 
4 
Cycle 
5 
Cycle 
6 
Cycle 
7+ 
Week 
 
 
0 
1 
2 
3 
4 
6 
8 
10 
12+ 
30 days after 
last 
DSP-7888 
Dosing 
Emulsion 
dose 
Every 3 
months after 
date off 
treatment 
Day 
Any time 
before 
enrollment 
Within 28 days 
prior to first dose 
of study drug 
1 
8 
15 
22 
29 
43 
57 
71 
85+ 
Window 
 
28 days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
±2 
days 
+7 daysb 
 
Blood samples for CTL inductionk 
 
Xl 
 
 
Xm 
 
Xm 
 
Xm 
 
Xm,n 
X 
 
Blood samples for future 
biomarker analysiso 
 
Xl 
 
 
Xm 
 
Xm 
 
Xm 
 
Xm,n 
X 
 
Concomitant medications 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse eventsp 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Administer DSP-7888 Dosing 
Emulsion 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Administer nivolumab 
 
 
 
 
 
 
X 
X 
X 
X 
X 
 
 
Follow-up for overall survival 
 
 
 
 
 
 
 
 
 
 
 
 
Xq 
Objective disease assessmentr 
 
X 
First post-treatment assessment at Week 4 (Cycle 3), followed by one at Week 12 (Cycle 7), then 2 
subsequent assessments every 6 weeks at Week 18, Week 24 (Cycle 10, Cycle 13), and finally every 12 
weeks (Cycle 19 and every 6 cycles) until disease progression.s 
Abbreviations: AE = adverse event; CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; CTL = cytotoxic T lymphocyte; ECG = 
echocardiogram; ECOG = Eastern Cooperative Oncology Group; ECHO = echocardiogram; FFPE =  formalin-fixed and paraffin embedded; HIV = human 
immunodeficiency virus; HLA = human leukocyte antigen; ICF = informed consent form; iRECIST = immune Response Evaluation Criteria in Solid Tumors MRI = 
magnetic resonance imaging; MUGA = multiple gated acquisition; OS = overall survival; PD-L1 = programmed death ligand 1; PET = positron emission tomography; 
PBMC = peripheral blood mononuclear cells; RECIST = Response Evaluation Criteria in Solid Tumors; TIL = tumor-infiltrating lymphocytes; TIS = tumor immune 
signature; WT1 = Wilms Tumor 1 
a All tests must be performed PRIOR to injection of study treatment, with the exception of ECG. 
b Complete End of Treatment assessment procedures before patient receives new anti-cancer treatment. 
c Inspection of prior injection sites will be done at each administration of the vaccine.  
d . From Cycle 4, ECHO/MUGA tests for ejection fraction will be done on Day 1 every 6th cycle (eg, Cycle 10, 16, 22). 
e Obtained at least 2 hours post-dose of DSP-7888 Dosing Emulsion. 
f 
From Cycle 4, 12-lead electrocardiograms will be performed on Day 1 of every 3rd Cycle (eg, Cycle 7, 10, 13). 
g It should be ensured that a total of at least 23 slides of archival samples and/or the equivalent amount of archival tissue block and/or fresh biopsy samples from the 
enrolled patients are available. These samples must contain sufficient tumor tissue. 


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h Collection of tumor tissue samples at Pre-Study evaluation is mandatory. Either archival tissue or fresh biopsy samples at Pre-study evaluation would be acceptable. 
Collection of fresh biopsy samples is required, if medically feasible. 
i 
Sample to taken at week 12 (Cycle 7), see Section 10.1 for the timepoints and circumstances for tumor tissue sample collection for post treatment evaluations after 
Week 12 (Cycle 7). Tumor tissue samples will be collected at End of Treatment only if patient discontinues from study prior to Week 12. 
j 
Either archival tissue or fresh biopsy samples will be collected only after the patient signs an additional separate informed consent for these optional samples. A total 
of 6 to 8 slides will be sent to the central laboratory for analyses. 
l 
If blood is not collected at Screening, it may be obtained on Day 1 prior to administration of protocol therapy. 
m Samples to be taken pre-dosing with DSP-7888 Dosing Emulsion. 
n Sample to be taken every 2 cycles pre-dosing until dosing is discontinued (eg, Cycle 7, 9, 11, 13). 
o Additional informed consent is needed prior to collection at Pre-Study evaluation. Serum, PBMC and ctDNA (plasma) are included as a blood sample.  PBMC will be 
prepared from whole blood at the Central Laboratory. The whole blood sample for PBMC preparation should be shipped from the clinical site to the central laboratory on 
the sample collection date. Blood samples for ctDNA (plasma) is collected at Screening only.  
p Use CTCAE v4.03 term, if appropriate (Note: the verbatim term should be reported, not the associated CTCAE term). All AEs must be reported for each patient from 
the date of ICF signature until 30 days after the last dose of study drug administration. 
q Follow-up until end of life or end of the study, whichever occur first. Follow up to occur every 3 months and/or on an ad-hoc basis for safety or regulatory purposes, 
or a prespecified analysis 
r 
Assessment consists of chest/abdomen/pelvis CT/MRI. A bone scan and MRI of the brain will be conducted when clinically indicated. Imaging technology should be 
consistent across the study, CT component of PET/CT assessments are sufficient to be used if PET/CT scan was done at baseline. 
s 
Images are assessed according to RECIST v1.1 and iRECIST. 
 
 
 


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Table 8: 
Schedule of Assessment (Arm 2 of Phase 1b, Combination of DSP-7888 Dosing Emulsion and Pembrolizumab 
[21-Day Study Cycles]) 
Tests and Procedures 
Pre-
Screening 
Pre-Study 
Evaluation 
On-Study Evaluations1 
End of 
Treatment 
Follow-Up 
For OS 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Cycle 5+ 
Week 
 
 
0 
1 
2 
3 
4 
5 
6 
9 
12 
30 days after 
last DSP-
7888 Dosing 
Emulsion 
dose 
Every 3 
months after 
date off 
treatment 
Day 
Any time 
before 
enrolment 
Within 28 
days prior 
to first dose 
of study 
drug 
1 
8 
15 
22 
29 
36 
43 
64 
85 
Window 
 
28 days 
±2 days 
±2 days 
±2 days 
±2 days 
±2 days 
+7 days18 
 
Pre-screening consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HLA-typing (A/B locus and 
DRB1 locus) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion review 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical, cancer history 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
 
X 
X 
 
 
X2 
 
 
X2 
X2 
X2 
X 
 
Serum pregnancy test, if 
applicable 
 
X 
 
 
 
 
 
 
 
 
 
 
 
ECOG performance status 
 
X 
 
 
 
X 
 
 
X 
X 
X 
X 
 
Complete vital signs 
 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
Body Weight 
 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
Hematology 
 
X 
 
X 
X 
X 
 
 
X 
X 
X 
X 
 
Clinical chemistry 
 
X 
 
X 
X 
X 
 
 
X 
X 
X 
X 
 
Thyroid function test 
 
X 
 
 
 
X 
 
 
X 
X 
X 
X 
 
Urinalysis 
 
X 
 
X 
X 
X 
 
 
X 
X 
X 
X 
 
Pulse oximetry 
 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
Blood samples for Hepatitis B/C 
& HIV 
 
X 
 
 
 
 
 
 
 
 
 
 
 
ECHO/MUGA 
 
X 
 
 
 
X 
 
 
X 
 
X3 
X 
 
12-lead electrocardiogram 
 
X 
X4 
 
 
X4 
 
 
X 
 
X5 
X 
 
Tumor tissue samples for 
biomarkers 
 
X6 
 
 
 
 
 
 
 
 
X7 
 
 
Tumor tissue samples for future 
biomarker analysis8 
 
X 
 
 
 
 
 
 
 
 
X7 
 
 
Blood samples for CTL 
induction9 
 
X10 
 
 
 
X11 
 
 
X11 
 
X11,12 
X 
 
Blood samples for future 
biomarker analysis13 
 
X10 
 
 
 
X11 
 
 
X11 
 
X11,12 
X 
 
Concomitant medications 
 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 


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Tests and Procedures 
Pre-
Screening 
Pre-Study 
Evaluation 
On-Study Evaluations1 
End of 
Treatment 
Follow-Up 
For OS 
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
Cycle 5+ 
Week 
 
 
0 
1 
2 
3 
4 
5 
6 
9 
12 
30 days after 
last DSP-
7888 Dosing 
Emulsion 
dose 
Every 3 
months after 
date off 
treatment 
Day 
Any time 
before 
enrolment 
Within 28 
days prior 
to first dose 
of study 
drug 
1 
8 
15 
22 
29 
36 
43 
64 
85 
Window 
 
28 days 
±2 days 
±2 days 
±2 days 
±2 days 
±2 days 
+7 days18 
 
Adverse events14 
 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
Administer DSP-7888 Dosing 
Emulsion 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
 
 
Administer pembrolizumab 
 
 
 
 
 
X 
 
 
X 
X 
X 
 
 
Follow-up for overall survival 
 
 
 
 
 
 
 
 
 
 
 
 
X15 
Objective disease assessment16 
 
X 
First post-treatment assessment at Week 6 (Cycle 3), then 3 subsequent assessments at Week 12, Week 18, Week 24 
(Cycle 5, Cycle 7, Cycle 9), and finally every 12 weeks (Cycle 13 and every 4 cycle) until disease progression.17 
AE = adverse event; CT = computed tomography; CTCAE = Common Terminology Criteria for Adverse Events; CTL = cytotoxic T lymphocyte; ECG = echocardiogram; 
ECOG = Eastern Cooperative Oncology Group; ECHO = echocardiogram; HIV = human immunodeficiency virus; HLA = human leukocyte antigen; ICF = informed consent 
form; IHC = immunohistochemistry; iRECIST = immune Response Evaluation Criteria in Solid Tumors; MRI = magnetic resonance imaging; MUGA = multiple gated 
acquisition; OS = overall survival; PD-L1 = programmed death ligand 1; PET = positron emission tomography; PMBC = peripheral blood mononuclear cells; RECIST = 
Response Evaluation Criteria in Solid Tumors; TIL = tumor infiltrating lymphocytes; TIS = tumor immune signature; TMB = tumor mutational burden; WT1 = Wilms Tumor 1 
1. All tests must be performed PRIOR to injection of study treatment, with the exception of ECG. 
2. Inspection of prior injection sites will be done at each administration of the vaccine. 
3. From Cycle 3, ECHO/MUGA tests for ejection fraction will be done on Day 1 of every 4th cycle (eg, Cycle 7, 11, 15). 
4. Obtained at least 2 hours post-dose of DSP-7888 Dosing Emulsion. 
5. From Cycle 3, 12-lead electrocardiograms will be performed on Day 1 of every 2nd Cycle (eg, Cycle 5, 7, 9). 
6. Collection of tumor tissue samples at pre-study evaluation is mandatory.  Either archival tissue or fresh biopsy samples at Pre-study evaluation would be acceptable.  
7.Sample to be taken at Week 12 (Cycle 5), see Section 10.1 for the timepoints and circumstances for tumor tissue sample collection for post-treatment evaluations after Week 12 
(Cycle 5). Tumor tissue samples will be collected at End of Treatment only if patient discontinues from study prior to Week 12. Additional informed consent is needed prior to 
collection. 
8. Either archival tissue or fresh biopsy samples will be collected only after the patient signs an additional informed consent for these optional samples.  A total of 6 to 8 slides will 
be sent to the central laboratory for analyses. 
9. PBMCs will be prepared from whole blood at the Central Laboratory.  The whole blood sample for PBMC preparation should be shipped from the clinical site to the Central 
Laboratory on the sample collection date. 
10. If blood is not collected at Screening, it may be obtained on Day 1 prior to administration of protocol therapy. 
11. Samples to be taken pre-dosing with DSP-7888 Dosing Emulsion. 
12. Sample to be taken every 2 cycles, pre-dosing until dosing is discontinued (eg, Cycle 5, 7, 9, 11, 13). 
13. Additional informed consent is needed prior to collection at Pre-Study evaluation.  Serum, PBMC and ctDNA (plasma) are included as a blood sample.  PBMC will be 
prepared from whole blood at Central Laboratory.  The whole blood sample for PBMC preparation should be shipped from clinical site to central laboratory on the sample 
collection date.  Blood sample for ctDNA (plasma) is collected at Screening only. 
14.Use CTCAE v4.03 term, if appropriate (Note: the verbatim term should be reported, not the associated CTCAE term. All AEs must be reported for each patient from the date of 
ICF signature until 30 days after the last dose of study drug administration. 


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15. Follow-up until end of life or end of the study, whichever occur first. Follow up to occur every 3 months and/or on an ad-hoc basis for safety or regulatory purposes, or a 
prespecified analysis 
16. Assessment consists of chest/abdomen/pelvis CT/MRI.  A bone scan and MRI of the brain will be conducted when clinically indicated. Imaging technology should be 
consistent across the study, CT component of PET/CT assessments are sufficient to be used if PET/CT scan was done at baseline. 
17. Images are assessed according to RECIST v1.1 and iRECIST. 
18. Complete End of Treatment assessment procedures before patient receives new anti-cancer treatment. 
 


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Table 9: 
Schedule of Assessments (Phase 2, Combination of DSP-7888 Dosing Emulsion and Pembrolizumab for Ovarian 
Cancer) 
Period 
Pre-
screening  
Screening 
period 
Treatment Period 
(All procedure must be performed PRIOR to injection of study 
treatment) 
Follow-up 
Period 
Notes 
Treatment Cycle 
1 
2 
3 
4 
5+* 
EOT 
(30 day 
after 
last 
dose) 
Disease 
follow 
up** 
Survival 
Follow up 
*Cycle 5 and subsequent cycles up to Cycle 
35 
**Applicable for only if patients who 
discontinue study treatment for a reason 
other than disease progression 
Day   
1 
8 
15 
1 
8 
15 
1 
1 
1 
Week (from 1st dose) 
0 
1 
2 
3 
4 
5 
6 
9 
12 
Scheduling Window 
(Days) 
- 
-28 to 1* 
0 
±2 
±2 
±2 
±2 
±2 
±3 
±3 
±7 
+7a 
±7 
±14 
*Procedures in screening should be 
completed within 28 days from Cycle 1 
Day1 
Study Drug Administration 
DSP-7888 Dosing 
Emulsion 
 
 
X 
X 
X 
X 
 
 
X 
X 
X 
 
 
 
 
Pembrolizumab 
 
 
 
 
 
X 
 
 
X 
X 
X 
 
 
 
 
Administrative procedure 
HLA screening 
informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed Consent* 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
*Main informed consent and informed 
consent for future biomarker (optional) for 
willing participants 
Inclusion and 
Exclusion criteria 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography and 
Medical History 
 
X* 
 
 
 
 
 
 
 
 
 
 
 
 
*including COVID-19 history and 
vaccination history  
Prior and 
Concomitant 
Medications 
 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
Cancer history and 
Cancer Prior 
Treatment 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 


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Period 
Pre-
screening  
Screening 
period 
Treatment Period 
(All procedure must be performed PRIOR to injection of study 
treatment) 
Follow-up 
Period 
Notes 
Treatment Cycle 
1 
2 
3 
4 
5+* 
EOT 
(30 day 
after 
last 
dose) 
Disease 
follow 
up** 
Survival 
Follow up 
*Cycle 5 and subsequent cycles up to Cycle 
35 
**Applicable for only if patients who 
discontinue study treatment for a reason 
other than disease progression 
Day   
1 
8 
15 
1 
8 
15 
1 
1 
1 
Week (from 1st dose) 
0 
1 
2 
3 
4 
5 
6 
9 
12 
Scheduling Window 
(Days) 
- 
-28 to 1* 
0 
±2 
±2 
±2 
±2 
±2 
±3 
±3 
±7 
+7a 
±7 
±14 
*Procedures in screening should be 
completed within 28 days from Cycle 1 
Day1 
New anticancer 
therapy 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
*Every 12 weeks up to 105 weeks and/or on 
an ad-hoc basis for safety or regulatory 
purposes, or a prespecified analysis. 
Safety assessment 
Physical 
Examination* 
 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
 
*Inspection of prior injection site will be 
done 
Vital Sign and 
Weight 
 
X* 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
*Height will be measured only at screening 
12-lead ECG 
 
X 
 
 
 
 
 
 
X 
 
 
X 
 
 
 
ECHO/MUGA 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECOG performance 
status 
 
X 
X 
X 
X 
X 
 
 
X 
X 
X 
X 
 
 
 
Adverse Events 
X* 
X** 
X 
X 
X 
X 
 
 
X 
X 
X 
X** 
 
 
* SAE related to study procedure will be 
reported to 
 Safety 
**AE must be collected from the date of 
main ICF to 30 days after last dose 


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Period 
Pre-
screening  
Screening 
period 
Treatment Period 
(All procedure must be performed PRIOR to injection of study 
treatment) 
Follow-up 
Period 
Notes 
Treatment Cycle 
1 
2 
3 
4 
5+* 
EOT 
(30 day 
after 
last 
dose) 
Disease 
follow 
up** 
Survival 
Follow up 
*Cycle 5 and subsequent cycles up to Cycle 
35 
**Applicable for only if patients who 
discontinue study treatment for a reason 
other than disease progression 
Day   
1 
8 
15 
1 
8 
15 
1 
1 
1 
Week (from 1st dose) 
0 
1 
2 
3 
4 
5 
6 
9 
12 
Scheduling Window 
(Days) 
- 
-28 to 1* 
0 
±2 
±2 
±2 
±2 
±2 
±3 
±3 
±7 
+7a 
±7 
±14 
*Procedures in screening should be 
completed within 28 days from Cycle 1 
Day1 
Efficacy assessment 
Tumor 
imaging/response 
assessment* 
 
X 
 
 
 
 
 
 
X 
 
X** 
X*** 
X**** 
 
*Assessed by RECIST 1.1 and followed by 
iRECIST after progressive disease per 
RECIST 1.1. 
**Cycle 5, 7, 9 and subsequent assessments 
every 4 Cycle (Cycle 13, 17, 21 etc.) 
***Not mandated if last assessment 
performed less than 28 days from EOT 
****Every 12 weeks from last assessment 
CA-125 sample 
collection/response 
assessment 
 
X 
X 
 
 
X 
 
 
X 
X 
X* 
X 
X** 
 
* Every 2 Cycle (eg, Cycle 5,7,9) 
**Every 12 weeks from last assessment  
Survival status 
 
 
 
 
 
 
 
 
 
 
 
 
 
X* 
*Every 12 weeks up to 105 weeks and/or on 
an ad-hoc basis for safety or regulatory 
purposes, or a prespecified analysis. 
Clinical laboratory assessment 
HLA-typing* 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Performed by Central Lab (A and B locus 
and DRB1 locus). One tube for HLA 
typing, and the second tube stored for 
exploratory endpoints.  
Pregnancy Test 
 
X* 
 
 
 
 
 
 
 
 
 
 
 
 
*if applicable. Either serum or urine 
HBV, HCV and HIV 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology 
 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
 
 
Serum Chemistry 
 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
 
 


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Period 
Pre-
screening  
Screening 
period 
Treatment Period 
(All procedure must be performed PRIOR to injection of study 
treatment) 
Follow-up 
Period 
Notes 
Treatment Cycle 
1 
2 
3 
4 
5+* 
EOT 
(30 day 
after 
last 
dose) 
Disease 
follow 
up** 
Survival 
Follow up 
*Cycle 5 and subsequent cycles up to Cycle 
35 
**Applicable for only if patients who 
discontinue study treatment for a reason 
other than disease progression 
Day   
1 
8 
15 
1 
8 
15 
1 
1 
1 
Week (from 1st dose) 
0 
1 
2 
3 
4 
5 
6 
9 
12 
Scheduling Window 
(Days) 
- 
-28 to 1* 
0 
±2 
±2 
±2 
±2 
±2 
±3 
±3 
±7 
+7a 
±7 
±14 
*Procedures in screening should be 
completed within 28 days from Cycle 1 
Day1 
Urinalysis 
 
X 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
 
 
Coagulation 
Parameters 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
T3, FT4 and TSH 
 
X 
 
 
 
X 
 
 
X 
 
X* 
X 
 
 
* Every 2 Cycle (eg, Cycle 5,7,9) 
Biomarker sample collection 
Blood samples for 
CTL induction* 
 
X 
 
 
 
X 
 
 
X 
 
X** 
X 
 
 
*Samples to be taken at screening and, 
during treatment, prior to each dose**Cycle 
5, 7, 9 and subsequent assessments every 4 
Cycle (Cycle 13, 17, 21 etc.) 
Blood samples for 
future biomarker 
(optional) * 
 
X 
 
 
 
X 
 
 
X 
 
X** 
X 
 
 
*Only patients who provides informed 
consent for future biomarker samples to be 
taken prior to dosing. 
Serum, PBMC and ctDNA (plasma) are 
included as a blood sample. PBMC will be 
prepared from whole blood at Central 
Laboratory. The whole blood sample for 
PBMC preparation should be shipped from 
clinical site to central laboratory on the 
sample collection date. 
**Cycle 5, 7, 9 and subsequent assessments 
every 4 cycles (Cycle 13, 17, 21 etc.) 
ctDNA only at screening, Cycle 3 Day1, 
Cycle 5 Day1, next visit when patients have 
PR or CR with RECIST criteria, and EOT. 


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Period 
Pre-
screening  
Screening 
period 
Treatment Period 
(All procedure must be performed PRIOR to injection of study 
treatment) 
Follow-up 
Period 
Notes 
Treatment Cycle 
1 
2 
3 
4 
5+* 
EOT 
(30 day 
after 
last 
dose) 
Disease 
follow 
up** 
Survival 
Follow up 
*Cycle 5 and subsequent cycles up to Cycle 
35 
**Applicable for only if patients who 
discontinue study treatment for a reason 
other than disease progression 
Day   
1 
8 
15 
1 
8 
15 
1 
1 
1 
Week (from 1st dose) 
0 
1 
2 
3 
4 
5 
6 
9 
12 
Scheduling Window 
(Days) 
- 
-28 to 1* 
0 
±2 
±2 
±2 
±2 
±2 
±3 
±3 
±7 
+7a 
±7 
±14 
*Procedures in screening should be 
completed within 28 days from Cycle 1 
Day1 
Tumor tissue 
collection 
 
X* 
 
 
 
 
 
 
 
 
X** 
X** 
 
 
* Fresh biopsy (if medically feasible), 
archival tumor block, or newly cut slides 
are required at screening. 
**Cycle 5, or EOT if earlier, if medically 
feasible  
Tumor samples for 
future biomarker 
(optional)  
 
X* 
 
 
 
 
 
 
 
 
X** 
X** 
 
 
*Only patients who provides informed 
consent for future biomarker. Either 
archival tissue or fresh biopsy samples will 
be collected and a total of 6 to 8 slides will 
be sent to the central laboratory for analyses 
**Cycle 5, or EOT if earlier, if medically 
feasible  
a Complete End of Treatment assessment procedures before patient receives new anti-cancer treatment. 


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7. 
SELECTION AND WITHDRAWAL OF PATIENTS 
7.1. 
Inclusion Criteria 
Patients must fulfill each of the following requirements: 
Phase 1b 
Phase 1b Dose Search Part 
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: 
a. Patients must not be considered eligible for a potentially curative resection 
b. 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 


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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 (see Appendix 3)  
Both Phase 1b Dose Search Part and Phase 1b Enrichment Cohort: 
2. Patients must be positive for at least 1 of the following human leukocyte antigens 
(HLAs): 
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. ≥ 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 drug  
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 of study drug 
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 ULN or <5 × ULN if considered to be due to 
liver metastases 
11. Estimated glomerular filtration rate (GFR) >40 mL/min using the Cockcroft-Gault 
equation 
12. Multigated acquisition (MUGA) scan or echocardiogram (ECHO) with left ventricular 
ejection fraction (LVEF) >40% 
13. Life expectancy ≥3 months 
14. Patients must be willing to provide a signed and dated ICF 
Phase 2 
Patients eligible for inclusion in this study must meet all of the following criteria: 


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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 standard of care 
2. Patients must be positive for at least 1 of the following HLAs as assessed by central 
laboratory: 
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 the 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  
a. Maintenance is not considered a separate line of treatment (even if patients who are 
BRCA mutation-positive received a PARP inhibitor following induction therapy with 
a platinum doublet, eg, bevacizumab)  
b. Neoadjuvant and adjuvant systemic therapy will be counted as one line of therapy 
c. 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 (v.1.1) 
7. Patients must have an ECOG performance status of 0 or 1 
8. Patients must have adequate organ function, defined as follows: 
System 
Laboratory Value 
Hematologic  
Absolute neutrophil count (ANC) 
≥1,500 / μL (without granulocyte colony 
stimulating factor (G-CSF)) 
Platelets 
≥100,000 / μL (without transfusion) 
Hemoglobin 
≥9.0 g/dL (without transfusion) 
Renal 
Serum creatinine OR estimated GFR 
using the Cockcroft-Gault equation 
≤1.5 × ULN OR ≥40 mL/min using the 
Cockcroft-Gault equation for patients with 
creatinine levels >1.5 × ULN 
Hepatic 
Serum total bilirubin 
≤1.5 × ULN 


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AST and ALT 
≤2.5 × ULN OR ≤5 × ULN for patients with 
liver metastases 
Cardiac 
MUGA or ECHO with LVEF 
≥40% 
QTcF (QT corrected based on 
Fridericia’s equation) interval  
<480 msec 
Coagulation 
International Normalized Ratio 
(INR) or Prothrombin Time (PT) 
≤1.5 × ULN, unless the patient is receiving 
anticoagulant therapy and the PT is within 
therapeutic range  
Activated Partial Thromboplastin 
Time (aPTT) or Partial 
Thromboplastin Time (PTT) 
≤1.5 × ULN, unless the patient is receiving 
anticoagulant therapy and the aPTT is within 
therapeutic range 
9. Patients must provide either 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 to 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 for >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 (for females and males alike) after the last dose of study drug 
12. Life expectancy ≥3 months 
13. Patients who had stayed on the last treatment for at least 12 weeks without any evidence 
of progression 
7.2. 
Exclusion Criteria 
Phase 1b  
Phase 1b Dose Search and Phase 1b Enrichment Part: 
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) 
within Phase 1b dose search part.  
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 


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radiographic image documentation of stability. Patients must have no clinical symptoms 
from brain metastases and not have required systemic corticosteroids (equivalent to 
>10 mg/day prednisone; see Appendix 5) 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 (see Appendix 5) 
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, noninfectious pneumonitis 
9. Known hypersensitivity to a component of protocol therapy: 
a. Patients with known hypersensitivity to any of the components of DSP-7888 Dosing 
Emulsion 
b. 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 nonmelanoma 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 QT corrected interval, based on Fridericia’s equation (QTcF), 
>480 msec (Common Terminology Criteria for Adverse Events [CTCAE] = Grade 2) or 
other factors that increase the risk of QT prolongation or arrhythmic events (eg, 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 


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15. Known history of human immunodeficiency virus (HIV) infection, active hepatitis B, or 
untreated active 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 (HBsAg) 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 
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 
(equivalent to >10 mg/day prednisone; see Appendix 5) 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 immunoregulatory receptors or 
mechanisms (examples of such drugs include, but are not limited to, antibodies against, 
eg, 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 timeframe 
prior to the first dose of the study drug 
a. Cytotoxic chemotherapy, hormonal therapy; ≤3 weeks 
b. Targeted therapy except for monoclonal antibody; ≤3 weeks 
c. Immune therapy, biologic therapy (eg, antibodies); ≤4 weeks 
d. Other investigational agents: ≤4 weeks 
e. Radiation therapy (except for localized radiotherapy for analgesic purpose) ≤4 weeks 
f. Radiation therapy (localized radiotherapy for analgesic purpose) ≤1 week 
g. 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:  
a. curatively treated basal cell or squamous cell carcinoma of skin 
b. curatively treated superficial bladder cancer, carcinoma in situ of the cervix,  


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c. 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 
exceptions 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 (equivalent to >10 mg/day 
prednisone; see Appendix 5) 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 active hepatitis C: 
• In cases of negative results for HBsAg with positive Hepatitis B 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 (NYHA) Class III or IV cardiac disease, including 
preexisting clinically significant ventricular arrhythmia, 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 
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. Patient who are pregnant or breastfeeding 
18. Patients who have a 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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7.3. 
Withdrawal Criteria 
7.3.1. 
Reasons for Discontinuation of Protocol Therapy 
Patients have the right to withdraw fully or partially from the study at any time and for any 
reason without prejudice to their future medical care by the physician or at the institution. 
Withdrawal of partial consent means that the patient does not wish to take investigational 
product any longer but is still willing to collaborate in providing further data by continuing on 
the study (eg, participate in all subsequent study visits or procedures). Patients may decline to 
continue receiving investigational product at any time during the study. These patients, as well as 
those who have stopped receiving investigational product for other reasons (eg, investigator or 
Sponsor concern) should continue the schedule of study observations. The patients may 
withdraw consent for continued treatment and still provide consent to be followed up in the 
follow-up period. 
Patients will be discontinued from protocol therapy for any of the following reasons: 
• Patients completes 35 cycles (approximately 105 weeks) of study treatment (Phase 2 
part only) 
Note: if the patient is experiencing clinical benefit, and if, in the opinion of the 
investigator, it is in the patient’s best interest to continue the study beyond 35 cycles, 
the patient may continue treatment, after documented discussion with the Sponsor 
• Documented disease progression (see Appendix 2)  
• The need for a prohibited treatment for a concomitant illness or AE 
• An AE that precludes further administration of DSP-7888 Dosing Emulsion (see 
Section 8.3.1 and Section 8.3.2) 
• Patient withdraws consent for continued administration of DSP-7888 Dosing 
Emulsion, nivolumab, or pembrolizumab  
Note: if a patient withdrawals consent from study treatment, the patient may maintain 
his/her consent to participate in the follow-up portion of the study 
• The investigator believes it is in the patient’s best interest to discontinue protocol 
treatment or to initiate alternative treatment 
• Pregnancy 
• Lost to follow-up (3 attempts to contact the patient must be made by the investigative 
site by phone or email before a patient is considered lost to follow-up) 
• Patient moves out of the investigator’s catchment area or is unable to continue to 
come to the investigational site 
• At Sponsor’s request 
7.3.2. 
Reasons for Discontinuation from the Clinical Study 
Reasons for discontinuation from the study include: 


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• Patient withdraws consent for continued participation 
• Lost to follow-up 
• Death of the patient 
• The Sponsor deems it necessary to discontinue the study 
Withdrawal of full consent for a study means that the patient does not wish to receive further 
investigational treatment and does not wish to or is unable to continue further study participation. 
Any patient may withdraw full consent to participate in the study at any time during the study. 
The investigator will discuss with the patient the most appropriate way to withdraw to ensure the 
patient’s health. 
No patients will be replaced during the dose-expansion part of the clinical study. Patients are free 
to withdraw from the study at any time without providing reason(s) for withdrawal and without 
prejudice to further treatment.   
Patients withdrawing from the study will be requested to complete the same final evaluations as 
patients completing the study according to this protocol, particularly safety evaluations. The aim 
is to record data in the same way as for patients who complete the study. 
Reasonable efforts will be made to contact patients who are lost to follow-up. These efforts must 
be documented in the patient’s file.  
The Sponsor has the right to terminate the study at any time. In this event, the investigator(s) will 
be informed of the reason for study termination. 


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8. 
TREATMENT OF PATIENTS 
8.1. 
Description of Study Drugs 
8.1.1. 
DSP-7888 Dosing Emulsion Investigational Product  
DSP-7888 Dosing Emulsion, also known as Adegramotide/Nelatimotide (INN) and 
Ombipepimut-S (USAN), is a synthetic peptide vaccine that consists of 2 synthetic peptide 
constructs: Nelatimotide (INN) (DSP-7888-K [killer peptide; an MHC Class I peptide]) and 
Adegramotide (INN) (DSP-7888-H [helper peptide; an MHC Class II peptide]). Both constructs 
are derived from the WT1 protein. DSP-7888 Dosing Emulsion, consisting of DSP-7888 in 
suspension with montanide 51 VG (labeled as DSP-7888-M), will be administered at the study 
site by staff trained in the administration of intradermal drugs.   
8.1.2. 
Nivolumab 
Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells inhibits 
T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some 
tumors and signaling through this pathway can contribute to inhibition of active T-cell immune 
surveillance of tumors. Nivolumab is a human immunoglobulin G4 monoclonal antibody that 
binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 
pathway-mediated inhibition of the immune response, including the antitumor immune response. 
Nivolumab will be administered at 240 mg every 2 weeks, as per the approved label.  
On the days when both DSP-7888 Dosing Emulsion and nivolumab are administered, DSP-7888 
Dosing Emulsion should be administered first. Nivolumab will be obtained by the clinical site. 
8.1.3. 
Pembrolizumab 
Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks interaction 
with its ligands, PD-L1 and PD-L2. This binding results in the activation of T-cell–mediated 
immune responses against tumor cells. Blocking PD-1 activity has resulted in decreased tumor 
growth in genetically identical mouse tumor models. Pembrolizumab will be administered at a 
dose of 200 mg/8 mL IV over 30 (±5) minutes every 21 days (3 weeks). On the days when both 
DSP-7888 Dosing Emulsion and pembrolizumab are administered, DSP-7888 Dosing Emulsion 
should be administered first. Pembrolizumab may be obtained by the clinical site in Phase 1b of 
the study. For Phase 2 of the study, pembrolizumab will be provided by 
 
8.2. 
Treatment Dose and Schedule (Phase 1 and Phase 2) 
Treatment dosing and treatment schedules for DSP-7888 Dosing Emulsion, nivolumab, and 
pembrolizumab are provided in Table 10.   


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Table 10: 
DSP-7888 Dosing Emulsion, Nivolumab, and Pembrolizumab Treatment Dose and Schedule 
DSP-7888 Dosing Emulsion 
Treatment Schedule 
DSP-7888 Dosing Emulsion, Nivolumab, Pembrolizumab 
Dose Level 
Dose 
Intensity 
Number of 
Injection* 
Sites 
Amount Per 
Injection* Site 
(mL) 
Total Amount to 
Administer Per 
Dosing Day (mL) 
Nivolumab Arm  
(Arm 1) 
Pembrolizumab Arm (Arm 
2) of Phase 1b and Phase 2 
DSP-7888 
Dosing 
Emulsion 
Dose Level I 
10.5 mg  
 
 
6 
 
0.1 
 
0.6 
DSP-7888 Dosing Emulsion 
induction phase: weekly for 4 
weeks  
then  
maintenance phase: 
every 2 weeks 
 
nivolumab 
240 mg  
administered IV  
over 30 (±5) minutes 
every  
14 days (2 weeks) in only 
maintenance phase 
 
DSP-7888 Dosing Emulsion 
induction phase: weekly for 
3weeks  
then  
maintenance phase: 
every 3 weeks 
 
pembrolizumab 
200 mg/8mL administered 
IV  
over 30 (±5) minutes  
every  
21 days (3 weeks) in only 
maintenance phase 
 
 
 
DSP-7888 
Dosing 
Emulsion 
Dose Level II 
3.5 mg  
 
 
2 
 
0.1 
 
0.2 
DSP-7888 
Dosing 
Emulsion 
Dose Level III 
(only used for 
dose 
reduction) 
1.75 mg  
 
 
1 
 
0.1 
 
0.1 
Abbreviations: IV = intravenous(ly)  
 


 
 
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8.3. 
Dose Modification 
Any study treatment may be interrupted at any time for any grade toxicity considered intolerable 
by the patient, based on the investigator’s and patient’s judgment.  
In the case of any patient who has missed 4 or more consecutive doses of either study drug, that 
study drug should be permanently discontinued, but the patient may continue on the other 
nonmissed study drug. If the patient is experiencing clinical benefit and, in the opinion of the 
investigator it is in the patient’s best interest to remain on study, the patient may continue 
treatment on a case-by-case basis, after documented discussion with the Sponsor. 
Dose modification by treatment is described in the following sections. 
8.3.1. 
DSP-7888 Dosing Emulsion Dose Modification in Phase 1b 
The dose of DSP-7888 Dosing Emulsion should be held for any Grade 3 or Grade 4 toxicity that 
is related to DSP-7888 Dosing Emulsion and that is present on a scheduled dosing day. Dosing 
may be resumed at a reduced dose once the toxicity has resolved to Grade 1 or less. If the 
toxicity occurs at a dose of 10.5 mg, dosing may resume at the dosage of 3.5 mg. If the toxicity 
occurs at a dose of 3.5 mg, dosing may resume at a dose of 1.75 mg. No intrapatient dose 
reduction is allowed during the DLT evaluation period. 
On days when DSP-7888 Dosing Emulsion is held for toxicity, nivolumab (Arm 1) or 
pembrolizumab (Arm 2) should be administered if scheduled for that day. If toxicities related to 
DSP-7888 Dosing Emulsion preclude administration of DSP-7888 Dosing Emulsion for 
4 consecutive treatments, DSP-7888 Dosing Emulsion should be discontinued; and the medical 
monitor and Sponsor should be consulted for case review and possible approval of continuing 
therapy with nivolumab (Arm 1) or pembrolizumab (Arm 2) alone. 
After the induction phase, dose reduction is permitted due to ISRs if the investigator or 
subinvestigator has judged that a dose reduction is medically required. 
Patients who experience Grade 3 or higher toxicities with a DSP-7888 Dosing Emulsion dose of 
1.75 mg will be removed from the study. 
8.3.2. 
DSP-7888 Dosing Emulsion Dose Modification in Phase 2 
Both dose interruption and dose reductions are allowable for DSP-7888 Dosing Emulsion.  
8.3.2.1. 
Dose Reduction 
After the induction phase, dose reduction to 3.5 mg and subsequently to 1.75 mg is permitted due 
to ISR if the investigator considers that a dose reduction is medically required. No further dose 
reductions from 1.75 mg will be allowed. Re-escalation of the dose after dose reduction is not 
permitted. 
8.3.2.2. 
Dose Interruption 
DSP-7888 Dosing Emulsion must be interrupted for any CTCAE (v.4.03) Grade 3 or 4 AE that 
the investigator considers to be related to DSP-7888 Dosing Emulsion. If toxicity is resolved to 
Grade 1 or less/baseline, the patient may restart treatment with DSP-7888 Dosing Emulsion but 
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EXCEPTION: Because more serious ISRs (eg, Grade 3) may take longer to resolve due to the 
tissue injury, resolution to Grade 2 only is required for restart of treatment with DSP-7888 
Dosing Emulsion. However, no dose reduction is required for following cases: 
• Grade 3 or 4 hematologic laboratory abnormality which resolves to Grade1 or less 
within 7 days without supportive care (blood transfusion or G-CSF agents) 
• Grade 3 or 4 non-hematologic laboratory abnormality which resolves to Grade1 or 
less within 7 days 
• Grade 3 ISR that does not require hospitalization; patients may continue on the study 
treatment per investigator’s judgment 
• Grade 3 fatigue, fever, malaise, edema per CTCAE (v.4.03), which resolves to 
Grade1 or less within 5 days, with appropriate supportive care 
• Grade 3 nausea, vomiting, diarrhea per CTCAE (v.4.03), which resolves within 3 
days, with appropriate supportive care 
Before discontinuation of dosing for any of the above reasons, a conversation with the Medical 
Monitor may be applicable. 
If toxicity is not resolved to Grade 1 or less (or Grade 2 or less in the case of ISRs, as described 
above) within 4 consecutive missing doses and, in the opinion of the investigator, the patient is 
clinically stable and receiving benefit from study drug, the patient may restart treatment with 
DSP-7888 Dosing Emulsion at a reduced dosed on a case-by-case basis, only after consultation 
with the Sponsor. 
8.3.3. 
Pembrolizumab and Nivolumab Dosing Management in Phase 1b and Phase 2 
The product labels/package inserts (refer to pembrolizumab and nivolumab), have identified 
several immune system toxicities as related to the use of pembrolizumab and nivolumab. Dose 
management (dose withholding or permanent discontinuation) should be performed based on the 
recommendations in the respective product label. 
8.3.4. 
Settings and Recommendations for DSP-7888 Dosing Emulsion Injections 
Whenever possible, injections should be administered into the area surrounding the regional 
lymph nodes in the upper arm, the lower abdomen, or the femoral area.   
To the extent possible, injections of study drug should be administered to separate parts of the 
body and separated from one another. Rotation of injection sites is recommended. Injection sites 
should not be chosen in the area of any ongoing skin condition (eg, an area of psoriasis). 
8.3.5. 
Evaluation and Management of Injection Site Reactions 
8.3.5.1. 
Evaluation of Injection Site Reactions 
The type of ISR should be reported for the AE verbatim term (eg injection site redness should be 
reported as injection site redness, and not injection site reaction). Injection site reactions will be 
graded according to CTCAE v4.03 (Table 11). 


 
 
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Table 11: 
Grading of Injection Site Reactions (CTCAE v4.03) 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Tenderness with or without 
associated symptoms (eg, 
warmth, erythema, itching) 
Pain; lipodystrophy; 
edema; phlebitis 
Ulceration or necrosis; 
severe tissue damage; 
operative intervention 
indicated 
Life-threatening 
consequences; urgent 
intervention indicated 
Factors other than the appearance of the ISR should be taken into consideration when evaluating 
the severity of an ISR. A pinpoint ulcer, for example, truly may not be indicative of a Grade 3 
ISR; other factors, such as the presence of fever or the need for systemic analgesia, also should 
be considered in determining ISR severity, and in guiding decisions regarding temporary 
discontinuation and/or dose reductions of DSP-7888 Dosing Emulsion. 
8.3.5.2. 
Management Guidelines for Grade 1 Injection Site Reactions 
Irrigation with physiologic saline is recommended. Topical steroids should be applied as 
appropriate. A mid-strength Class 4 topical steroid is recommended (National Psoriasis 
Foundation, 1996-2020). Examples include: 
• Flurandrenolide ointment, 0.05% 
• Mometasone furoate cream, 0.1% 
• Triamcinolone acetonide cream/spray, 0.1% 
• Fluocinolone acetonide ointment, 0.03% 
• Desoximetasone cream or ointment, 0.05% 
• Hydrocortisone valerate ointment, 0.2% 
Topical antiseptics or antimicrobials that are likely to cause a skin reaction by initiating an 
immune response should not be used; however, antibiotics may be used in the presence of 
infectious findings or positive culture results. 
8.3.5.3. 
Management Guidelines for Grade 2/3 Injection Site Reactions 
• Irrigation with physiologic saline and use of topical steroids, as described for Grade 1 
ISRs above, should be instituted. If topical steroids are not sufficient for ISRs, local 
(subcutaneous) injection of steroids may be considered 
• Topical antibiotics should not be used unless cultures indicate infection 
• Open areas may be protected with a non-stick dressing 
• Patients with Grade 3 ISRs that do not require hospitalization may remain on study 
and receive full dose per investigator’s judgment 
• If an abscess forms, incision and drainage should be carried out to avoid exacerbation 
of the inflammatory response around the site. After the drainage, the site should be 
washed with physiologic saline followed by application of topical steroids, as 
appropriate. Most abscesses should be sterile, but cultures should be obtained (see 
Section 8.3.5.2 for recommendations for when the culture is positive) 


 
 
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• Emergency measures should be implemented for ISRs > Grade 3 
8.4. 
Packaging and Labeling 
 may supply the DSP-7888 bulk product. The study packaging will be performed 
by a contract manufacturing organization designated by 
 
Company).   
 will supply the pembrolizumab (Keytruda - NDC # 0006-3026-02) for Phase 2 of 
the study. It will be delivered to a contract manufacturing organization designated by INC 
Research. 
All packaging and labeling operations will be performed according to Good Manufacturing 
Practice (GMP) for Medicinal Products, Regulatory Requirements for Investigational Drug 
Labeling, and any other relevant regulatory requirements. 
8.5. 
Prior and Concomitant Therapy 
Patients should receive treatment for all inter-current medical conditions or AEs at the discretion 
of the investigator in conformance with community or institutional medical standards. 
All information regarding concomitant treatments (medications or procedures) must be recorded 
on the patient’s case report form/electronic case report form (CRF/eCRF) (including the name of 
the medication or procedure and duration of treatment).  
Palliative and supportive care for disease-related symptoms will be offered to all patients in this 
study. Patients may receive palliative radiation therapy or palliative surgery for symptomatic 
lesion(s) as long as the lesion is not the only evaluable one.  
Study drug administration should be interrupted during and following these therapies until the 
patient has adequately recovered from the effects of treatment, as judged by the treating 
investigator.  
Patients on the study will be permitted to receive COVID-19 vaccinations that are authorized for 
use by the Health Authorities of the country/region. 
If possible, a COVID-19 vaccination should be administered on non-study drug injection days. 
Because DSP-7888 Dosing Emulsion is a peptide vaccine, the COVID-19 vaccine should be 
administered preferably 48 hours after the DSP-7888 Dosing Emulsion administration to avoid 
confounding of immediately occurring AEs. The COVID-19 vaccine should also be given at a 
different injection site from the DSP-7888 Dosing Emulsion injection site. 
8.6. 
Permitted Treatment 
The following medications are allowed:  
• Corticosteroids (equivalent to ≤10 mg/day prednisone; see Appendix 5), and topical, 
ophthalmic, and inhalation corticosteroids are permitted as needed. If a patient 
experiences an immune-related AE (irAE), use of steroids is permitted based on the 
Management of Immunotherapy-related Toxicities (NCCN Guidelines 2018 Version 
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• Medically indicated isolated dosing of steroids for patient with CT IV contrast allergy 
is allowed 
8.7. 
Prohibited Medication/Therapy 
• All other antineoplastic therapy, including cytotoxic agents, hormonal agents, 
monoclonal antibodies, immunomodulatory agents, or investigational agents, with the 
exception of: 
− Luteinizing hormone-releasing hormone (LHRH) agonists, anti-estrogens, or 
aromatase inhibitors started and maintained at a stable dose for at least 90 days 
before the planned first dose of study drug  
• Systemic radiopharmaceuticals during the study 
• Other investigational agents 
• Patients may not receive any immunosuppressive agents, except for irAE 
management, based on the NCCN Guidelines 2018 Version 1 
• Pharmacologic doses of systemic corticosteroids (equivalent to >10 mg/day 
prednisone; see Appendix 5) except for irAE management based on the NCCN 
Guidelines 2018 Version 1. Note: Corticosteroids (equivalent to ≤10 mg/day 
prednisone; see Appendix 5), and topical, ophthalmic, and inhalation corticosteroids 
are permitted, as needed.   
• Treatment aimed at preventing the induction of AEs by the study drug   
• Surgery for the treatment of neoplastic disease. (Note: palliative surgery for 
symptomatic lesion[s] is permitted as long as the lesion is not the only evaluable one.) 
• Radiation therapy for the treatment of neoplastic disease. (Note: palliative radiation 
therapy for symptomatic lesion[s] is permitted.) 
• Hyperthermia/thermotherapy for the treatment of neoplastic disease 
• Patients should not receive live vaccines (eg, Flu-Mist®); vaccines containing killed 
organisms are permitted 
8.8. 
Note on Nivolumab/Pembrolizumab and Systemic 
Immunosuppression  
Nivolumab is a human monoclonal antibody; as such, pharmacokinetic (PK) interaction studies 
have not been conducted. As monoclonal antibodies are not metabolized by cytochrome P450 
enzymes or other drug-metabolizing enzymes, inhibition or induction of these enzymes by 
co-administered medicinal products is not anticipated to affect the PK of nivolumab. As for 
pembrolizumab, no data are available on potential drug interactions.  
The use of systemic corticosteroids and other immunosuppressants at baseline, before starting 
nivolumab or pembrolizumab, should be avoided because of their potential interference with PD 
activity. However, systemic corticosteroids and other immunosuppressants can be used after 
starting nivolumab to treat immune-related adverse reactions. 


 
 
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8.9. 
Treatment Compliance 
The administration of investigational product will occur at the clinical site; therefore, the study 
staff will be able to confirm compliance by maintenance of comprehensive accountability logs 
and pharmacy records. 
8.10. 
Randomization 
Not applicable. 
8.11. 
Blinding 
Not applicable. 


 
 
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9. 
STUDY DRUG MATERIALS AND MANAGEMENT 
Full details on study drug materials and their management are provided in Section 8.1, 
Section 8.2, and Section 8.3. 


 
 
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10. 
PHARMACODYNAMIC AND TUMOR TISSUE ASSESSMENTS 
10.1. 
Tumor Tissue Collection Procedure 
Patients will provide written informed consent before any study-related procedures are 
performed. 
Tumor tissue samples will be collected as specified in Table 7, Table 8, and Table 9.  
For the prestudy evaluation tissue samples, a total of at least 23 slides of archival samples and/or 
the equivalent amount of archival tissue block and/or fresh biopsy samples from the enrolled 
patients are collected. From patients who consent to providing additional samples by signing the 
additional informed consent for these optional samples, an additional 6 to 8 slides will be 
collected for future biomarker analysis.   
10.1.1. 
Phase 1b and Phase 2 
For the post-treatment evaluation tissue samples, from patients who consent to providing 
post-treatment tumor samples by signing additional consent, a tumor sample that will provide 
sufficient material for 23 slides will be obtained. However, if it is not medically feasible to 
collect, less than 23 slides will be acceptable for post-treatment evaluations. From patients who 
consent to providing additional samples by signing the additional informed consent for these 
optional samples, an additional 6 to 8 slides will be collected for future biomarker analysis. The 
time points and circumstances for tumor tissue sample collection for post-treatment evaluations 
are described below: 
At Week 12, a post-treatment evaluation tissue sample will be collected.   
After Week 12, from consenting patients, another post-treatment tissue sample will be collected 
(only applicable for Phase 1b patients), as follows: 
• For patients with SD at Week 12 who receive subsequent response evaluation which 
shows PR, a biopsy will be collected at the time of PR evaluation 
• For patients with suspected pseudo progression at Week 12 who receive subsequent 
response evaluation which shows PR/SD, a biopsy will be collected at the time of 
PR/SD evaluation   
• For patients with PR at Week 12, no further biopsy will be collected   
• For patients with PD/SD at Week 12 who discontinue treatment, no further biopsy 
will be collected   
Tumor tissue samples will be collected at End of Treatment only if the patient discontinues from 
the study prior to Week 12. 
10.1.2. 
Follow-Up Procedures 
The follow-up period will begin once a patient has discontinued the study treatment. The 
follow-up period includes disease assessment follow-up (for patients who discontinue study 
treatment for a reason other than iCPD, per iRECIST) and survival follow-up. 


 
 
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Patients who discontinue study treatment without experiencing iCPD will continue to undergo 
tumor assessment and evaluation of CA-125, according to the SOA, until up to 105 weeks after 
the last dose of study drug, the start of new anticancer therapy, iCPD per iRECIST, death, loss to 
follow-up, withdrawal of consent, or the end of the study, whichever occurs first. 
Patients who discontinue study treatment who are experiencing iCPD per iRECIST with study 
drug, or patients who discontinue study treatment without experiencing iCPD per iRECIST, but 
experience iCPD per iRECIST or start new anticancer therapy during disease follow-up will be 
assessed for survival and new anticancer treatment status per the SOA until up to 24 months after 
the last dose of study drug, death, withdrawal of consent, loss to follow-up, or end of study, 
whichever occurs first.  
10.2. 
Pharmacodynamic Variables (Biomarkers) 
• WT1-specific CTL induction will be measured throughout the study  
• WT1 via CISH, PD-L1 expression status (CPS), and CD8+cell density via IHC 
• TIL and TIS profiling in tumor  
• Mutation status and TMB  
In addition to the biomarkers above, blood samples for serum/PBMC/ct DNA(Plasma) and tumor 
tissue will be collected for future biomarker analysis, only if patients consents for additional 
informed consent(optional). The timing of sample collections will be conducted according to 
Table 7, Table 8, and Table 9. 
When data are available, change from baseline will be estimated and correlated with efficacy 
outcomes. Parameters at baseline obtained from tissue samples will be estimated and correlated 
with efficacy outcomes. 


 
 
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11. 
ASSESSMENTS OF SAFETY AND EFFICACY 
11.1. 
Assessment of Safety 
11.1.1. 
Safety Parameters 
Safety will be evaluated based on the AEs recorded at each contact with the patient, physical 
examinations, and the results of laboratory tests. Toxicity will be graded according to the 
CTCAE v4.03. 
11.1.1.1. Vital Signs 
Vital signs will include systolic and diastolic blood pressures, pulse, respiratory rate, 
temperature, and weight. Blood pressure and heart rate will be recorded in a standardized 
manner, ie, after the patient has rested in the sitting position for at least 5 minutes. Vital signs 
will be recorded according to Table 7, Table 8, and Table 9. Height and body mass index will be 
recorded at Screening only. 
11.1.1.2. Physical Examination 
A physical examination will include examination of the skin; head-ears-eyes-nose-throat 
(HEENT); chest, including the lungs and the heart; abdomen; neurologic, and extremities and 
areas of major lymph node chains. Physical examinations will be conducted according to Table 
7, Table 8, and Table 9. 
Inspection of previous injection sites should be made prior to administration of DSP-7888 
Dosing Emulsion. 
11.1.1.3. Cardiac Assessments 
Cardiac assessments, including ECHO/MUGA scans for ejection fraction; 12-lead resting ECG 
in triplicate, including heart rate, PR interval, QRS duration, QTcF intervals, and ECG findings; 
and pulse oximetry assessments will be obtained during Screening and then according to Table 7, 
Table 8, and Table 9. 
11.1.1.4. Laboratory Assessments 
The hematology and clinical chemistry laboratory analyses will be performed at local 
laboratories. Reference ranges will be supplied and used by the investigator to assess the 
laboratory data for clinical significance and pathologic changes.  
11.1.1.4.1. Hematology 
A complete blood cell count (CBC) will include measures of red blood cells (RBC), hemoglobin 
(Hb), white blood cells (WBC) with differential, and platelet count. A CBC will be performed 
according to Table 7, Table 8, and Table 9.  
11.1.1.4.2. Clinical Chemistry 
Collect samples for serum chemistry tests, including sodium, potassium, calcium, chloride, 
bicarbonate, magnesium, phosphate, ALT, AST, alkaline phosphatase (ALP), creatinine, lactate 


 
 
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dehydrogenase (LDH), gamma-glutamyl transferase (GGT), amylase, CRP (Phase 1b Screening 
only, Phase 2 all visits), albumin, globulin, total bilirubin, conjugated bilirubin, unconjugated 
bilirubin, glucose, cholesterol, triglycerides, blood urea nitrogen (BUN), and uric acid. 
11.1.1.4.3. Thyroid Function Test 
Collect samples for thyroid function tests including thyroid-stimulating hormone (TSH), FT4, 
and T3. 
11.1.1.4.4. Other Laboratory Variables 
Screening for HBsAg, hepatitis C antibody, and HIV will be performed at Screening/Baseline 
only. In cases of negative results, HBsAg with positive hepatitis B core antibody and hepatitis B 
virus DNA testing are required. 
11.1.1.4.5. Urinalysis 
A urinalysis will include measurements of pH, specific gravity, protein, nitrite, glucose, ketones, 
occult blood, bilirubin, and urobilinogen. If any dipstick determinations are 2+ or greater, a 
microscopic examination of urine will be performed. If a dipstick determination of protein is 2+ 
or higher, a 24-hour urine collection must be done. Urine testing will be performed according to 
Table 7, Table 8, and Table 9. 
11.1.1.4.6. Pregnancy Testing 
In Phase 1b, pregnancy testing in women of childbearing potential may be obtained with a serum 
human chorionic gonadotropin test. In Phase 2, pregnancy testing may be obtained via either 
serum or urine testing. A pregnancy test will be performed during Screening and then if 
clinically indicated per the investigator’s judgment. 
11.1.2. 
Adverse and Serious Adverse Events 
11.1.2.1. Definitions 
11.1.2.1.1. Adverse Event 
An AE is any untoward medical occurrence in a clinical study patient administered an 
investigational agent that does not necessarily have a causal relationship with the treatment 
administered. An AE can be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom or disease temporally associated with the use of the investigational 
agent, whether or not considered related to the investigational agent. An AE can arise from any 
use of the drug, and from any route of administration, formulation or dose, including an 
overdose. 
• AEs may be new events or may be pre-existing conditions that have become 
aggravated or have worsened in severity or frequency. 
• AEs may be clinically significant changes from baseline in physical examination, 
laboratory tests, or other diagnostic investigations (eg, laboratory results, x-ray 
findings). See Section 11.1.2.3.5 for further guidance on clinically significant 
laboratory findings. 


 
 
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Pregnancy is not an AE; however, if a female patient or partner of a male patient becomes 
pregnant during the conduct of the study, the Investigator must notify 
 according 
to the procedures provided in Section 11.1.2.4.4. 
11.1.2.1.2. Adverse Reactions and Suspected Adverse Reactions 
All noxious and unintended responses to an investigational agent related to any dose should be 
considered adverse drug reactions. Suspected adverse reactions are any AEs for which there is a 
reasonable possibility that the investigational agent caused the AE. Adverse reactions may also 
include medication errors and uses outside of what is foreseen in the protocol, including misuse, 
abuse, and overdose (intentional or unintentional) of the investigational agent. 
11.1.2.1.3. Serious Adverse Event 
An SAE is any adverse experience occurring at any dose that results in any of the following 
outcomes: 
• Death 
• Life-threatening experience 
− Note: “Life-threatening” refers to a situation in which the patient was at risk of 
death at the time of the event as it occurred; it does not refer to an event that 
might have caused death if it were more severe; 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
the hospitalization is for the following: 
− Elective or pre-planned treatment for a pre-existing condition that is unrelated to 
the indication under study and has not worsened since signing the ICF (as 
documented as medical history on the eCRF). 
− Scheduled therapy for the target disease of the study, including admissions for 
transfusion support or convenience 
• Results in congenital anomaly or birth defect 
• Results in persistent or significant disability or incapacity 
• Is considered to be an important medical event. 
Note: Important medical events are those that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the patient 
or may require intervention to prevent one of the outcomes listed in the definition 
above. Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 


 
 
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11.1.2.2. Procedures for Eliciting, Recording, and Reporting Adverse Events 
11.1.2.2.1. Eliciting and Recording Adverse Events 
Patients will be instructed to report all AEs and will be asked a general health status question at 
each study visit.   
All AEs occurring from the signing of informed consent until 30 days after the last dose of 
investigational therapy will be recorded in the eCRF. Any SAEs related to study-related 
procedures will be collected starting from ICF for biomarkers sampling, blood drawings, and 
biopsy procedures. All SAEs attributable to study-related procedures will be collected starting 
from completion of the Prescreening ICF (biomarkers sampling, blood drawings, and biopsy 
procedures). 
An AE will be followed until it is either resolved, has returned to baseline, or is determined to be 
a stable or chronic condition.   
All SAEs occurring from the signing of informed consent through 30 days after the last 
investigational agent administration will be reported to 
 or designee as outlined in 
Section 11.1.2.3. 
At each required visit during the study, all AEs that have occurred since the previous visit must 
be reviewed. The Investigator or appropriate designee must determine if the AE is serious or 
non-serious.   
11.1.2.2.2. Relationship to Investigational Agent 
A medically qualified Investigator must assess the relationship of any AE to the use of the 
investigational agent, as related or not related, based on clinical judgment and using all available 
information, and may include consideration of the following factors: 
• Possible alternative causes of the AE, including the disease under treatment, pre-
existing conditions, concomitant use of other drugs, and presence of environmental or 
genetic factors. 
• The temporal association between investigational agent exposure and onset of the AE. 
• Whether the manifestations of the AE are consistent with known mechanism of action 
or toxicities associated with the investigational product. 
• Dechallenge: the AE resolved or improved with decreasing the dose or stopping use 
of the investigational agent. Judgment should be used if multiple products are 
discontinued at the same time. 
• Rechallenge: the AE recurred or worsened upon re-exposure to the investigational 
agent. 
The causal relationship between the investigational agent and the AE will be assessed using one 
of the following categories: 
• Not Related/Unrelated: Suggests that there is no causal association between the 
investigational agent and the reported event. 


 
 
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• Unlikely Related: Suggests that the clinical picture is highly consistent with a cause 
other than the investigational agent, but attribution cannot be made with absolute 
certainty and a relationship between the investigational agent and AE cannot be 
excluded with complete confidence. 
• Possibly Related: Suggests that treatment with the investigational agent may have 
caused or contributed to the AE (ie, the event follows a reasonable temporal sequence 
from the time of drug administration and/or follows a known response pattern to the 
investigational agent but could also have been produced by other factors). 
• Probably Related: Suggests that a reasonable temporal sequence of the event with the 
investigational agent administration exists and the likely causal association of the 
event with the investigational agent. This will be based upon the known 
pharmacological action of the investigational agent, known or previously reported 
adverse reactions to the investigational agent or class of drugs, or judgment based on 
the Investigator’s clinical experience. 
• Definitely Related: Temporal relationship to the investigational agent, other 
conditions (concurrent illness, concurrent medication reaction, or 
progression/expression of disease state) do not appear to explain event, corresponds 
with the known pharmaceutical profile, improvement on discontinuation, 
re-appearance on re-challenge. 
11.1.2.2.3. Adverse Event Severity 
The severity of AEs will be assessed according to the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE), v4.03. For events not specifically found in 
CTCAE, the following definitions will be used to estimate grade of severity: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated 
• Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age 
appropriate instrumental activities of daily living (ADL) 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL 
• Grade 4: Life-threatening consequences; urgent intervention indicated 
• Grade 5: Death related to AE 
The term “severe” is often used to describe the intensity (severity) of a specific event (as in mild, 
moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor 
medical significance (such as severe nausea). This is not the same as “serious,” (outlined in 
Section 11.1.2.1.3 which is based on patient/event outcome or action criteria usually associated 
with events that pose a threat to a patient’s life or functioning.  


 
 
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11.1.2.2.4. Assessment of Expectedness 
The Reference Safety Information for assessing the expectedness of an AE in this study is to be 
the section identified as the Reference Safety Information in the most recent DSP-7888 
Investigator’s Brochure.  
The Reference Safety Information for assessing the expectedness of an AE for a comparator or 
co-suspect drug in this study is the US Package Insert for nivolumab or pembrolizumab. 
11.1.2.3. Specific Instructions for Recording Adverse Events on the eCRF 
11.1.2.3.1. Diagnosis Versus Signs and Symptoms 
If a diagnosis is known at the time of reporting, the diagnosis rather than the individual signs and 
symptoms should be recorded in the eCRF (eg, record only hepatitis rather than elevated 
transaminases, bilirubin, jaundice). However, if a constellation of signs and/or symptoms cannot 
be medically characterized as a single diagnosis or syndrome, each individual event should be 
recorded as an AE or SAE on the eCRF. If a diagnosis is subsequently established, it should be 
reported as follow-up and should replace the individual signs and/or symptoms as the event term 
on the eCRF. 
11.1.2.3.2. Adverse Events Occurring Secondary to Other Events 
In general, AEs occurring secondary to other events (eg, clinical sequelae or a cascade of events) 
should be identified by their primary cause. However, medically significant AEs occurring 
secondary to an initiating event that are separated in time should be recorded as independent 
events on the eCRF (eg, dehydration secondary to diarrhea). 
11.1.2.3.3. Medication Errors, Misuse and Abuse of Investigational Agent 
Overdose, medication error, misuse and abuse are defined as follows: 
• Overdose: refers to the administration of a quantity of investigational agent given per 
administration or cumulative, which is above the maximum dose according to the 
protocol. Clinical judgment should always be applied. 
• Medication error: refers to an unintentional error in dispensing or administration of 
the investigational agent not in accordance with the protocol.  
• Off-label use: relates to situations where the investigational agent is intentionally used 
for medical purpose not in accordance with the protocol. 
• Misuse: refers to situations where the investigational agent is intentionally and 
inappropriately used not in accordance with the protocol. 
• Abuse: corresponds to the persistent or sporadic, intentional excessive use of the 
investigational agent, which is accompanied by harmful physical or psychological 
effects. 
• Occupational exposure: refers to the exposure to the investigational agent as a result 
of one’s professional or non-professional occupation. 


 
 
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Overdoses, medication errors, abuse or misuse regardless of whether there was an associated AE 
will be collected as part of investigational agent dosing information and/or as a protocol 
violation, as required.  
Any AE associated with an overdose, medication error, misuse or abuse of study drug should be 
recorded on the AE eCRF with the diagnosis of the AE.   
11.1.2.3.4. Persistent or Recurrent Adverse Events 
A persistent AE is one that extends continuously, without resolution, between patient evaluation 
time points. Such events should only be recorded once on the SAE Report Form and/or the AE 
eCRF. If a persistent AE becomes more severe in severity, it should be recorded as a new AE on 
the eCRF.   
A recurrent AE is one that occurs and resolves between patient evaluation time points, and 
subsequently recurs. Each individual instance of a recurrent AE should be recorded on an SAE 
Report Form and/or AE eCRF. 
11.1.2.3.5. Abnormal Laboratory Values 
If an abnormal laboratory value or vital sign is associated with clinical signs and/or symptoms, 
the sign or symptom should be reported as an AE or SAE, and the associated laboratory value or 
vital sign should be considered additional information that must be recorded on the relevant 
eCRF. If the laboratory abnormality is a sign of a disease or syndrome, only the diagnosis needs 
to be recorded on the SAE Report Form and/or eCRF. Abnormal laboratory values assessed as 
not clinically significant (NCS) should be documented as such in the source document. 
Abnormal laboratory values will be reported as an AE if the laboratory result: 
• Requires an adjustment in the investigational agent(s) or discontinuation of treatment 
• Meets seriousness criteria 
• Requires additional testing or surgical intervention 
• Is associated with accompanying symptoms 
11.1.2.3.6. Cancers 
The development of a new primary cancer should be regarded as an AE and will generally meet 
at least one of the serious criteria (see Section 11.1.2.1.3). New primary cancers are those that 
are not the primary reason for the administration of the study treatment and have developed after 
the inclusion of the patient into the study. They do not include metastases of the original cancer. 
Symptoms of metastasis or the metastasis of the disease under study should not be reported as an 
AE/SAE, as they are considered to be disease progression. 
11.1.2.3.7. COVID-19 
Because much is still unknown about how SARS-CoV-2 affects the human body, patients who 
have tested positive for COVID-19 will be identified and relevant information collected. All 
patients should provide documentation of any testing for COVID-19, if available, along with the 
test results, at screening for enrollment and/or during the study. Prior test results should be 
reported, if available, for any patient who has previously tested positive for COVID-19 


 
 
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SARS-CoV-2 titers (antiviral immunoglobulin G [IgG] and immunoglobulin M [IgM]). These 
data will be entered into the patient’s study-specific record. 
Any patient-reported illness of COVID-19 during the study should be recorded as an AE. If a 
patient reports infection with COVID-19, the investigator may discuss with the Medical Monitor 
whether the patient can continue on study. 
11.1.2.3.8. Deaths 
All events leading to the clinical outcome of death occurring during the SAE reporting period 
(from the signing of the informed consent through 30 days after the last investigational agent 
administration) are to be reported to Sponsor or designee as an SAE and recorded on the AE 
eCRF. 
11.1.2.4. Reporting of Expedited Safety Observations by the Investigator Including 
Serious Adverse Events 
11.1.2.4.1. Immediate Reporting of Serious Adverse Events by Investigator to Sponsor 
All SAEs, from the signing of informed consent through 30 days after last dose, including SAEs 
from screen failures, will be reported to the Sponsor or designee within 24 hours of the 
Investigator’s first knowledge of the event, even if the experience does not appear to be related 
to the investigational agent.  
Serious AEs should be communicated on an SAE report form as follows: 
 Pharmacovigilance Department Contacts 
Email: 
 
Fax: 
 
The initial SAE report must be as complete as possible, including details of the current illness 
and SAE, and an assessment of the causal relationship between the event and the investigational 
product(s). Information not available at the time of the initial report (eg, an end date for the AE, 
laboratory values received after the report, or hospital discharge summary) must be documented 
on a follow-up form. All follow-up information must be reported in the same timelines as initial 
information. 
At any time after completion of the AE reporting period (ie, 30 days post-treatment), if an 
Investigator becomes aware of an SAE that is suspected by the Investigator to be related to the 
investigational agent, the event must be reported to the Sponsor or designee. 
11.1.2.4.2. Immediate Reporting of Occupational Exposure, Overdose, or New Cancers 
Any occupational exposure or exposure of an individual not enrolled in the study to the 
investigational medicinal product must be reported to the Sponsor or designee within 24 hours 
of the Investigator's first knowledge of the event, even if the exposure does not result in an AE. 
Unintentional exposures should be communicated on the SAE Report Form, as described above 
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Any overdose to the investigational medicinal product must be reported to the Sponsor or 
designee within 24 hours of the Investigator's first knowledge of the event, even if the overdose 
does not result in an AE. Overdose should be communicated on the SAE Report Form, as 
described above for SAEs. 
Any new cancers must be reported to Sponsor or designee within 24 hours of the Investigator's 
first knowledge of the event. New cancers should be communicated on the SAE Report Form, as 
described above for SAEs. 
11.1.2.4.3. Reporting COVID-19 Infections 
Suspected or confirmed COVID-19 infections, including asymptomatic infections and positive 
COVID-19 tests are Adverse Events of Special Interest (AESIs) and therefore immediately 
reportable events, even if the events do not meet SAE criteria. 
Serious COVID-19 events will be reported on an SAE Report form within 24 hours of the 
investigator’s awareness, according to Section 11.1.2.4.1. 
Nonserious COVID-19 events will be reported on a COVID-19 Report form within 5 calendar 
days of the investigator’s awareness, to the same email/fax for reporting SAEs described in 
Section 11.1.2.4.1. 
Updates or follow-up information for COVID-19 events should be reported on an SAE Report 
form (serious events) or a COVID-19 Report form (nonserious events) within the same timelines 
as the initial reports. 
11.1.2.4.4. Reporting Pregnancies 
If a female patient or the female partner of a male patient becomes pregnant during the course of 
study, the Investigator must report the pregnancy to the Sponsor or designee using the 
Pregnancy Reporting Form within 24 hours of becoming aware of the event. 
If not all information on the Pregnancy Reporting Form is available at the time of the initial 
report, follow-up Pregnancy reports will be completed and submitted within 24 hours of 
becoming aware of the new information. The Investigator is required to follow up on the 
pregnancy until it has completed. The outcome of the pregnancy and the status of the newborn (if 
applicable) will be reported on the Pregnancy Reporting Form within 24 hours of becoming 
aware. SAEs associated with the pregnancy, including fetal death, miscarriage or congenital 
anomalies, must be reported as a serious adverse event according to Section 11.1.2.4. 
If the female partner of a male patient becomes pregnant, the Investigator must obtain consent to 
collect pregnancy information from the pregnant partner (including the status of the newborn, if 
applicable). 
11.1.2.4.5. Expedited Reporting by the Sponsor to a Regulatory Health Authority 
The Sponsor will manage the expedited reporting of relevant safety information to concerned 
health authorities, competent authorities, and IRBs/IECs in accordance with local laws and 
regulations. 


 
 
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11.1.2.4.6. Safety Notifications by the Sponsor to the Investigator 
Investigators will receive prompt notification of any suspected adverse drug reaction that is both 
serious and unexpected, or any finding that suggests a significant risk for patients, in accordance 
with local laws and regulations. The Investigator will promptly inform his/her IRB/IEC of the 
notification and insert the notification in the Investigator’s Regulatory Binder in accordance with 
local regulations. 
11.2. 
Assessment of Efficacy 
Tumor response will be determined by the investigator according to RECIST v1.1 and iRECIST. 
Tumor response according to iRECIST will be used for treatment decision-making and other 
supporting disease-specific efficacy measurements. Tumor evaluations during treatment period 
in Arm 1 will be performed at Weeks 4, 12, 18, and 24, followed by every 12 weeks until disease 
progression. Tumor evaluations during treatment period in Arm 2 will be at Weeks 6, 12, 18, and 
24, followed by every 12 weeks until disease progression.  
Tumor evaluations during the treatment period in Phase 2 will be at Weeks 6, 12, 18, and 24, 
followed by every 12 weeks until disease progression or the completion of 35 treatment cycles. 
Patients who discontinue study treatment without experiencing iCPD will continue to undergo 
tumor assessment according to the SOA until up to 24 months after the last dose of study drug, 
the start of new anticancer therapy, iCPD per iRECIST, death, loss to follow-up, withdrawal of 
consent, or the end of the study, whichever occurs first. 


 
 
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12. 
STATISTICS 
12.1. 
Statistical Methods 
Detailed methodology for the statistical analyses of the data collected in this study will be 
documented in the statistical analysis plan (SAP), which will be maintained by 
 
The SAP may modify the plans outlined in the protocol; however, any major modifications of the 
primary endpoint definition and/or its analysis will also be reflected in a protocol amendment. 
In general, all efficacy and safety endpoints will be analyzed using descriptive statistics (n, 
mean, standard deviation, median, and ranges for continuous variables; frequencies and 
percentages for categorical variables).  
All deviations related to conduct of the study, patient management, or patient assessment will be 
identified, evaluated, and closed before database lock and will be described in the final CSR. 
Protocol deviations are not allowed for inclusion or exclusion criteria. 
12.1.1. 
Determination of Sample Size 
12.1.1.1. Dose-search Part (Phase 1b) 
In the dose-search part of the study, there will be 6 to 12 patients for each arm (up to a total of 
24 patients). If a patient is terminated before having any evaluable data, the patient will be 
replaced until the planned sample size is reached.  
In the enrichment cohort, 10 patients will be enrolled to help evaluate the preliminary antitumor 
activity and the safety profile of DSP-7888 Dosing Emulsion.  
If anti-tumor activities are observed in any tumor type, additional patients may be enrolled for 
further assessment.  
12.1.1.2. Dose-Expansion Part (Phase 2) 
There is no formal hypothesis testing for the Phase 2 cohort. Approximately 40 eligible PROC 
patients are expected to be enrolled in the Phase 2 dose expansion part of the study. A Bayesian 
decision-making framework will be employed to quantify whether proof of concept (POC) can 
be established based on the overall response rate (ORR) by Week 24 from the final analysis for 
overall population and/or CPS < 10 subpopulation. The POC is established at the final analysis if 
either or both of the following two conditions are met:  
• In the overall population, 70% credible interval of ORR with 10% in the left tail and 
20% in the right tail will be calculated: if lower bound ≥ 8% and upper bound ≥ 21% 
(where 8% is the reference value [Section 4.3.1; Matulonis, 2019]) and 21% is the 
target value of ORR in the overall population), the study achieve POC.   
• In the CPS< 10 subpopulation, 50% credible interval of ORR with 20% in the left tail 
and 30% in the right tail will be calculated: if lower bound ≥ 5% and upper bound 
≥ 15% (where 5% is the reference value [Section 4.3.1; Matulonis, 2019] and 15% is 
the target value of ORR in CPS < 10 subpopulation), the study achieves POC.  


 
 
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Statistical analysis may be conducted to evaluate the relationship between ORR and the PD-L1 
level and/or WT1 using statistical methods, such as ROC curve or contingency table.  
In Phase 2 of the study, approximately 40 patients will be enrolled. Additional patients may be 
enrolled to further assess anti-tumor activities in the subgroups of interest. However, the total 
sample size of Phase 2 cannot exceed 60 patients. In total, approximately 64-84 patients will be 
enrolled in the study. 
12.1.2. 
Analysis Datasets 
12.1.2.1. Full Analysis Set 
The Full Analysis Set (FAS) consists of all patients who receive at least 1 full or partial dose of 
study treatment (DSP-7888 Dosing Emulsion, nivolumab, or pembrolizumab). Patients will be 
classified according to the treatment assigned (dose level and schedule). 
Patients who were screened but never started treatment will be listed but not included in the 
FAS. Screening failures will not be included in any of the summary tables. 
12.1.2.2. Safety Set 
The Safety Set (SS) consists of all patients who receive at least 1 full or partial dose of study 
treatment (DSP-7888 Dosing Emulsion, nivolumab, or pembrolizumab). Patients will be 
classified according to the treatment received (dose level and schedule), where treatment 
received is defined as the assigned treatment if the patients took at least 1 dose of that treatment 
or the first treatment received if the assigned treatment was never received. 
12.1.2.3. Dose-Determining Set  
The DDS includes all patients from the FAS (Phase 1b, dose-search part only) who met the 
minimum exposure criterion and had sufficient safety evaluations or experienced a DLT during 
in the first 2 cycles of treatment.  
A patient is considered to have met the minimum exposure criterion if he/she received at least 
50% of the planned doses of DSP-7888 Dosing Emulsion (≥3 doses) and 
nivolumab/pembrolizumab (≥1 dose) during the first 2 cycles. 
Patients who do not experience a DLT during the first 2 cycles are considered to have sufficient 
safety evaluations if they have been observed for 2 cycles after the first dose, and are considered 
by both the Sponsor and investigators to have enough safety data to conclude that a DLT did not 
occur. 
12.1.2.4. Efficacy Set  
The Efficacy Set (ES) includes all patients from the FAS who have responded to treatment 
(CR/PR), assessed as progressed on treatment without regard to length of treatment, or have been 
on treatment for 6 months or more without regard to tumor response status. 
12.1.3. 
Handling of Missing Data 
No missing data will be imputed, except missing start/end date of concomitant medication. The 
rule of imputation will be defined in the SAP. 


 
 
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12.1.4. 
Demographic and Baseline Characteristics 
Baseline is defined as the last non-missing measurement taken before receiving the first dose of 
study drug. All applicable demographic and baseline characteristics will be summarized with 
descriptive statistics. 
12.1.5. 
Data Analyses 
12.1.5.1. Efficacy Analysis  
Kaplan-Meier methods will be used to summarize time-to-event endpoints (OS, PFS, and DOR). 
Primary efficacy of ORR will be analyzed using the Bayesian approach defined in the SAP; 
other efficacy analyses will be performed on the FAS.  
Patient responses will be assessed based on RECIST v1.1 and iRECIST. Data listings and 
summaries may include tumor markers, additional imaging, or other response data. Potential 
relationships between PD and other response data may be evaluated. In Phase 2, primary efficacy 
of ORR will be analyzed using the Bayesian approach defined in the SAP; other efficacy 
analyses will be performed on the FAS. 
Progression-free survival ratio (PFSr) will be summarized for both the Phase 1b enrichment 
cohort and for Phase 2.   
12.1.5.2. Safety Analysis 
Adverse events will be assessed according to CTCAE v4.0,3 when appropriate, and will be 
evaluated by grade and System Organ Class (SOC). Adverse event listings and tabulated 
summaries of categorized AEs will be generated by dose level and patients overall, for each 
study arm, and study phase. Additionally, the number of patients enrolled, number evaluable for 
dose search, and number with DLTs will be described for each dose level, by patients overall, 
and for each study arm in Phase 1b, the dose-search part of the study. Vital signs, laboratory 
data, and ECG data stratified by dose level and overall for each study arm and phase will be 
summarized for changes over time at each post-baseline visit, together with the change from 
baseline.   
12.1.5.3. Pharmacodynamics, Biomarkers, and Exploratory Analysis 
Additional antitumor activity will be evaluated on an exploratory basis and will be summarized 
using descriptive statistics. Analyses will be performed both for all patients enrolled and for 
patients evaluable for response in the FAS. Data listings and summaries may include tumor 
markers, additional imaging, or other response data. Potential relationships between drug 
administration, PD, and other response data may be evaluated. Kaplan-Meier estimates of OS 
and PFS will be generated. 
All exploratory analyses intended to be discussed in the Clinical Study Report (CSR) will be 
defined in the SAP. The biomarker data will be listed and summarized by treatment and tumor 
type, where possible. Correlation with the efficacy data may be explored by statistical methods 
and graphic presentation. The details of the analysis will be described in the SAP. Additional 
analyses may be performed on a program or company level. These will be planned and reported 
separately from this study. 


 
 
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12.1.5.4. Interim Analysis 
No formal interim analysis is planned. However, safety will be reviewed on an ongoing basis for 
the dose-search part (Phase 1b).  
In Phase 2, the interim monitoring analysis will be conducted using Bayesian method and start 
after the first 20 patients have response evaluation or withdraw or die by Week 24 for futility and 
early efficacy assessment.  
• If the posterior probability of ORR ≥ 21% in overall population is≤ 2.5% AND the 
posterior probability of ORR ≥ 15% in CPS < 10 subpopulation is ≤ 2.5%, the study 
is futile and further enrollment will be stopped. 
• If the posterior probability of ORR ≥ 21% in overall population is ≥ 80% AND the 
posterior probability of ORR ≥ 15% in CPS < 10 subpopulation is ≥ 70%, then early 
succeed met and further enrollment may be stopped.   
• Otherwise, the enrollment will continue as is until 40 patients.  
The above decision rules for interim analysis are non-binding.  


 
 
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13. 
DIRECT ACCESS TO SOURCE DATA/DOCUMENTS 
13.1. 
Study Monitoring 
Data for each patient will be recorded on a CRF. Data collection must be completed for each 
patient who signs an ICF and is administered study drug. Screen failures will not have completed 
CRFs, but the site is to maintain all signed ICF and medical records, as well as documentation of 
the reason for screen failure. 
In accordance with current Good Clinical Practice (cGCP) and International Council on 
Harmonisation (ICH) of Technical Requirements for Pharmaceuticals for Human Use guidelines, 
the study monitor will carry out source document verification at regular intervals to ensure that 
the data collected in the CRF are accurate and reliable.  
The investigator must permit the monitor, the IEC/IRB, the Sponsor’s internal auditors, and 
representatives from regulatory authorities direct access to all study-related documents and 
pertinent hospital or medical records for confirmation of data contained within the CRFs.  
During the COVID-19 public health emergency, traditional on-site monitoring might be difficult 
for reasons such as: (1) sites may not be able to accommodate monitoring visits (eg, due to 
staffing limitations or site closures) or (2) monitors may not be able to travel to trial sites. When 
planned on-site monitoring visits are not possible, the reason should be documented and 
available for review by 
 and during FDA inspections. On-site monitoring visits 
may be replaced with remote monitoring visits during the COVID-19 public health emergency 
(Food and Drug Administration, January 2021). 
13.2. 
Audits and Inspections 
Study centers and study documentation may be subject to a Quality Assurance audit during the 
course of the study by the Sponsor or its nominated representative. In addition, inspections may 
be conducted by regulatory authorities at their discretion. 
13.3. 
Institutional Review Board/Independent Ethics Committee 
The investigator must obtain IRB or IEC approval for the study. Initial IRB/IEC approval of the 
protocol and all materials approved by the IRB/IEC for this study, including the patient ICF and 
any recruitment materials must be maintained by the study site/investigator and made available 
for inspection by the study monitor or any regulatory authorities with an interest in this study. 


 
 
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14. 
QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure compliance with Good Clinical Practices and all applicable regulatory requirements, 
 may conduct a quality assurance audit. Refer to Section 13.2 for more details 
regarding the audit process 


 
 
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15. 
ETHICS 
15.1. 
Ethics Review 
The Principal Investigator must obtain IRB approval for the investigation. Initial IRB approval, 
and all materials approved by the IRB for this study including the patient consent form and 
recruitment materials must be maintained by the Investigator and made available for inspection. 
The final study protocol, including the final version of the Informed Consent Form, must be 
approved or given a favorable opinion in writing by an IRB or IEC as appropriate. The 
investigator must submit written approval to 
 before he or she can enroll any 
patient/subject into the study. 
The Principal Investigator is responsible for informing the IRB or IEC of any amendment to the 
protocol in accordance with local requirements. In addition, the IRB or IEC must approve all 
advertising used to recruit patients for the study. The protocol must be re-approved by the IRB or 
IEC upon receipt of amendments and annually, as local regulations require. 
The Principal Investigator is also responsible for providing the IRB with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product. 
 will provide this information to the Principal Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. 
15.2. 
Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH Good Clinical Practice, applicable 
regulatory requirements and the 
 policy on Bioethics. 
15.3. 
Informed Consent 
The Principal Investigator(s) at each site will ensure that the patient is given full and adequate 
oral and written information about the nature, purpose, possible risk and benefit of the study. 
Patients must also be notified that they are free to discontinue from the study at any time. The 
patient should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The patient’s signed and dated informed consent must be obtained before conducting any study 
procedures. If an informed consent cannot be obtained and documented from a prospective trial 
participant (or legally authorized representative) as signed paper copy, the consent form may be 
provided electronically by the Investigator/designee.  
Where a prospective trial participant (or legally authorized representative) is unable to print the 
informed consent document provided electronically by the Investigator/designee, an electronic 
signature process is not available, and the prospective trial participant must meet time-sensitive 
eligibility criteria, the investigator may consider using the alternative process to satisfy FDA 
requirements for obtaining and documenting informed consent and IRB approved process Food 
and Drug Administration, January 2021). 


 
 
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The Principal Investigator(s) must maintain the original, signed Informed Consent Form. A copy 
of the signed Informed Consent Form must be given to the patient. 


 
 
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16. 
DATA HANDLING AND RECORDKEEPING 
16.1. 
Data Protection 
Monitors, auditors, and other authorized agents of the Sponsor and/or its designee, the 
IEC(s)/IRB(s) approving this research, and the FDA, as well as that of any other applicable 
agency(ies), will be granted direct access to the study patients’ original medical records for 
verification of clinical study procedures and/or data, without violating the confidentiality of the 
patients to the extent permitted by the law and regulations. In any presentations of the results of 
this study or in publications, the patients’ identity will remain confidential. 
All personal data collected and processed for the purposes of this study should be managed by 
the investigator and his/her staff, with adequate precautions to ensure confidentiality of those 
data; and in accordance with the Health Insurance Portability and Accountability Act, as well as 
national and/or local laws and regulations applicable to personal data protection.  
If applicable, the Sponsor will provide CT/MRI scans for potential central independent radiology 
assessment.   
16.2. 
Source Documents 
The Sponsor or 
) will be responsible for 
activities associated with the data management of this study. This will include setting up a 
relevant database and data transfer mechanisms, along with appropriate validation of data and 
resolution of queries. Data generated within this clinical study will be handled according to the 
relevant standard operating procedures (SOPs) of the data management and biostatistics 
departments of the Sponsor or 
). 
Study centers will enter data directly into an electronic data capture (EDC) system by completing 
the CRF via a secure internet connection. Data entered into the eCRF must be verifiable against 
source documents at the study center. Data to be recorded directly on the eCRF will be 
identified, and the eCRF will be considered the source document. Any changes to the data 
entered into the EDC system will be recorded in the audit trail and will be compliant with 
CFR 21 Part 11. 
Medical coding will use Medical Dictionary for Regulatory Activities (MedDRA) for 
concomitant diseases and AEs and the World Health Organization (WHO) Drug Dictionary for 
medications. 
Missing or inconsistent data will be queried in writing to the investigator for clarification. 
Subsequent modifications to the database will be documented. 
16.3. 
Inspection of Records 
 will be allowed to conduct site visits to the investigation facilities for the purpose 
of monitoring any aspect of the study. The Investigator agrees to allow the monitor to inspect the 
drug storage area, study drug stocks, drug accountability records, subject charts and study source 
documents, and other records relative to study conduct. If on-site monitoring visits are not 
possible 
 will be allowed to do remote monitoring to maintain oversight of the 
clinical site. 


 
 
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16.4. 
Retention of Records 
The Principal Investigator must maintain all documentation relating to the study for a period of 
2 years after the last marketing application approval, or if not approved 2 years following the 
discontinuance of the test article for investigation. If it becomes necessary for 
 or 
the Regulatory Authority to review any documentation relating to the study, the Investigator 
must permit access to such records. 


 
 
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17. 
PUBLICATION POLICY 
The publication policy for the study will be described in the clinical study agreement. To avoid 
disclosures that could jeopardize proprietary rights, the investigator agrees to give 
 
 the right to review all manuscripts, abstracts, and presentations related to this study 
prior to their submission for publication or presentation. 
 may use these data now 
and in the future for presentation or publication at 
 discretion or for submission 
to government regulatory agencies.  
Authorship among Investigators generally will be based on the extent of significant contribution, 
including scientific and clinical, to the publication. 


 
 
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18. 
LIST OF REFERENCES 
American Cancer Society, Cancer Facts and Figures 2017. 
https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-
cancer-facts-and-figures/2017/cancer-facts-and-figures-2017.pdf. Accessed 28 Jun 2017. 
Cao K, Hollenbach J, Shi X, Shi W, Chopek M, Fernández-Viña MA. Analysis of the 
frequencies of HLA-A,B, and C alleles and haplotypes in the five major ethnic groups of the 
United States reveals high levels of diversity in these loci and contrasting distribution patterns in 
these populations. Hum Immunol. 2001;62:1009-1030. 
Davis A, Tinker AV, Friedlander M. "Platinum resistant" ovarian cancer: what is it, who to treat 
and how to measure benefit? Gynecol Oncol. 2014;133:624-631. 
Goldstein NS, Uzieblo. WT1 immunoreactivity in uterine papillary serous carcinomas is 
different from ovarian serous carcinomas. Am J Clin Pathol. 2002;117(4):541-545. 
Goto M, Nakamura M, Suginobe N, et al. DSP-7888, a novel cocktail design of the WT1 peptide 
vaccine, and its combinational immunotherapy with an immune checkpoint-blocking antibody 
against PD-1. ASH Annual Meeting 2016;(Abs 4715). 
Hwang H, Quenneville L, Yaziji H, Gown AM. Wilms tumor gene product: sensitive and 
contextually specific marker of serous carcinomas of ovarian surface epithelial origin. Appl 
Immunohistochem Mol Morphol. 2004;12(2):122-126. 
Jiang X, Li W, Li X, Bai H, Zhang Z. Current status and future prospects of PARP inhibitor 
clinical trials in ovarian cancer. Cancer Manag Res. 2019;11:4371-4390.  
Kaida M, Morita-Hoshi Y, Soeda A, et al. Phase 1 trial of Wilms Tumor 1 (WT1) peptide 
vaccine and gemcitabine combination therapy in patients with advanced pancreatic or biliary 
tract cancer. J Immunother. 2011;34(1):92-99. 
Köbel M, Kalloger SE, Huntsman DG, et al. Differences in tumor type in low-stage versus 
high-stage ovarian carcinomas. Int J Gynecol Pathol. 2010;29(3):203-211.  
Manlove LS, Schenkel JM, Manlove KR, et al. Heterologous vaccination and checkpoint 
blockade synergize to induce antileukemia Immunity. J Immunol. 2016;196(11):4793-4804. 
Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, et al. 
Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian 
cancer: results from the phase II KEYNOTE-100 study. Ann Oncol. 2019;30:1080-1087. 
McCluggage WG, Judge MJ, Clarke BA, et al. Data set for reporting of ovary, fallopian tube and 
primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer 
Reporting (ICCR). Mod Pathol. 2015;28:1101-1122. 
Miyakoshi S, Usuki K, Matsumura I, et al. Preliminary results from a phase 1/2 trial of DSP-
7888, a novel WT1 peptide-based vaccine for patients with myelodysplastic syndrome (MDS). 
ASH Annual Meeting 2016;(Abs 4335). 
Morse MA, Lyerly HK. Checkpoint blockade in combination with cancer vaccines. Vaccine. 
2015;33:7377-7385. 


 
 
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National Comprehensive Cancer Network Guidelines. 
https://www.nccn.org/professionals/physician_gls/default.aspx. Accessed October 2019. 
National Psoriasis Foundation. https://www.psoriasis.org/potency-chart/. Accessed 
01September2020. 
Oka Y, Tsuboi A, Taguchi T, et al. Induction of WT1 (Wilms' tumor gene)-specific cytotoxic T 
lymphocytes by WT1 peptide vaccine and the resultant cancer regression. Proc Natl Acad Sci 
USA. 2004;101(38):13885-13890. 
Patsoukis N, Weaver JD, Strauss L, Herbel C, Seth P, Boussiotis VA. Immunometabolic 
Regulations Mediated by Coinhibitory Receptors and Their Impact on T Cell Immune 
Responses. Front Immunol. 2017 Apr 11;8:330. 
Pauken KE, Godec J, Odorizzi PM, Brown KE, Yates KB, Ngiow SF, Burke KP, Maleri S, 
Grande SM, Francisco LM, Ali MA, Imam S, Freeman GJ, Haining WN, Wherry EJ, Sharpe 
AH. The PD-1 Pathway Regulates Development and Function of Memory CD8+ T Cells 
following Respiratory Viral Infection. Cell Rep. 2020 Jun 30;31(13):107827. 
Sakai K, Shimadaira S, Maejima S, et al. Dendritic cell-based immunotherapy targeting Wilms’ 
tumor 1 in patients with recurrent malignant glioma. J Neurosurg. 2015;123(4):989-997. 
Seidman JD, Horkayne-Szakaly I, Haiba M, et al. Int J Gynecol Pathol. 2004;23(1):41-44. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. The histologic type and stage 
distribution of ovarian carcinomas of surface epithelial origin. CA Cancer J Clin. 2018;2-18; 
68:7-30.  
Soeda A, Morita-Hoshi Y, Kaida M, et al. Long-term administration of Wilms Tumor-1 peptide 
vaccine in combination with gemcitabine causes severe local skin inflammation at injection sites. 
Jpn J Clin Oncol. 2010;40(12):1184-1188. 
Torre LA, Trabert B, DeSantis CE, et al. Ovarian Cancer Statistics, 2018. CA Cancer J Clin. 
2018;68(4):284-296. 
Verma V, Shrimali RK, Ahmad S, Dai W, Wang H, Lu S, Nandre R, Gaur P, Lopez J, Sade-
Feldman M, Yizhak K, Bjorgaard SL, Flaherty KT, Wargo JA, Boland GM, Sullivan RJ, Getz G, 
Hammond SA, Tan M, Qi J, Wong P, Merghoub T, Wolchok J, Hacohen N, Janik JE, 
Mkrtichyan M, Gupta S, Khleif SN. PD-1 blockade in subprimed CD8 cells induces 
dysfunctional PD-1+CD38hi cells and anti-PD-1 resistance. Nat Immunol. 2019 Sep;20(9):1231-
1243. 
World Health Organization web site. http://www.who.int/cancer/en/. Accessed 28 Jun 2017: 
 
 


 
 
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19. 
APPENDICES 
Performance Status Scores 
Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) 
Immune Response Evaluation Criteria in Solid Tumors (iRECIST) 
CA-125 Gynecologic Cancer Inter Group Criteria 
Glucocorticoid Dose Equivalents 
Common Terminology Criteria for Adverse Events (CTCAE) 4.03 
Study Design Flow 
Investigator Signature Page 


 
 
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APPENDIX 1. EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS SCORES 
ECOG Performance Status Scale 
Grade 
Descriptions 
0 
Normal activity. Fully active, able to carry on all pre-disease performance 
without restriction. 
1 
Symptoms, but ambulatory. Restricted in physically strenuous activity, but 
ambulatory and able to carry out work of a light or sedentary nature (eg, 
light housework, office work). 
2 
In bed < 50% of the time. Ambulatory and capable of all self-care, but 
unable to carry out any work activities.  Up and about more than 50% of 
waking hours. 
3 
In bed > 50% of the time.  Capable of only limited self-care, confined to bed 
or chair more than 50% of waking hours. 
4 
100% bedridden.  Completely disabled.  Cannot carry on any self-care.  
Totally confined to bed or chair. 
5 
Dead. 
 
 ECOG = Eastern Cooperative Oncology Group. 
 
 


 
 
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APPENDIX 2. RESPONSE EVALUATION CRITERIA IN SOLID 
TUMORS  
Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), will be used by local 
site Investigators to assess tumor response and progression and make treatment decisions. 
https://ctep.cancer.gov/protocoldevelopment/docs/recist_guideline.pdf 
 
Treatment decision 
 
If a patients experiences objective disease progression according to RECIST (v 1.1) and is 
clinically stable, patients will continue on treatment with study drug until patients experiences 
immune confirmed PD (iCPD) per iRECIST. 
 
Clinical Stability is defined as: 
-No worsening of performance status 
-No clinically relevant increase in disease-related symptoms 
-No requirement for intensified management of disease-related symptoms (such as analgesics, 
radiation, or palliative care)  
 
Patients who remain on study treatment following objective disease progression per RECIST 
(v.1.1) will continue to be evaluated for objective response to study treatment according to the 
SOA and evaluated according to iRECIST 
 
Summary: 
Evaluation of Target Lesions 
Complete Response (CR):  Disappearance of all target lesions.  Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm. 
Partial Response (PR):  At least a 30% decrease in the sum of the diameters of target lesions, 
taking as reference the baseline sum diameters. 
Progressive Disease (PD):  At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the 
smallest on study).  In addition to the relative increase of 20%, the sum must also demonstrate an 
absolute increase of at least 5 mm.  (Note:  the appearance of one or more new lesions is also 
considered progression). 


 
 
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Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest sum diameters while on study. 
Evaluation of Non-Target Lesions 
Complete Response (CR):  Disappearance of all non-target lesions and normalization of tumor 
marker level.  All lymph nodes must be non-pathological in size (< 10 mm short axis). 
Note:  If tumor markers are initially above the upper normal limit, they must normalize for a 
patient to be considered in complete clinical response. 
Non-CR/Non-PD:  Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits. 
Progressive Disease (PD):  Appearance of one or more new lesions and/or unequivocal 
progression of existing non-target lesions.  Unequivocal progression should not normally trump 
target lesion status.  It must be representative of overall disease status change, not a single lesion 
increase. 
Although a clear progression of “non-target” lesions only is exceptional, the opinion of the 
treating physician should prevail in such circumstances; and the progression status should be 
confirmed at a later time by the review panel (or Principal Investigator). 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until 
disease progression/recurrence (taking as reference for progressive disease the smallest 
measurements recorded since the treatment started).  The patient's best response assignment will 
depend on the achievement of both measurement and confirmation criteria. 
RECIST Response for Patients with Measurable Disease (ie, Target Disease) 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall 
Response 
Best Overall Response 
when Confirmation is 
Required* 
CR 
CR 
No 
CR 
> 4 wks. Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
> 4 wks. Confirmation** 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/Non-
PD/not evaluated 
No 
PR 


 
 
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Target Lesions 
Non-Target Lesions 
New Lesions 
Overall 
Response 
Best Overall Response 
when Confirmation is 
Required* 
SD 
Non-CR/Non-
PD/not evaluated 
No 
SD 
Documented at least once 
> 6 weeks from 
baseline** 
PD 
Any 
Yes or No 
PD 
No prior SD, PR or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations:  CR = complete response; PD = progressive disease; PR = partial response; SD = stable disease. 
*See RECIST v1.1 publication for further details on what is evidence of a new lesion. 
**Only for non-randomized trials with response as primary endpoint. 
***In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as disease 
progression. 
Note:     Patients with a global deterioration of health status requiring discontinuation of treatment without objective 
evidence of disease progression at that time should be reported as “symptomatic deterioration.”  Every effort should 
be made to document the objective progression even after discontinuation of treatment. 
 
RECIST Response for Patients with Non-Measurable Disease (ie, Non-Target Disease) 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
Abbreviations: CR = complete response; PD = progressive disease 
*‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly used as an 
endpoint for assessment of efficacy in some trials so to assign this category when no lesions can be measured is 
not advised 
 
 


 
 
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APPENDIX 3. IMMUNE-RESPONSE EVALUATION CRITERIA IN 
SOLID TUMORS (IRECIST) 
iRECIST Response Assessment 
Overall response will also be assessed using iRECIST.  Immunotherapeutics may result in 
infiltration of immune cells leading to transient increase in the size in malignant lesions, or 
undetectable lesions becoming detectable.  The criteria are identical to those of RECIST 1.1 
in many respects but have been adapted to account for instances where an increase in tumor 
burden, or the appearance of new lesions, does not reflect true tumor progression. 
Key differences are described below.  All responses defined using iRECIST criteria are 
designated with a prefix.  iRECIST time-point and best overall responses will be recorded 
separately. iRECIST criteria is applicable only after RECIST1.1 progression occurs. 
Confirming Progression 
Unlike RECIST 1.1, iRECIST requires the confirmation of progression and uses the terms 
iUPD (unconfirmed progression) and iCPD (confirmed progression).  Confirmatory scans 
should be performed at least 4 weeks, but no longer than 8 weeks after iUPD. 
iCPD is confirmed if further increase in tumor burden, compared to the last assessment, is 
seen as evidenced by one or more of the following: 
• 
Continued increase in tumor burden (from iUPD) where RECIST 1.1 definitions of 
progression had been met (from nadir) in target, non-target disease or new lesions 
o Progression in target disease worsens with an increase of at least 5 mm in the 
absolute value of the sum 
o Continued unequivocal progression in non-target disease with an increase in 
tumor burden 
o Increase in size of previously identified new lesion(s) (an increase of at least 5 mm in 
the absolute value of the sum of those considered to be target new lesions) or 
additional new lesions. 
• 
RECIST 1.1 criteria are met in lesions types (target or non-target or new lesions) where 
progression was not previously identified, including the appearance of additional new 
lesions. 


 
 
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If iUPD is not confirmed at the next assessment, then the appropriate response will be assigned 
(iUPD if the criteria are still met, but no worsening, or iSD, iPR or iCR if those criteria 
are met compared to baseline).  As can be seen in the table below, the prior documentation of 
iUPD does not preclude assigning iCR, iPR, or iSD in subsequent time-point assessments or as 
best overall response (BOR) providing that iCPD is not documented at the next assessment after 
iUPD. 
New Lesion 
New lesions should be assessed and measured as they appear using RECIST 1.1 criteria 
(maximum of 5 lesions, no more than 2 per site, at least 10 mm in long axis (or 15 mm in short 
axis for nodal lesions), and recorded as New Lesions-Target (NLT) and New Lesion-Non-Target 
(NLNT) to allow clear differentiation from baseline target and non-target lesions. 
New lesions may either meet the criteria of NLT or NLNT to drive iUPD (or iCPD). 
However, the measurements of target lesions should NOT be included in the sum of measures 
of original target lesions identified at baseline.  Rather, these measurements will be collected 
on a separate table in the case report form. 
PD is confirmed in the New Lesion category if the next imaging assessment, conducted at least 
4 weeks (but not more than 8 weeks) after iUPD confirms further progression from iUPD with 
either an increase of at least 5 mm in the absolute value of the sum of NLT OR an increase 
(but not necessarily unequivocal increase) in the size of NLNT lesions OR the appearance of 
additional new lesions. 
Time-Point (TP) Response 


 
 
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Target Lesions* 
Non-Target 
Lesions* 
New 
Lesions* 
Time Point Response 
No 
prior 
iUPD** 
Prior iUPD**; *** 
iCR 
iCR 
No 
iCR 
iCR 
iCR 
Non-iCR/Non- iUPD 
No 
iPR 
iPR 
iPR 
Non-iCR/Non- iUPD 
No 
iPR 
iPR 
iSD 
Non-iCR/Non- iUPD 
No 
iSD 
iSD 
iUPD with no 
change  
OR 
decrease from   last 
TP 
iUPD with no change  
OR decrease from last 
TP 
Yes 
NA 
NLs confirms iCPD if NLs were previously 
identified and increase in size (≥ 5 mm in 
SOM for NLT or any increase for NLNT) 
or number. If no change in NLs (size or 
number) from last TP, remains iUPD 
iSD 
iUPD 
No 
iUPD 
Remains iUPD unless iCPD confirmed based 
in further increase in size of NT disease (need 
not meet RECIST 1.1 criteria for unequivocal 
PD) 
iUPD 
Non-iCR/Non- iUPD 
No 
iUPD 
Remains iUPD unless iCPD confirmed based 
on: 
o further increase in SOM of at least 5 mm, 
otherwise remains iUPD 
iUPD 
iUPD 
No 
iUPD 
Remains iUPD unless iCPD confirmed based 
on further increase in: 
o previously identified T lesion iUPD SOM 
≥ 5 mm and / or 
o NT lesion iUPD (prior assessment - need 
not be unequivocal PD) 
iUPD 
iUPD 
Yes 
iUPD 
Remains iUPD unless iCPD confirmed based 
on further increase in: 
o previously identified T lesion iUPD ≥ 5 mm 
and / or 
o previously   identified   NT   lesion   
iUPD (need   not   be unequivocal) and /or 
o size or number of new lesions previously 
identified 
Non- iUPD/PD 
Non-iUPD/PD 
Yes 
iUPD 
Remains iUPD unless iCPD confirmed based 
on 
* Using RECIST 1.1 principles. If no PSPD occurs, RECIST 1.1 and iRECIST categories for CR, PR and SD 
would be the same. ** in any lesion category. *** previously identified in assessment immediately prior to this TP. 
 
All patients will have their iBOR from the start of study treatment until the end of treatment 
classified as outlined in the table below (iRECIST Best Overall Response (iBOR) Time-Point). 
 
 
 
 


 
 
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iRECIST Best Overall Response (iBOR) Time-Point 
TPR1 
TPR2 
TPR3 
TPR4 
TPR5 
iBOR 
iCR 
iCR, iPR, 
iUPD, NE 
iCR, iPR, iUPD, 
NE 
iUPD 
iCPD 
iCR 
iUPD 
iPR, iSD, NE iCR 
iCR, iPR, iSD, iUPD, 
NE 
iCR, iPR, iSD, iUPD, iCPD, 
NE 
iCR 
iUPD 
iPR 
iPR, iSD, iUPD, 
NE 
iPR, iSD, iUPD, NE, 
iCPD 
iPR, iSD, iUPD, NE, iCPD 
iPR 
iUPD 
iSD, NE 
PR 
iPR, iSD, iUPD, NE 
iPR, iSD, iUPD, iCPD, NE 
iPR 
iUPD 
iSD 
iSD, iUPD, NE 
iSD, iUPD, iCPD, NE 
iSD, iUPD, ICPD, NE 
iSD 
iUPD 
iCPD 
Anything 
Anything 
Anything 
iCPD 
iUPD 
iUPD 
iCPD 
Anything 
Anything 
iCPD 
iUPD 
NE 
NE 
NE 
NE 
iUPD 
Table assumes a randomized study where confirmation of CR or PR is not required. This study requires confirmation of CR or 
PR same duration with RECIST criteria. 
NE = not evaluable that cycle. 
Designation “I” for BOR can be used to indicate prior iUPD to aid in data interpretation. 
For patients with non-target disease only at baseline, only CR or non-CR/non-PD can be assigned at each TPR but is not 
shown in the table for ease of presentation. 
Response and Stable Disease Duration (RECIST 1.1 and iRECIST) 
Response duration will be measured from the time measurement criteria for CR/PR or iCR/iPR 
(whichever is first recorded) are first met until the first date that recurrent or progressive 
disease is objectively documented, taking as reference the smallest measurements recorded on 
study (including baseline). 
Stable disease duration will be measured from the time of start of treatment until the criteria for 
progression are met, taking as reference the smallest sum on study (including baseline) are met, 
taking as reference the smallest sum on study (including baseline). 
 
 


 
 
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APPENDIX 4. CA-125 GYNECOLOGIC CANCER INTER GROUP 
CRITERIA* 
Definition of CA-125 response  
A CA-125 response is defined as at least a 50% reduction in CA-125 levels from latest baseline 
sample from C1D1. In addition, those patients who have a CA-125 response and whose CA-125 
level falls to within the normal range can be classified as CA-125 complete responders. Patients 
can be evaluated according to CA-125 only if they have a baseline sample that is at least twice 
the upper limit of normal range within 28 days of C1D1. Patients who have an initial CA-125 
which was less than twice the upper limit of the normal range will be evaluated for CA-125 
progression only. 
Definition of CA-125 progression  
CA-125 progression is defined as the progressive serial elevation of serum CA-125, according to 
the following modified GCIG criteria: 
• 
Patients with elevated CA-125 pre-treatment, must show evidence of CA-125 greater 
than, or equal to, two times the nadir value in the 28-day period before C1D1on two 
occasions at least one week apart, 
• 
Patients with CA-125 in the normal range pre-treatment must show evidence of CA-125 
greater than, or equal to,  
Time to progression is determined by the first date of assessment which showed two times the 
ULN or nadir on two occasions at least one week apart. 
Summary Table of CA-125 Assessment* 
Response: 
Definition: 
Applies to:  
CA-125 complete 
response 
At least a 50% reduction in CA-125 
levels from baseline and whose CA-125 
level falls to within the normal range 
Those patients who have a baseline 
sample that is at least twice the 
upper limit of normal range within 
28 days of C1D1 
CA-125 partial 
response 
At least a 50% reduction in CA-125 
levels from baseline, but not within 
normal range 
Non-PR/non-PD 
Neither at least a 50% reduction in CA-
125 levels from baseline nor progression 
Not PD 
Not meet the criteria of progression (not 
evaluable population for CA-125 
response) 
Patients who have an initial CA-125 
which was less than twice the upper 
limit of the normal range 
Progression 
2-fold increase from the baseline CA-
125 (if above the ULN at 
All patients 


 
 
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baseline) or 2-fold greater than the ULN 
(if below the ULN at baseline)  
* Modified from original GCIG criteria for exploratory endpoint of this study 
 
 


 
 
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APPENDIX 5. GLUCOCORTICOID DOSE EQUIVALENTS  
Equivalent Dose 
Steroid 
1.2 mg 
Betamethasone (long acting) 
1.5 mg 
Dexamethasone (long acting) 
8 mg 
Methylprednisolone (intermediate-acting) 
8 mg 
Triamcinolone (intermediate-acting) 
10 mg 
Prednisone (intermediate-acting) 
10 mg 
Prednisolone (intermediate-acting) 
40 mg 
Hydrocortisone (short-acting) 
50 mg 
Cortisone (short-acting) 
Source:  http://emedicine.medscape.com/article/2172042-overview 
 
 
 


 
 
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APPENDIX 6. COMMON TERMINOLOGY CRITERIA FOR ADVERSE 
EVENTS  
The link below is for the Common Terminology Criteria for Adverse Events, Version 4.03 
(CTCAE, v4.03): 
https://www.eortc.be/services/doc/ctc/ctcae_4.03_2010-06-14_quickreference_5x7.pdf 
 
 
 


 
 
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APPENDIX 7. PHASE 2 STUDY DESIGN FLOW  
 
HLA eligible
Yes
No
Screening
eligible
HLA 
screening fail
Yes
No
Screening 
fail
DSP-7888 Q1W
DSP-7888 Q3W
Pembrolizumab Q3W
Discontinued due to 
reason other than PD
Follow up tumor 
assessment
Follow up Survival/New 
anticancer treatment  
Discontinued 
due to PD
Screening
Period
Treatment
Period
Follow up
Period
Induction Phase
Maintenance Phase
HLA Screening
Period


 
 
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APPENDIX 8. LEGACY PHASE 1 TREATMENT SCHEDULE 
Table 12: 
Legacy Phase 1* DSP-7888 Dosing Emulsion, Nivolumab, and 
Pembrolizumab Treatment Dose and Schedule 
DSP-7888 Dosing Emulsion 
Treatment Schedule 
DSP-7888 Dosing Emulsion, Nivolumab, 
Pembrolizumab 
Dose 
Level 
Dose 
Intensity 
Number of 
Injection* 
Sites 
Amount 
Per 
Injection* 
Site (mL) 
Total Amount 
to Administer 
Per Dosing 
Day (mL) 
Nivolumab Arm  
(Arm 1) 
Pembrolizumab Arm 
(Arm 2) of Phase 1b and 
Phase 2 
DSP-7888 
Dosing 
Emulsion 
Dose 
Level I 
10.5 mg  
 
 
6 
 
0.1 
 
0.6 
DSP-7888 Dosing 
Emulsion 
induction phase: 
weekly for 4 weeks  
then  
maintenance phase: 
every 2 weeks 
 
nivolumab 
240 mg  
administered IV  
over 30 (±5) minutes 
every  
14 days (2 weeks) 
 
DSP-7888 Dosing 
Emulsion 
induction phase: weekly 
for 6 weeks  
then  
maintenance phase: 
every 3 weeks 
 
pembrolizumab 
200 mg/8mL 
administered IV  
over 30 (±5) minutes  
every  
21 days (3 weeks) 
 
 
 
DSP-7888 
Dosing 
Emulsion 
Dose 
Level II 
3.5 mg  
 
 
2 
 
0.1 
 
0.2 
DSP-7888 
Dosing 
Emulsion 
Dose 
Level III 
(only used 
for dose 
reduction) 
1.75 mg  
 
 
1 
 
0.1 
 
0.1 
Abbreviations: IV – intravenous(ly) 
*Legacy schedule refers to that which was followed prior to Amendment 5. 


 
 
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Figure 5: 
Schematic of Legacy Study Conduct 
 

SAP_001.pdf: 




  
 
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Table of Contents 
AMENDMENTS FROM PREVIOUS VERSION(S) .....................................................................6 
LIST OF ABBREVIATIONS ..........................................................................................................7 
1. 
INTRODUCTION ......................................................................................................10 
1.1. 
Study Design ...............................................................................................................10 
1.2. 
Objectives and Endpoints ...........................................................................................10 
1.2.1. 
Phase 1b ......................................................................................................................10 
1.2.1.1. 
Primary Endpoints: .....................................................................................................12 
1.2.1.2. 
Secondary Endpoints: .................................................................................................13 
1.2.1.3. 
Exploratory Endpoints: ...............................................................................................18 
1.2.2. 
Phase 2 ........................................................................................................................20 
1.2.2.1. 
Primary Endpoint: .......................................................................................................22 
1.2.2.2. 
Secondary Endpoints: .................................................................................................23 
1.2.2.3. 
Exploratory Endpoints: ...............................................................................................23 
2. 
HYPOTHESES AND DECISION RULES ................................................................25 
2.1. 
Statistical Hypotheses .................................................................................................25 
2.2. 
Statistical Decision Rules ...........................................................................................25 
2.3. 
Sample Size Considerations and Power Calculation ..................................................25 
3. 
ANALYSIS POPULATIONS ....................................................................................26 
3.1. 
Full Analysis Set .........................................................................................................26 
3.2. 
Safety Set ....................................................................................................................26 
3.3. 
Treatment Allocation ..................................................................................................26 
4. 
DATA HANDLING CONVENTIONS ......................................................................27 
4.1. 
Data Presentation Conventions ...................................................................................27 
4.2. 
Baseline Definition .....................................................................................................27 
4.3. 
Derived and Transformed Data ..................................................................................27 
4.3.1. 
Baseline Age ...............................................................................................................27 
4.3.2. 
Study Day ...................................................................................................................27 
4.3.3. 
Duration: .....................................................................................................................27 
4.3.4. 
Change from Baseline .................................................................................................27 
4.4. 
Handling of Missing Data ...........................................................................................28 
4.4.1. 
Missing or Partial Death Dates ...................................................................................28 
4.4.2. 
Missing or Partial Dates in Adverse Events ...............................................................28 


  
 
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4.4.3. 
Missing or Partial Dates in Concomitant Medications ...............................................29 
4.4.4. 
Missing or Partial New Anti-Cancer Therapy Start Date ...........................................29 
5. 
STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES .................30 
5.1. 
General Statistical Methods ........................................................................................30 
5.1.1. 
Analysis for Continuous Data .....................................................................................30 
5.1.2. 
Analysis for Categorical Data .....................................................................................30 
5.2. 
Standard Analysis .......................................................................................................30 
5.2.1. 
Subjects Disposition ...................................................................................................30 
5.2.2. 
Demographic and Baseline Characteristics ................................................................30 
5.2.3. 
Disease Characteristics, Cancer History and Prior Cancer treatment .........................30 
5.2.4. 
Prior and Concomitant Medications ...........................................................................31 
5.2.5. 
Medical History ..........................................................................................................31 
5.2.6. 
Extent of Exposure .....................................................................................................31 
5.2.6.1. 
Exposure of DSP7888.................................................................................................34 
5.2.6.2. 
Exposure of Nivolumab ..............................................................................................35 
5.2.6.3. 
Exposure of Pembrolizumab .......................................................................................35 
5.3. 
Statistical Methodology ..............................................................................................36 
5.4. 
Safety Analyses ..........................................................................................................37 
5.4.1. 
Adverse Events ...........................................................................................................37 
5.4.2. 
Clinical Laboratory Evaluations .................................................................................39 
5.4.3. 
Electrocardiograms .....................................................................................................40 
5.4.4. 
Vital Signs ..................................................................................................................40 
5.5. 
Efficacy Analyses .......................................................................................................41 
5.6. 
Pharmacodynamic and Biomarker Analysis ...............................................................41 
REFERENCES ..............................................................................................................................42 
APPENDIX 1. RESPONSE EVALUATION CRITERIA IN SOLID TUMORS ......................43 
 
 
 
 




  
 
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LIST OF ABBREVIATIONS 
Abbreviation or  
specialist term 
Explanation 
ADI 
Actual Dose Intensity 
AE 
Adverse Event 
ALT 
Alanine Transaminase  
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body Mass Index 
BOR 
Best Overall Response 
CD8+ 
Cells containing Cellular Receptor, Cluster of Differentiation 
8 
CR 
Complete Response 
CS 
Clinically Significant 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTL 
Cytotoxic T Lymphocyte 
DCR 
Disease Control Rate 
DDS 
The Dose-Determining Set 
DLT 
Dose-limiting Toxicity 
DOR 
Duration of Response 
DSP 
Sumitomo Dainippon Pharma 
DSP-7888 
(Adegramotide/Nelatimotide 
[INN] and Ombipepimut-S 
[USAN]) 
code name for the dipeptide vaccine of DSP-7888-H and 
DSP 7888-K  
DSP-7888-H 
Helper Peptide 
DSP-7888-K 
Cytotoxic T lymphocyte-inducing (Killer) Peptide 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group (performance status) 
eCRF 
electronic Case Report Form 
EOT 
End of Treatment 
ES 
Efficacy Set 
FT4 
Free Thyroxine 4  
GBM 
Glioblastoma Multiforme 
GCIG 
Gynecological Cancer Intergroup 
HCC 
Hepatocellular carcinoma 
HEENT 
Head, Eyes, Ears, Nose, Throat  
HLA 
Human Leukocyte Antigen 
HNSCC 
Head and Neck Squamous Cell Carcinoma(s) 
HPV 
Human Papilloma Virus 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IHC 
Immunohistochemistry 
INN 
International Nonproprietary Name 
iRECIST 
immune-related Response Evaluation Criteria in Solid 
Tumors 


  
 
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Abbreviation or  
specialist term 
Explanation 
ISR 
Injection Site Reaction 
ITT 
Intent to Treat 
LVEF 
Left Ventricular Ejection Fraction 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHC 
Major Histocompatibility Complex 
MRI 
Magnetic Resonance Imaging 
MSKCC 
Memorial Sloan-Kettering Cancer Center 
MSI 
Microsatellite Instability 
MSI-H/dMMR 
Microsatellite instability-high or mismatch repair deficient 
MTD 
Maximum Tolerated Dose 
MUGA 
Multigated Acquisition Scan 
NCI 
National Cancer Institute 
NCS 
Not Clinically Significant 
NSCLC 
Non-Small Cell Lung Cancer 
ODI 
Overall Dose Intensity 
ORR 
Objective Response Rate 
OS 
Overall Survival 
PD 
Progressive Disease/Disease Progression 
PD-L1 
Programmed Death Ligand 1 
PD-1 
Programmed Cell Death Protein 1 
PET 
Positron Emission Tomography 
PFS 
Progression-free Survival 
PFSr 
Progression-free Survival Ratio 
PR 
Partial Response 
PROC 
Platinum-resistant Ovarian Cancer  
PT 
Preferred Term 
QTc 
corrected QT 
RCC 
Renal Cell Carcinoma 
RDI 
Relative Dose Intensity 
RECIST 
Response Evaluation Criteria in Solid Tumors 
ROC 
Receiver Operating Characteristic 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Stable Disease 
 
 
SI 
Standard International 
SOC 
System Organ Class 
SS 
Safety Set 
Std Dev 
Standard Deviation 
TAA 
Tumor-associated antigens 
TEAE 
Treatment-Emergent Adverse Event 
TIL 
Tumor Infiltrating Lymphocytes 
TLF 
Tables, Listings, and Figures 
TSH 
Thyroid-stimulating Hormone  
ULN 
Upper Limit of Normal 


  
 
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Abbreviation or  
specialist term 
Explanation 
WHO 
World Health Organization 
WT1 
Wilms’ Tumor 1 


  
 
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1. 
INTRODUCTION 
This statistical analysis plan (SAP) describes the statistical methods that will be used during the analysis 
and reporting of data collected under Sumitomo Pharma Oncology Protocol DSP7888-102CI. This SAP 
should be read in conjunction with the study protocol and electronic case report forms (eCRFs).  This 
version of the SAP has been developed using BBI-DSP7888-102CI_aCRF_21Jul2020 FINAL.pdf.   
1.1. 
Study Design 
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: Phase 1b (a dose search part and an enrichment part) and Phase 2 dose-expansion. In the Phase 1b 
part 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, a Phase 1b enrichment cohort of a further 10 patients, who have locally advanced or 
metastatic renal cell carcinoma (RCC) or urothelial cancer with primary or acquired resistance to 
previously administered checkpoint inhibitors, will be enrolled and will be dosed with DSP-7888 Dosing 
Emulsion and nivolumab, or DSP-7888 Dosing Emulsion and pembrolizumab, as per the investigator’s 
preference. The purpose of this Phase 1b enrichment cohort is to help evaluate the preliminary antitumor 
activity of DSP-7888 Dosing Emulsion at the safe dose level identified in the Phase 1b dose-search part.  
Once the recommended dose is determined in the Phase 1b dose search part, platinum-resistant ovarian 
cancer (PROC) patients will be enrolled in the Phase 2 part of the study and treated with DSP-7888 
Dosing Emulsion, exploring the combination with pembrolizumab. In Phase 2, a total of approximately 
40 patients with PROC will be enrolled. Additional patients may be enrolled to further assess anti-tumor 
activity in the subgroups of interest. However, the total sample size of Phase 2 part cannot exceed 60 
patients. 
1.2. 
Objectives and Endpoints 
1.2.1. 
Phase 1b  
A summary of objectives and endpoints of Phase 1b of the study is presented in  Table 1 below. 
Table 1: 
Objectives and Endpoints for Phase 1b.  
 
Objectives 
Endpoints 
 
Phase 1b  
Primary 
Objective 
To evaluate the safety and 
tolerability, and identify a 
recommended intradermal dose of 
DSP-7888 Dosing Emulsion in 
combination with nivolumab or 
pembrolizumab 
1. Incidence of DLTs, except for those 
patients treated in the enrichment cohort 
2. Incidence and severity of AEs, serious 
AEs (SAEs)  
3. Dose interruption, reduction, and dose 
intensity  
Secondary 
Objective 
To evaluate the preliminary 
antitumor activity of DSP-7888 
Dosing Emulsion in combination 
with nivolumab and pembrolizumab 
1. ORR, defined as proportion of patients 
who have achieved confirmed complete 
response (CR) or partial response (PR), 
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Objectives 
Endpoints 
 
in terms of ORR, disease control rate 
(DCR), duration of response (DOR), 
6-month progression-free survival 
(PFS) Rate, overall survival (OS) 
Criteria in Solid Tumors (RECIST) (v.1.1) 
and immune RECIST (iRECIST) based on 
investigator assessment 
2. DCR, defined as the percentage of 
patients who have achieved best 
overall response (BOR) of CR, PR, or 
stable disease (SD) per RECIST 
(v.1.1) and iRECIST 
3. DOR, defined as the time from the 
first documentation of a response (CR 
or PR) until time of first 
documentation of disease progression 
by RECIST (v.1.1) and iRECIST, or 
death by any cause 
4. PFS, defined as the time from the date 
of the first dose of study treatment to 
the earlier date of assessment of 
progression by RECIST (v.1.1) and 
iRECIST, or death by any cause  
5. 6-month PFS Rate, defined as the 
proportion of patients who neither 
progressed by RECIST (v.1.1) and 
iRECIST nor died before 6 months 
from the first study treatment 
6. OS, defined as the time from the date 
of the first dose of study treatment to 
the date of death by any cause 
Exploratory 
Objective 
To characterize pharmacodynamic 
(PD) or potential predictive 
biomarkers and their relationship to 
clinical activity 
Biomarkers using peripheral blood samples 
and tumor tissue samples in patients receiving 
DSP-7888 Dosing Emulsion in combination 
with pembrolizumab may be evaluated for 
correlation with the following immunologic 
changes and/or clinical responses 
1. WT1-specific CTL induction activity in 
blood samples 
2. WT1 expression level via chromogenic in 
situ hybridization (CISH) and PD-L1 
expression level via 
immunohistochemistry (IHC) 
3. CD8+ cell density in tumor tissues  
4. Tumor infiltrating lymphocytes (TILs) 
profiling in tumor tissues 
5. Immune profiling in tumor tissues with 
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Objectives 
Endpoints 
 
6. Mutation status and tumor mutation 
burden (TMB) in tumor tissues 
 
To determine the PFS ratio as an 
evaluation of treatment benefit of 
DSP-7888 Dosing Emulsion 
administered with nivolumab or 
pembrolizumab 
PFS ratio is defined as PFS/PFS (-1) ratio 
using RECIST (v.1.1)  
1. PFS is defined as the time from the date 
of the first dose of study treatment to the 
earlier date of assessment of progression 
by RECIST (v.1.1), or death by any cause 
2. PFS (-1) is defined as the date of initiation 
of the previous (penultimate) treatment 
regimen to the date of assessment of 
progression by RECIST (v.1.1) 
Abbreviations: AEs = adverse events; CTL = cytotoxic T lymphocyte; DCR = disease control rate; DOR = duration 
of response; IHC = immunohistochemistry; iRECIST = Immune Response Evaluation Criteria In Solid Tumors; 
ORR = objective response rate; OS = overall survival; PFS = progression-free survival; RECIST = Response 
Evaluation Criteria In Solid Tumors; SAEs = serious adverse events; TIL = tumor-infiltrating lymphocytes; 
TMB = tumor mutation burden; WT1 = Wilms Tumor 1 
*Note: It should be ensured that 8 to 23 slides of archival samples and/or the equivalent amount of archival tissue 
block and/or fresh biopsy samples from enrolled patients are available at Pre-screening/Screening. From patients 
who consent to providing additional samples by signing the additional informed consent for these optional samples, 
an additional 6 to 8 slides will be collected for future biomarker analysis. These samples must contain sufficient 
tumor tissue. Details of the biopsy time points are described in the schedule of assessments (SOA) in Protocol Table 
7 and Table 8.  
1.2.1.1. 
Primary Endpoints:  
Primary Endpoints include: Incidence of DLTs, except for those patients treated in the enrichment cohort, 
incidence and severity of AEs, serious AEs (SAEs), dose interruption, dose reduction, and dose intensity 
(Section 5.2.9 ).   
1.2.1.1.1. Dose-limiting Toxicities (Phase 1b Dose Search Part Only) 
A dose-limiting toxicity (DLT) is defined by the occurrence of 1 of the toxicities defined below, 
occurring during the first 28 days of Arm 1 (DSP-7888 Dosing Emulsion induction phase in combination 
with nivolumab; Arm 1) and the first 42 days of Arm 2 (DSP-7888 Dosing Emulsion induction phase in 
combination with pembrolizumab; Arm 2).  
The following treatment-related AEs will be considered a DLT: 
Non-hematologic 
• 
Any treatment-related Grade 3 or higher non-hematologic clinical (non-laboratory) AE, with 
the following exceptions: 
− 
Grade 3 nausea/vomiting or Grade 4 vomiting that resolves to Grade 1 or 2 in 72 hours or 
less with appropriate supportive care 
− 
Grade 3 or 4 diarrhea that resolves to Grade 1 or 2 in 72 hours or less with appropriate 
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− 
Grade 3 fatigue lasting <5 days 
− 
Grade 3 hypertension that can be controlled with medical therapy within 7 days 
• 
Any treatment-related Grade 3 or higher non-hematologic laboratory abnormality if: 
− 
Medical intervention is required to treat the patient, or 
− 
The abnormality leads to hospitalization, or 
− 
The abnormality persists for ≥7 days 
Hematologic 
• 
Any treatment-related hematologic toxicity specifically defined as:  
− 
Thrombocytopenia Grade 4 or higher, or Grade 3 associated with bleeding  
− 
Neutropenia Grade 4 for ≥7 days, or Grade 3 or 4 associated with infection or febrile 
neutropenia  
− 
Anemia Grade 4, or Grade 3 or 4 requiring blood transfusion 
Immune-related 
• 
Grade 3 or higher CTCAE v. 4.03 immune system disorder-related adverse reactions that 
persist as Grade 3 for >14 days, despite appropriate treatment, except for allergic reactions 
and autoimmune reaction 
• 
Any Grade 3 or higher allergic reaction 
• 
Any Grade 2 or higher autoimmune reaction with the following exceptions:  
− 
Grade 2 elevation of transaminases/hepatitis that recovers to Grade 0 or 1 within 10 days 
(for patients with liver metastases, elevation of transaminases due to hepatitis that 
recovers to baseline within 10 days) 
− 
Grade 2 hypothyroidism that recovers to Grade 0 or 1 within 7 days without steroids 
− 
Grade 2 diarrhea/colitis that spontaneously recovers to Grade 0 or 1 within 7 days with 
supportive care but without steroids 
− 
Grade 2 immune-related rash/dermatitis 
• 
Any treatment-related Grade 4 ISR or Grade 3 ISR that requires hospitalization. 
1.2.1.2. 
Secondary Endpoints: 
Objective disease assessments will be performed according to RECIST (v1.1) and iRECIST, with the first 
assessment performed at the end of the dose-limiting toxicity (DLT) period (Cycle 3: at 4 weeks for 
nivolumab arm, at 6 weeks for pembrolizumab arm), and at Weeks 12, 18, and 24 after the first dose of 
DSP-7888 Dosing Emulsion. After that, objective disease assessments will occur every 12 weeks until 
disease progression.  


  
 
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1.2.1.2.1. Best Overall Reponses, Objective Response Rate and Disease Control Rate, and 
Duration of Response per RECIST (v1.1) 
Objective disease assessments will be performed according to RECIST (v1.1) and iRECIST, with the first 
assessment performed at the end of the dose-limiting toxicity (DLT) period (Cycle 3: at 4 weeks for 
nivolumab arm, at 6 weeks for pembrolizumab arm), and at Weeks 12, 18, and 24 after the first dose of 
DSP-7888 Dosing Emulsion. After that, objective disease assessments will occur every 12 weeks until 
disease progression. 
Best Overall Response (BOR) per RECIST (v1.1) is the best response recorded from first dose 
until disease progression or start of new anti-cancer therapy. Tumor scan assessment done after PD 
or after “new anti-cancer” treatment will not be considered in the evaluation of BOR. BOR is derived 
from the sequence of objective response determined by the following order:  
• 
CR: One objective status of CR documented and confirmed (at least 4 weeks after) before 
progression or start of new anti-cancer therapy  
• 
PR: One objective status of PR documented and confirmed (at least 4 weeks after) before 
progression or start of new anti-cancer therapy, but not qualifying as CR  
• 
SD: At least 1 objective status of SD or better documented at least 1 nominal scan interval (6 
weeks – 2 days window = 40 days) after first dose date and before progression and the start of 
new anti-cancer therapy, but not qualifying as CR or PR  
• 
PD: Progression documented within 2 nominal scan intervals (or 12 weeks + 2 days window = 
86) after first dose date and not qualifying as CR, PR, or SD  
• 
NE: All other cases will be categorized as NE.  
Objective Response Rate (ORR) per RECIST (v.1.1) is defined as the proportion of patients who 
have achieved confirmed complete response (CR) or partial response (PR), evaluated using RECIST 
(v.1.1) by investigator assessment.  
The patients will be considered as non-responders until proven otherwise. Thus, the patients who:  
• Do not have CR or PR while on study; or  
• Do not have a baseline or post-baseline tumor evaluation; or  
• Do not have an adequate baseline tumor evaluation; or  
• Receive new anti-cancer treatment other than the study medication prior to reaching a CR or PR; or  
• Die, progress, or drop out for any reason prior to reaching a CR or PR  
are considered non-responders. 
Disease Control Rate (DCR) per RECIST (v.1.1) is defined as the percentage of patients with BOR of a 
documented complete response, partial response, and stable disease (CR + PR + SD), based on RECIST 
1.1, by investigator assessment. 
Duration of Response (DOR) per RECIST (v.1.1) is defined as the time from the first documentation of 
a response (CR or PR) until time of first documentation of disease progression by RECIST (v.1.1), or 
death by any cause.   
1.2.1.2.2. Best Overall Reponses, Objective Response Rate, Disease Control Rate and 
Duration of Response per iRECIST  
Best Overall Response per iRECIST (iBOR) is the best response recorded from first dose until 
confirmed progression of disease (iCPD) or start of new anti-cancer therapy. In accordance with 
iRECIST, patients with stable disease (iSD) or better after an initial unconfirmed progression of disease 
(iUPD) are evaluated after iUPD for iCR (complete response )/iPR (partial response)/iSD(stable disease) 
in the determination of iBOR.  Tumor scan assessment done after iCPD or after “new anti-cancer” 


  
 
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treatment will not be considered in the evaluation of iBOR. iBOR is derived from the sequence of 
objective response determined by the following order:  
• 
iCR: One objective status of iCR documented before iCPD or start of new anti-cancer therapy  
• 
iPR: One objective status of PR documented before iCPD or start of new anti-cancer therapy, but 
not qualifying as iCR  
• 
iSD: At least 1 objective status of iSD or better documented within at least 1 nominal scan 
interval (6 weeks – 2 days window = 40 days) after first dose date or from previous adequate 
tumor assessment and before iCPD and the start of new anti-cancer therapy, but not qualifying as 
iCR or iPR  
• 
iUPD (unconfirmed progression of disease): iUPD documented after first dose date and not 
qualifying as iCR, iPR, or iSD  
• 
iCPD (confirmed progression of disease): iCPD documented and not qualifying as iCR, iPR, or 
iSD or iUPD 
• 
NE: All other cases will be categorized as NE.  
Objective Response Rate per iRECIST (immune ORR, iORR) is defined as the proportion of 
patients who have achieved confirmed immune complete response (iCR) or immune partial response 
(iPR), evaluated using iRECIST by investigator assessment.  
The patients will be considered as non-responders until proven otherwise. Thus, the patients who:  
• Do not have iCR or iPR while on study; or  
• Do not have a baseline or post-baseline tumor evaluation; or  
• Do not have an adequate baseline tumor evaluation; or  
• Receive new anti-cancer treatment other than the study medication prior to reaching a iCR or iPR; 
or  
• Die, progress, or drop out for any reason prior to reaching a iCR or iPR  
are considered non-responders. 
Disease Control Rate per iRECIST (immune DCR, iDCR) is defined as the percentage of patients with 
iBOR of a documented complete response, partial response, and stable disease (iCR + iPR + iSD), based 
on iRECIST, by investigator assessment. 
Duration of Response per iRECIST (immune DOR, iDOR) is defined as the time from the first 
documentation of a response (iCR or iPR) until time of first documentation of disease progression by 
iRECIST or death by any cause.  Patients with iUPD at their last assessment were assigned a date of 
progression at the earliest timepoint iUPD was consecutively determined for that patient (ie, sequential 
iUPD determinations without an intervening iSD, iPR, or iCR determination). 
1.2.1.2.3. Progression Free Survival and 6 month PFS rate per RECIST (v1.1) 
Progression-Free Survival (PFS) per RECIST (v1.1) is defined as the time from the date of the first 
dose of study treatment to the first objective documentation of disease progression by RECIST (v.1.1) or 
death by any cause, whichever comes first. If a patient has not progressed or died at the time of analysis 
(up to the date of data cutoff), PFS will be censored on the date of the last tumor assessment (up to the 
date of data cutoff).  
PFS in months is calculated as (first event date/censored date – date of first dose +1)/30.4375. 
Table 2 summarizes the censoring rules for the PFS analysis. 


  
 
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Table 2: 
PFS Definition: Events and Censoring Reasons and Hierarchy 
Notes: (1) Symptomatic deteriorations (i.e. symptomatic progressions, which are not radiographically confirmed) will not be considered as 
progressions. 
(2) If target, non-target, and new lesion assessments have different dates within a visit, then the earliest of those dates will be considered as the 
date of the tumor assessment if the assessment for that visit is progressive disease (PD); otherwise the latest date will be used. 
(3) Adequate radiographical tumor assessment refers to an assessment with overall response of CR, PR, SD, non-CR/non-PD, or PD. 
Two scan intervals are 88 days (12 weeks+ 4 days) if previous assessment is within 124 days (18 weeks – 
2 days) from the first dose date; or 130 days (18 weeks + 4 days) if previous assessment is after 124 days 
but prior to 146 (24 weeks – 2 day) days from the first dose date, or 172 days (24 weeks + 4 days) if 
previous assessment is after 146 days from the first dose date.   
The 6-month PFS Rate per RECIST (v1.1) is defined as the proportion of patients who neither 
progressed by RECIST (v.1.1) nor died before 6 months from the first study treatment.   
Hierarchy 
Censoring 
Situation 
Date of Event or Censor 
Event / 
Censor 
1 
No baseline radiological tumor assessment 
available 
Date of first dose  
Censor 
5 
No post baseline radiological tumor 
assessment available and no death reported 
within 2 scan intervals following the first 
dose date.  
Date of first dose 
Censor 
 
No post baseline radiological tumor 
assessment available 
but death reported within 2 scan intervals 
following the first dose date 
Date of death 
Event 
6 
No tumor progression (per RECIST 1.1) 
and no death reported within 2 scan 
intervals following last adequate 
radiological tumor assessment 
Date of last adequate 
radiological 
tumor assessment  
Censor 
 
No tumor progression (per RECIST 1.1) 
but death reported within 2 scan intervals 
following last adequate radiological tumor 
assessment  
Date of death 
Event 
 
Tumor progression (per RECIST 1.1) 
documented within 2 scan intervals 
following previous adequate radiological 
tumor assessment 
Earliest of the target, non-
target and new tumor 
assessment dates 
Event 
3 
Tumor progression (per RECIST 1.1) 
documented after 2 scan intervals following 
previous adequate radiological tumor 
assessment 
Date of previous adequate 
radiological assessment 
Censor 
2 
New anticancer treatment started and no 
tumor progression 
Date of previous adequate 
radiological assessment 
immediately prior to start 
of new therapy 
Censor 
4 
No tumor progression (per RECIST 1.1) 
and patient lost to follow-up or withdrawal 
of consent 
Date of last adequate 
radiological 
Assessment 
Censor 


  
 
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1.2.1.2.4. Progression Free Survival and 6 month PFS rate per iRECIST 
Immune Progression-Free Survival (iPFS) is defined as the time from the date of the first dose of study 
treatment to the first objective documentation of disease progression by iRECIST or death by any cause, 
whichever comes first. If a patient has not progressed or died at the time of analysis (up to the date of data 
cutoff), iPFS will be censored on the date of the last tumor assessment (up to the date of data cutoff).   
The event date to be used for calculation of iPFS should be the first date at which progression criteria are 
met (ie, the date of immune unconfirmed progressive disease [iUPD]) provided that immune confirmed 
progressive disease [iCPD] is confirmed at the next assessment. If iUPD occurs, but is disregarded 
because of later iSD, iPR, or iCR, that iUPD date should not be used as the progression event date. 
Patients with iUPD at their last assessment were assigned a date of progression at the earliest timepoint 
iUPD was consecutively determined for that patient (ie, sequential iUPD determinations without an 
intervening iSD, iPR, or iCR determination).  
iPFS in months is calculated as (first event date/censored date – date of first dose +1)/30.4375. 
As patients who remain on study treatment following objective disease progression per RECIST (v.1.1) 
will continue to be evaluated for objective response to study treatment according to the SOA and to 
iRECIST, the censoring rules for iPFS is defined different from PFS.   
Table 3 summarizes the censoring rules for the iPFS analysis. 
Table 3: 
iPFS Definition: Events and Censoring Reasons and Hierarchy 
Hierarchy 
Censoring 
Situation 
Date of Event or Censor 
Event / 
Censor 
1 
No baseline radiological tumor assessment 
available 
Date of first dose  
Censor 
5 
No post baseline radiological tumor 
assessment available and no death reported 
within 2 scan intervals following the first 
dose date 
Date of first dose 
Censor 
 
No post baseline radiological tumor 
assessment available 
but death reported within 2 scan intervals 
following the first dose date 
Date of death 
Event 
6 
No tumor progression (iUPD/iCPD) per 
iRECIST and no death reported within 2 scan 
intervals following last adequate radiological 
tumor assessment 
Date of last adequate 
radiological 
tumor assessment  
Censor 
 
No tumor progression (iUPD/iCPD)  per 
iRECIST but death reported within 2 scan 
intervals following last adequate radiological 
tumor assessment  
Date of death 
Event 
 
Tumor progression (iCPD per iRECIST) 
documented.   
Date of iCPD  
Event 
 
Tumor progression (iUPD at their last 
assessment but sequential iUPD 
determinations without an intervening iSD, 
iPR, or iCR determination) 
Date of the earliest iUPD 
date.   
Event 


  
 
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Notes:  
(1) If target, non-target, and new lesion assessments have different dates within a visit, then the earliest of those 
dates will be considered as the date of the tumor assessment if the assessment for that visit is progressive disease 
(iUPD or iCPD); otherwise the latest date will be used. 
(2) Adequate radiographical tumor assessment refers to an assessment with overall response of iCR, iPR, iSD, 
iUPD, iCPD.  
Two scan intervals are same as defined for PFS derivation.   
The 6-month iPFS Rate per iRECIST is defined as the proportion of patients who neither progressed by 
iRECIST nor died before 6 months from the first study treatment.   
1.2.1.2.5. 
Overall Survival 
Overall Survival (OS) is defined as the time from the date of the first dose of study treatment to the date 
of death by any cause.  Patients who are still alive at the time of the analysis data cutoff date, or who have 
become lost to follow-up will be censored at their last date known to be alive on or before the date of data 
cutoff.  
OS in months is calculated as (date of death/last known to be alive – date of the first dose +1)/30.4375. 
Patients lacking any dates which support patients still alive beyond the first dose date will have their OS 
censored at the date of the first dose.   
1.2.1.3. 
Exploratory Endpoints:   
1.2.1.3.1. Pharmacodynamic (PD) and Biomarker Endpoints  
Biomarkers using peripheral blood samples and tumor tissue samples in patients receiving DSP-7888 
Dosing Emulsion in combination with pembrolizumab or nivolumab may be evaluated for correlation 
with the following immunologic changes and/or clinical responses. The endpoints includes:  
1.2.1.3.1.1. WT1-specific CTL induction activity in blood samples 
WT1 specific CTL induction activity will be measured every 2 cycles pre-dosing until dosing is 
discontinued (eg, Cycle 7, 9, 11, 13) for phase 1b, and at screening and, during treatment, prior to each 
dose Cycle 5, 7, 9 and subsequent assessments every 4 Cycle (Cycle 13, 17, 21 etc.) for phase 2 part.   
Depending on the HLA types, WT1 -specific CTL Induction will be measured differently.   
Hierarchy 
Censoring 
Situation 
Date of Event or Censor 
Event / 
Censor 
3 
Tumor progression (iUPD per iRECIST) 
but didn’t confirmed later or intervening of 
iSD, iPR or iCR  
Date of last adequate 
radiological assessment. 
Censor 
2 
New anticancer treatment started and no 
tumor progression (iCPD or iUPD) 
Date of previous adequate 
radiological assessment 
immediately prior to start 
of new therapy 
Censor 
4 
No tumor progression (iUPD/iCPD) and 
patient lost to follow-up or withdrawal of 
consent 
Date of last adequate 
radiological 
Assessment 
Censor 


  
 
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For patients with HLA-A*02:01 NOT HLA-A*02:06, below measurements will be measured and 
analyzed:  
• 
%WT137-45 Tet+ in CD8+ (P7/P6),  
• 
CD8+WT137-45 Tet+ (P7) Event #,  
For patients with HLA-A*02:01/HLA-A*02:06, below measurements will be measured and analyzed:  
• 
%WT137-45 Tet+ in CD8+ (P7/P6),  
• 
%WT1126-134 Tet+ in CD8+ (P8/P6),  
• 
CD8+WT137-45 Tet+ (P7) Event #,  
• 
CD8+WT1126-135 Tet+ (P8) Event # 
For patients with HLA-A*24:02, below measurements will be measured and analyzed: 
• 
%WT1235-243 Tet+ in CD8+ (P9/P6),  
• 
CD8+WT1235-243 Tet+ (P9) Event # 
For patients with HLA-A*03:01 or HLA-B*15:01, below measurements will be measured and analyzed: 
• 
%WT1126-134 Tet+ in CD8+,   
• 
CD8+WT1126-134 Tet+ Event# 
HLA-A*03:01 or HLA-B*15:01 will only be available for phase 2 not in phase 1b.   
 
 


  
 
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1.2.1.3.1.2. Other PD and Biomarker Endpoints 
• 
WT1 expression level via chromogenic in situ hybridization (CISH) and PD-L1 expression level 
via immunohistochemistry (IHC) 
WT1 expression level via chromogenic in situ hybridization (CISH) includes % Tumor cells WT1 
positive; and WT1 Tumor H-score 
• 
CD8+ cell density in tumor tissues  
• 
Tumor infiltrating lymphocytes (TILs) profiling in tumor tissues 
• 
Immune profiling in tumor tissues with tumor inflammation signature analysis   
• 
Mutation status and tumor mutation burden (TMB) in tumor tissues 
1.2.1.3.2. Progression Free Survival Ratio 
PFS (-1) is defined as the date of initiation of the previous (penultimate) treatment regimen to the date of 
assessment of progression by RECIST (v.1.1).   
PFS ratio is defined as PFS/PFS (-1) ratio using RECIST (v.1.1).   
1.2.2. 
Phase 2  
A summary of objectives, endpoints, and assessments of Phase II of the study is presented in 
Table 7 below. 
Table 4: 
Summary of Objectives and Endpoints for Phase 2 
 
Objectives  
Endpoints 
 
Phase 2 
Primary 
To evaluate the preliminary antitumor 
activity of DSP-7888 Dosing 
Emulsion administered with 
pembrolizumab in terms of ORR in 
patients with platinum-resistant 
ovarian cancer (PROC) 
ORR, defined as the proportion of patients 
who have achieved confirmed CR or PR, 
evaluated using RECIST (v.1.1) based on 
investigator assessment 
Secondary 
To evaluate the preliminary clinical 
activity of DSP-7888 Dosing 
Emulsion in combination with 
pembrolizumab in terms of DOR, 
DCR, PFS, 6 months PFS Rate, and 
OS of DSP-7888 Dosing Emulsion 
administered in combination with 
pembrolizumab in PROC 
1. 
DOR, defined as the time from the first 
documentation of a response (CR or PR) 
until time of first documentation of 
disease progression by RECIST (v.1.1), 
or death by any cause 
2. 
DCR, defined as the percentage of 
patients who have achieved BOR of CR, 
PR, or SD per RECIST (v.1.1)   
3. 
PFS, defined as the time from the date of 
the first dose of study treatment to the 
earlier date of assessment of progression 


  
 
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Objectives  
Endpoints 
 
by RECIST (v.1.1), or death by any 
cause  
4. 
6 months PFS Rate, defined as the 
proportion of patients who neither 
progressed by RECIST (v.1.1) nor died 
before 6 months (24 weeks) from the 
first study treatment 
5. 
OS, defined as the time from the date of 
the first dose of study treatment to the 
date of death by any cause 
To determine ORR, DCR, PFS, and 
iDOR per iRECIST of DSP-7888 
Dosing Emulsion administered in 
combination with pembrolizumab in 
PROC 
1. immune ORR (iORR), defined as 
proportion of patients who have achieved 
confirmed immune complete response 
(iCR) or immune partial response (iPR), 
evaluated using iRECIST based on 
investigator assessment  
2. immune DCR (iDCR), defined as the 
percentage of patients who have achieved 
BOR of iCR, iPR, or iSD per iRECIST 
3. immune PFS (iPFS), 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 
4. immune DOR (iDOR), defined as the time 
from the first documentation of response 
(iCR or iPR) until time of first 
documentation of disease progression by 
iRECIST, or death by any cause 
* The event date to be used for calculation of 
PFS should be the first date at which 
progression criteria are met (ie, the date of 
immune unconfirmed progressive disease 
[iUPD]) provided that immune confirmed 
progressive disease [iCPD] is confirmed at the 
next assessment. If iUPD occurs, but is 
disregarded because of later iSD, iPR, or iCR, 
that iUPD date should not be used as the 
progression event date 
To evaluate the safety and tolerability 
of DSP-7888 Dosing Emulsion 
administered with pembrolizumab 
Frequency and intensity of AEs using 
Common Terminology Criteria for Adverse 
Events (CTCAE) v 4.03 
Exploratory To determine the PFS rate as an 
evaluation of treatment benefit of 
PFS rate is defined as PFS1/PFS (-1) ratio 
using RECIST (v.1.1)  


  
 
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Objectives  
Endpoints 
 
DSP-7888 Dosing Emulsion 
administered with pembrolizumab 
1. PFS1 is defined as the time from the date 
of the first dose of study treatment to the 
earlier date of assessment of progression 
by RECIST (v.1.1), or death by any cause 
2. PFS (-1) is defined as the date of initiation 
of the previous (penultimate) treatment 
regimen to the date of assessment of 
progression by RECIST (v.1.1) 
To evaluate the antitumor activity of 
DSP-7888 Dosing Emulsion 
administered with pembrolizumab in 
terms of the CA-125 response rate 
and time to progression with CA-125 
criteria in PROC 
1. CA-125 response rate is defined as 
proportion of patients who have achieved 
response using the Gynecologic Cancer 
InterGroup (GCIG) CA-125 response 
definition 
2. Time to progression with CA-125 is 
defined as the time from the date of the 
first dose of study treatment to the earlier 
date of assessment of progression by 
GCIG CA-125 progression definition or 
death by any cause 
To characterize PD or potential 
predictive biomarkers and their 
relationship to clinical activity 
Biomarkers using peripheral blood samples 
and tumor tissue samples in patients receiving 
DSP-7888 Dosing Emulsion in combination 
with pembrolizumab may be evaluated for 
correlation with the following immunologic 
changes and/or clinical responses 
1. WT1-specific CTL induction activity in 
blood samples  
2. WT1 expression level via CISH and PD-
L1 expression status (CPS) via IHC in 
tumor tissue 
3. CD8+ cell density in tumor tissues  
4. TILs profiling in tumor tissues  
5. Immune profiling in tumor tissues with 
tumor inflammation signature analysis   
6. Mutation status and mutational burden 
analysis in tumor tissues  
7. HLA typing 
*Note: These samples must contain sufficient tumor tissue. Details of the biopsy time points are described in the 
SOA in Protocol Amendment 6 Table 9.   
1.2.2.1. 
Primary Endpoint:  
Primary Endpoint of phase 2 part is ORR per RECIST (v.1.1) based on investigator assessment (refer to 
Section 1.2.1.2.1 for the definition.) 


  
 
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1.2.2.2. 
Secondary Endpoints:  
Secondary endpoints include DOR, DCR, PFS, 6 – month PFS rate per RECIST (v1.1) (refer to for 
Section 1.2.1.2.1 Section 1.2.1.2.3 for definitions. ) ; iORR, iDCR , iDOR and iPFS per iRECIST based 
on investigator assessment (refer to Section 1.2.1.2.2 Section 1.2.1.2.4 for definition ) ; and OS (refer to 
Section 1.2.1.2.5 for definition ).   
Safety assessment of frequency and intensity of AEs assessed according to CTCAE v4.03. also included a 
secondary endpoint.   
1.2.2.3. 
Exploratory Endpoints:  
1.2.2.3.1. Progression Free Survival Ratio 
PFS (-1) is defined as the date of initiation of the previous (penultimate) treatment regimen to the date of 
assessment of progression by RECIST (v1.1).  PFS ratio is defined as PFS/PFS (-1) ratio using RECIST 
(v.1.1).   
1.2.2.3.2. CA-125 and Time to progression with CA-125 
For Phase 2, the CA-125 Response and time to CA-125 progression will be analyzed as exploratory 
endpoints using FAS as exploratory endpoints.  
CA-125 response rate is defined as proportion of patients who have achieved response using the 
Gynecologic Cancer InterGroup (GCIG) CA-125 response definition. (see Appendix 1 ) . A CA-125 
response is defined as at least a 50% reduction in CA-125 levels from latest baseline sample from C1D1. 
In addition, those patients who have a CA-125 response and whose CA-125 level falls to within the 
normal range can be classified as CA-125 complete responders. Patients can be evaluated according to 
CA-125 only if they have a baseline sample that is at least twice the upper limit of normal (ULN) range 
within 28 days of C1D1. Patients who have an initial CA-125 that was less than twice the ULN range will 
be evaluated for CA-125 progression only.  
Time to progression with CA-125 is defined as the time from the date of first dose of study treatment to 
the earlier date of assessment of progression by GCIG CA-125 progression definition or death by any 
cause. (See Appendix 1)  CA-125 progression is defined as the progressive serial elevation of serum CA-
125, according to the following modified Gynecologic Cancer Inter-Group (GCIG) criteria (Appendix 1 
) 
• 
Patients with elevated CA-125 pretreatment must show evidence of CA-125 greater than or equal 
to 2 times the nadir value in the 28-day period before C1D1 on 2 occasions at least 1 week apart, 
• 
Patients with CA-125 in the normal range pretreatment must show evidence of CA-125 greater 
than, or equal to, the ULN. 
Table 9: 
Summary of CA-125 Assessment 
Response: 
Definition: 
Applies to: 
CA-125 complete 
response 
At least a 50% reduction in CA-125 
levels from baseline and whose CA-
125 level falls to within the normal 
range 
Those patients who have a 
baseline sample that is at least 
twice the ULN range in CA-125 
partial 28 days of C1D1 
CA-125 partial response 
At least a 50% reduction in CA-125 
levels from baseline, but not within 
normal range 


  
 
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Non-PR/non-PD 
Neither at least a 50% reduction in 
CA-125 levels from baseline nor 
progression 
Not PD 
Not meeting the criteria of 
progression (not evaluable population 
for CA-125 response) 
Patients who have an initial CA-
125 that was less than twice the 
ULN range 
Progression 
2-fold increase from the baseline CA-
125 (if above the ULN at baseline) or 
2-fold greater than the ULN (if below 
the ULN at baseline) 
All patients 
ULN = upper limit of normal 
Time to progression is determined by the first date of the assessment that showed 2 times the ULN or 
nadir on 2 occasions at least 1 week apart, and will be calculated as: 
Time to CA-125 Progression (months) = (Date of Progression / censor – Date of first dose + 1) / 30.4375. 
Patients last known to be progression-free are censored at the date of the last overall assessment that 
verified lack of CA-125 progression (either scheduled or unscheduled visit). 
1.2.2.3.3. Pharmacodynamic (PD) and Biomarker Endpoints  
Biomarkers using peripheral blood samples and tumor tissue samples in patients receiving DSP-7888 
Dosing Emulsion in combination with pembrolizumab may be evaluated for correlation with the 
following immunologic changes and/or clinical responses 
• 
WT1-specific CTL induction activity in blood samples (refer to Section 1.2.1.3.1.1 ) 
• 
WT1 expression level via CISH and PD-L1 expression status (CPS) via IHC in tumor tissue 
• 
CD8+ cell density in tumor tissues  
• 
TILs profiling in tumor tissues  
• 
Immune profiling in tumor tissues with tumor inflammation signature analysis   
• Mutation status and mutational burden analysis in tumor tissues  
• 
HLA typing: potential include: HLA-A*02:01, HLA-A*02:06, HLA-A*24:02, HLA-A*03:01 and 
HLA-B*15:01.  


  
 
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2. 
HYPOTHESES AND DECISION RULES 
2.1. 
Statistical Hypotheses 
There is no formal hypothesis for this study including phase 1b and phase 2 part.   
2.2. 
Statistical Decision Rules 
For Phase 2 Cohort Only 
There is no formal hypothesis testing for the Phase 2 cohort. A Bayesian decision-making framework will 
be employed to quantify whether proof of concept (POC) can be established based on the overall response 
rate (ORR) by Week 24 from the final analysis for the overall population and/or the CPS 
< 10 subpopulation. The POC is established at the final analysis if either or both of the following 
2 conditions are met:  
• 
In the overall population, 70% credible interval of ORR with 10% in the left tail and 20% in 
the right tail will be calculated: if lower bound ≥ 8% and upper bound ≥ 21% (where 8% is 
the reference value [Protocol Amend 6, Section 4.3.1; Matulonis, 2019] and 21% is the target 
value of ORR in the overall population), the study will achieve POC. 
• 
In the CPS< 10 subpopulation, 50% credible interval of ORR with 20% in the left tail and 
30% in the right tail will be calculated: if lower bound ≥ 5% and upper bound ≥ 15% (where 
5% is the reference value [Protocol Amend 6, Section 4.3.1; Matulonis, 2019] fand 15% is 
the target value of ORR in CPS < 10 subpopulation), the study will achieve POC.  
The interim monitoring analysis for futility early efficacy assessment will be conducted using a Bayesian 
method and will start after the first 20 patients have response evaluation, withdraw, or die by Week 24.  
• 
If the posterior probability of ORR ≥ 21% in the overall population is ≤ 2.5% AND the posterior 
probability of ORR ≥ 15% in the CPS < 10 subpopulation is ≤ 2.5%, the study is futile and 
further enrollment will be stopped. 
• 
If the posterior probability of ORR ≥ 21% in overall population is ≥ 80% AND the posterior 
probability of ORR ≥ 15% in CPS < 10 subpopulation is ≥ 70%, then early success is met and 
further enrollment may be stopped.   
• 
Otherwise, the enrollment will continue as is until 40 patients.  
The above decision rules for interim analysis are non-binding.  
2.3. 
Sample Size Considerations and Power Calculation 
In Phase 1b of the study, there will be approximately 6 to 12 patients for each arm, up to a total of 
24 patients. As part of these 24 patients, an enrichment cohort of 10 patients will be enrolled into Phase 
1b. If anti-tumor activities are observed in any tumor type, additional patients may be enrolled for further 
assessment.  
In Phase 2 of the study, approximately 20 to 40 patients will be enrolled. Additional patients may be 
enrolled to further assess anti-tumor activities in the subgroups of interest. However, the total sample size 
of Phase 2 cannot exceed 60 patients. In total, approximately 64-84 patients will be enrolled in the study. 


  
 
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3. 
ANALYSIS POPULATIONS 
3.1. 
Full Analysis Set 
The Full Analysis Set (FAS) consists of all patients who receive at least 1 full or partial dose of study 
treatment (DSP-7888 Dosing Emulsion, nivolumab, or pembrolizumab). Patients will be classified 
according to the treatment assigned (dose level and schedule). 
3.2. 
Safety Set 
The Safety Set (SS) consists of all patients who receive at least 1 full or partial dose of study treatment 
(DSP-7888 Dosing Emulsion, nivolumab, or pembrolizumab). Patients will be classified according to the 
treatment received (dose level and schedule), where treatment received is defined as the actual treatment 
if the patients took at least 1 dose of that treatment or the first treatment received if the assigned treatment 
was never received. 
Safety analysis set will be used for all safety related analyses such as AE, concomitant medication, 
laboratory tests, and vital signs and drug exposure evaluation.   
3.3. 
Treatment Allocation  
Phase 1b (a dose search part and an enrichment part) of this study, there will be 2 arms: Arm 1 and Arm 
2:  
• 
Arm 1: DSP-7888 Dosing Emulsion + nivolumab combination: 
• 
Arm 2: DSP-7888 + pembrolizumab combination: 
Phase 1b patients who get at least one dose of DSP-7888 and nivolumab will belong to Arm 1; and who at 
least one dose of DSP-7888 and pembrolizumab will belong to Arm 2.   
Phase 2 part of the study, patients will be treated with DSP-7888 Dosing Emulsion in combination with 
pembrolizumab.   
 


  
 
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4. 
DATA HANDLING CONVENTIONS 
4.1. 
Data Presentation Conventions 
Means and medians will be presented to 1 more decimal place than the recorded data. The standard 
deviations (SDs) will be presented to 2 more decimal places than the recorded data. Confidence intervals 
about a parameter estimate will be presented using the same number of decimal places as the parameter 
estimate. 
4.2. 
Baseline Definition 
Baseline is defined as the most recent, non-missing value prior to or on the first study drug dose date 
within 28 days from first dose.   
4.3. 
Derived and Transformed Data 
4.3.1. 
Baseline Age 
The reference date for age is the date of Screening informed consent. Age is calculated as the (reference 
date – date of birth +1)/365.25 round down to the nearest integer. 
4.3.2. 
Study Day 
Study day 1 is defined as the treatment start date. Study day is calculated as: 
• 
Date of interest – treatment start date + 1, if the assessment was performed on or after the 
treatment start date; 
• 
Date of interest – treatment start date, if the assessment was performed prior to the treatment 
start date. 
There is no safety study Day 0. 
4.3.3. 
Duration:  
• 
Duration in days: (End Date – Start Date + 1) 
• 
Duration in weeks: (End Date – Start Date + 1) / 7 
• 
Duration in months: (End Date – Start Date + 1) / 30.4375; Average days in months = average 
number of days in a year /12 
• 
Duration in years: (End Date – Start Date + 1) / 365.25; Average days in a year = 365.25, 
reflecting the Julian Year of 3 years with 365 days each and 1 leap year of 366 days. 
4.3.4. 
Change from Baseline 
Change from baseline is calculated as (visit value – baseline value).  
Percent change from baseline is calculated as (change from baseline/baseline value) x 100 when baseline 
value is not 0. 
Post / pre ratio is calculated as Visit value / baseline value when baseline value is not 0.   
If either the baseline value or visit value is missing, the change from baseline and/or percent change from 
baseline is set to missing as well. 


  
 
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Schedule and unscheduled visits post baseline: unless otherwise specified, for the summary by visit post 
baseline, only scheduled visits will be included; for summary of the maximum or maximum changes post 
baseline, all scheduled visits and unscheduled visits will be included. All records (scheduled/unscheduled) 
regardless post baseline reporting period or not will be listed in the data listings.  
4.4. 
Handling of Missing Data 
For the patient data listings, no imputation of incomplete dates will be applied. The listings will present 
the incomplete dates without any change. 
4.4.1. 
Missing or Partial Death Dates 
When the death is missing or is partial, it will be imputed based on the last contact date.  
• 
If the entire date is missing, the death date will be imputed as the day after the date of last contact. 
• 
If the day or both day and month is missing, the death date will be imputed to the maximum date 
among the following dates:  
1 day after the date of last contact;   
1st day of the month and year of death, if day of death is missing OR 
January 1st of the year of death, if both the day and month of death are missing. 
4.4.2. 
Missing or Partial Dates in Adverse Events 
Every effort will be made to avoid missing/partial adverse event dates in on-study data. 
Adverse events with start date that is completely or partially missing will be imputed as follows: 
• 
If the start date has month and year but day is missing, the first day of the month will be imputed; 
o If this date is earlier than the first dose date, then the first dose date will be used instead; 
o If this date is later than the stop date (possibly imputed), then the stop date will be used 
instead. 
• 
If the start date has year, but day and month are missing, the 15th of June will be imputed: 
o If this date is earlier than the first dose date, then the first dose date will be used instead; 
o If this date is later than the stop date (possibly imputed), then the stop date will be used 
instead. 
If the start date of an event is completely missing, then it is imputed with the first dose date.  
Adverse events with stop dates that are completely or partially missing will be imputed as follows:  
• 
If the stop date has month and year but day is missing, the last day of the month will be imputed;  
• 
If the stop date has year, but day and month are missing,  the 31th of December will be imputed. 
After the imputation, the imputed dates will be compared against the date of death, if available. If the date 
is later than the date of death, the date of death will be used as the imputed date instead. 


  
 
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4.4.3. 
Missing or Partial Dates in Concomitant Medications 
Every effort will be made to avoid missing/partial concomitant medication dates in on-study data. 
Concomitant medication with start dates that are completely or partially missing will be analyzed as 
follows to be included as Concomitant Medications summary tables : 
• 
If the start date has month and year but day is missing, the medication will be included in the 
summary table if the month and year of the start date of the event are:  
o On or after the month and year of the date of the first dose of study drug and  
o On or before the month and year of the date of the last dose of study drug plus 30 days. 
• 
If the start date has year, but day and month are missing, the therapy will be included in the 
summary table if the year of the start date of the event is: 
o On or after the year of the date of the first dose of study drug and  
o On or before the year of the date of the last dose of study drug plus 30 days. 
If the start date of an event is completely missing, then the therapy will be included in the summary table.  
4.4.4. 
Missing or Partial New Anti-Cancer Therapy Start Date 
Post treatment anti-cancer therapy and radiotherapy start dates may be imputed to determine date of new 
anti-cancer therapy.  
Incomplete dates for start date of new anti-cancer therapy will be imputed as follows and will be used for 
determining censoring dates for efficacy analyses.   
• 
The end date of new anti-cancer therapy will be included in the imputations for start date of new 
anti-cancer therapy.  If the end date of new anti-cancer therapy is 
o completely missing then it will be ignored in the imputations below; 
o partially missing with only year (YYYY) available then the imputations below will 
consider 31DECYYYY as the end date of the new anti-cancer therapy; 
o partially missing with only month and year available then the imputations below will 
consider the last day of the month for MMMYYYY as the end date of the new anti-
cancer therapy. 
• 
For patients who have not discontinued study drug at the analysis cutoff date, last dose of study 
drug is set to the analysis cutoff date is the imputations below  
• 
If the start date of new anti-cancer therapy is completely or partially missing, the imputed start 
date of new anti-cancer therapy is: 
= 31DECYYYY, if only Year is available and Year < Year of min [max(PD date + 1, last dose of 
study drug + 1), end date of new anti-cancer therapy]  
= Last day of the month, if both Year and Month are available and  
Year = Year of min [max(PD date + 1, last dose of study drug + 1), end date of new anti-
cancer therapy]  
Month < Month of min [max(PD date + 1 day, last dose of study drug + 1 day), end date 
of new anti-cancer therapy] 
= min [max(PD date + 1, last dose of study drug + 1), end date of new anti-cancer therapy], for 
all other cases.  


  
 
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5. 
STATISTICAL METHODOLOGY AND STATISTICAL 
ANALYSES 
As the study was terminated for phase 2 portion due to the interim monitoring for efficacy.  The final 
CSR will focus on the safety updates for the study as a synoptic CSR.  As a result, the analyses strategy 
will focus on the safety portion.  No analysis for efficacy and PD/biomarker are included for the final 
CSR.   
Whilst every effort has been made to pre-specify all analyses in this statistical analysis plan, if any 
additional exploratory analyses be found to be necessary, the analyses and the reasons for them will be 
detailed in the clinical study report (CSR).  
5.1. 
General Statistical Methods 
5.1.1. 
Analysis for Continuous Data 
Descriptive statistics, including the mean, standard deviation, median, minimum and maximum values 
will be provided for continuous endpoints. 
5.1.2. 
Analysis for Categorical Data 
The number and percentage of patients in each category will be provided for categorical variables. 
Change from baseline for Categorical data will be evaluated by shift table if appropriate.  
5.2. 
Standard Analysis 
5.2.1. 
Subjects Disposition 
All patients who signed pre-screened and screened informed consent will be summarized.  The number 
and percentage of study patients will be tabulated for different analysis sets (Section 3 ) and by different 
phases and treatment information below.   
Phase 1b:  Arm 1, Arm 2; Overall,  
Phase 2:  CPS < 10, CPS >= 10, Overall  
The number and percentage of patients reaching end of treatment, and end of study, along with the 
discontinuation reasons will be summarized as treatment assignment in phase 1b and CPS subgroups and 
overall in phase 2.   
Listing for analysis sets and end of treatment and end of study reasons will be provided.   
5.2.2. 
Demographic and Baseline Characteristics 
The following demographic and baseline characteristics will be summarized.  
• 
Age, Age group (< 65 years and >= 65 years), sex, race, ethnicity, ECOG status, and smoking 
history, HLA type, CPS score, and CA-125 (for phase 2 only).   
• 
Weight (kg), height (cm), body mass index (BMI).   
Demographic and baseline characteristics will also be listed for each patient. 
5.2.3. 
Disease Characteristics, Cancer History and Prior Cancer treatment  
Disease characteristics including, but not limited to, cancer type, cancer history, prior cancer therapy, 
baseline tumor burden will be summarized:   


  
 
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• 
Cancer type 
• 
Duration of Last Cancer Therapy in weeks: calculated by (end date - start date + 1) / 7 from last 
cancer therapy, Status of patient entering study in regarding to the last therapy.   
• 
Number of prior therapy (1,2, >=3).   
• 
Prior Bevacizumab (only for phase 2 part):  
• 
Prior cancer system medication (Yes vs No); the number and percentage of patients with each 
preferred base, best response from prior cancer system medication will be summarized. If 
multiple best responses are reported, the best one is reported. 
• 
Prior Radiotherapy: prior radiotherapy (Yes, No),  time (months) since Stop Date of Radiation 
Therapy to the first dose date(Computed as [(first dose date) – (stop date of radiation therapy) + 
1]/30.4375), Number of Fractions and Total Dose (Gy) per person, best response from prior 
cancer radiotherapy will be summarized. If multiple best responses are reported, the best one is 
reported.  
• 
Prior Cancer Surgery (Yes , No) and by SOC and Preferred Terms of Medical Dictionary for 
Regulatory Activities (MedDRA 20.0).   
• 
Tumor Burden: Sum of Product of Diameters of Target Lesion (mm2), Site of Target Lesion 
5.2.4. 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded to ATC (Anatomical Therapeutic Chemical) 
classification and Drug Name using WHODrug Dictionary (WHO-DD-B2) version June 2017. 
Medications that start and stop prior to the date of first treatment administration (either DSP-7888 or 
checkpoint inhibitor (CPI) whichever is administrated first) will be classified as ‘prior’ medications. If a 
medication starts on or after the date of first treatment administration, then the medication will be 
classified as ‘concomitant’. If a medication starts before the date of first treatment administration and 
stops on or after the date of first treatment administration, then the medication will be categorized as both 
a ‘prior’ and ‘concomitant’ medication. 
Prior and concomintant medications will be listed for the safety analysis set.  
5.2.5. 
Medical History 
Medical history will be coded using MedDRA v20.0.  Medical history will be listed.   
5.2.6. 
Extent of Exposure 
Dose Schedule for phase 1b part is summarized as below:   


  
 
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Table 5: 
Phase 1b Study Dose Level and Schedule 
DSP-7888 Dosing Emulsion Dose 
Level 
 
DSP-7888 Dosing Emulsion Dose and Schedule 
DSP-7888 Dosing Emulsion Dose 
Level I 
Nivolumab Arm (Arm 1): 10.5 mg weekly for 4 weeks for induction phase, 
then every 2 weeks for maintenance phase  
Pembrolizumab Arm (Arm 2): 10.5 mg weekly for 3 weeks for induction 
phase, then every 3 weeks for maintenance phase  
DSP-7888 Dosing Emulsion Dose 
Level II 
Nivolumab Arm (Arm 1): 3.5 mg weekly for 4 weeks for induction phase, 
then every 2 weeks for maintenance phase 
Pembrolizumab Arm (Arm 2): 3.5 mg weekly for 3 weeks for induction 
phase, then every 3 weeks for maintenance phase  
DSP-7888 Dosing Emulsion Dose 
Level III 
Nivolumab Arm (Arm 1): 1.75 mg weekly for 4 weeks for induction 
phase, then every 2 weeks for maintenance phase  
Pembrolizumab Arm (Arm 2): 1.75 mg weekly for 3 weeks for induction 
phase, then every 3 weeks for maintenance phase 
 
Table 6: 
PD-1 Inhibitor Dose 
PD1 Inhibitor 
Dose and Schedule 
Nivolumab  
In Arm 1, 240 mg administered intravenously (IV) over 30 minutes 
(±5)* every 14 days (2 weeks/cycle) starting from Day 1 of Cycle 3 
(Day 29), then maintenance phase (after Cycle 3). 
Pembrolizumab 
In Arm 2, 200 mg/8 mL administered through IV infusion over 30 
(±5) minutes every 21 days (3 weeks) starting from Day 1 of Cycle 
2 (Day 22), then maintenance phase (after Cycle 2).  
*The administration time change from 60 to 30 minutes is based on the updated dosage and 
administration guidance of the new nivolumab product label released in July 2018.   
DSP-7888 Dosing Emulsion and pembrolizumab will be administered at the recommended dose level 
from the Phase 1 part of the study, following the same schedule as listed in Table 10.   
Table 7: 
Phase 2 Study Dosing Schedule  
Investigational 
Product 
Frequency 
Dosage  
Route of 
Administration 
DSP-7888 Dosing Emulsion 
Q1W for first 3 weeks 
Q3W post 3 weeks 
10.5mg 
Intradermal injection 
(ID) 
Pembrolizumab 
Q3W, starting from 
Day 1 of Cycle 2 
(Day 22) 
Solution for infusion 
200mg/8mL 
IV infusion  
The dose schedules for the study have been changed under different protocol amendment.  Below is a 
summary of the different dosing schedule:  


  
 
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Table 8: 
Planned Dose Intensity 
Treatment Group 
Dose Level 
During 
Induction Phase 
During 
Maintenance Phase 
DSP-7888 Dosing Emulsion + 
nivolumab 
Level I (10.5 mg) 
10.5 mg / week 
5.25 mg / week 
 
Level II (3.5 mg) 
3.5 mg / week 
1.75 mg / week 
 
Level III (1.75 mg) 
1.75 mg / week 
0.875 mg / week 
DSP-7888 Dosing Emulsion + 
pembrolizumab 
Level I (10.5 mg) 
10.5 mg / week 
3.5 mg / week 
 
Level II (3.5 mg) 
3.5 mg / week 
1.17 mg / week 
 
Level III (1.75 mg) 
1.75 mg / week 
0.58 mg / week 
In Phase 2, the dose of DSP-7888 Dosing Emulsion will be the recommended dose, as determined in the 
Phase 1b Arm 2 part (DSP-7888 + pembrolizumab) of the study  
 
 
 




  
 
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• 
Intended Treatment Duration (weeks) in the induction phase = (first dose date of DSP7888 in 
the maintenance phase - first dose date of DSP7888 in the induction phase )/7 or ( last dose 
date of DSP7888 in the induction phase - first dose date of DSP7888 in the induction phase + 
7) /7 if patients didn’t enter the maintenance phase   
• 
Actual Cumulative Dose (mg) in the induction phase = Sum of all administered doses of 
DSP7888 (mg) in the induction phase 
• 
Actual Dose Intensity (mg/week), ADI in the induction phase = Actual Cumulative Dose 
(mg) / Intended Treatment Duration (weeks) in the induction phase 
• 
Relative Dose Intensity (%), RDI in the induction phase = 100* ADI (mg/week) / Planned 
Dose Intensity (Table 11 ) 
For the maintenance phase:  
• 
Intended Treatment Duration (weeks) in the maintenance phase = (last dose date of DSP7888 in 
the maintenance phase - first dose date of DSP7888 in the maintenance phase + intended timing) 
/7. Intended timing is 14 days in combination with nivolumab   and 21 days in combination with 
pembrolizumab.  
• 
Actual Cumulative Dose (mg) in the maintenance phase = Sum of all administered doses of 
DSP7888 (mg) in the maintenance phase 
• 
Actual Dose Intensity (mg/week), ADI in the maintenance phase = Actual Cumulative Dose (mg) 
/Intended Treatment Duration (weeks) in the maintenance phase 
• 
Relative Dose Intensity (%), RDI in the maintenance phase = 100* ADI (mg/week) / Planned 
Dose Intensity (Table 11 ) 
5.2.6.2. 
Exposure of Nivolumab 
Nivolumab is planned to provide as 240 mg administered intravenously (IV) over 30 minutes (±5)* every 
14 days (2 weeks/cycle).  The exposure of nivolumab   is summarized as below:   
• 
Intended Treatment Duration (weeks) = (last dose date of nivolumab   – first dose date of nivolumab   
+ 14 days)/7.   
• 
Actual Cumulative Dose (mg) = Sum of all administered dose of nivolumab   
• 
Actual Dose Intensity (mg/week), ADI = Actual Cumulative Dose (mg) / Intended Treatment 
Duration (weeks) 
• 
Relative Dose Intensity (%), RDI = 100 * ADI (mg/week) / (120 mg / week) 
5.2.6.3. 
Exposure of Pembrolizumab  
Pembrolizumab is provided as 200 mg/8 mL administered through IV infusion over 30 (±5) minutes 
every 21 days. The exposure of pembrolizumab is summarized as below:   
• 
Intended Treatment Duration (weeks) = (last dose date of pembrolizumab – first dose date of  
pembrolizumab   + 21 days)/7.   
• 
Actual Cumulative Dose (mg) = Sum of all administered dose of pembrolizumab 


  
 
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• 
Actual Dose Intensity (mg/week), ADI = Actual Cumulative Dose (mg) / Intended Treatment 
Duration (weeks) 
• 
Relative Dose Intensity (%), RDI = 100 * ADI (mg/week) / (200 / 3 (mg / week) ) 
5.3. 
Statistical Methodology 
Phase 1b  
Determination of Recommended Dose of DSP-7888 Dosing Emulsion with nivolumab or pembrolizumab 
(Only Phase 1b) 
Determination of a recommended dose of DSP-7888 Dosing Emulsion in combination with nivolumab or 
pembrolizumab will be based on the criteria defined herein. 
Initially, 6 patients will be enrolled into each of the Arms according to a rolling 6 study design at the 
DSP-7888 Dosing Emulsion Dose Level I of 10.5 mg weekly, in combination with either nivolumab 240 
mg (every 2 weeks; Arm 1) or pembrolizumab 200 mg (every 3 weeks; Arm 2).   
The recommended dose of DSP-7888 Dosing Emulsion in combination with a given PD-1 inhibitor agent 
will be determined in each study Arm. Dose adjustments will proceed independently in each study Arm.  
The recommended dose of DSP-7888 Dosing Emulsion must be less than or equal to a dose level at 
which 1 out of 6 patients enrolled experience a DLT (see definition of a DLT in Section 7.4 of protocol). 
A dose level is eligible for consideration as the recommended dose if 0 or 1 of 6 patients enrolled 
experience a DLT at that dose level.   
Criteria for determining whether a given dose level is eligible to be considered a recommended dose of 
DSP-7888 Dosing Emulsion are based on the number of patients with DLTs out of the total number of 
DLT-eligible patients in a given cohort.  The criteria are as specified below: 
• 
If 0 or 1 out of 6 patients at the starting dose level experience a DLT, then the dose level is 
eligible for consideration as the recommended dose of DSP-7888. 
• 
If 2 or more out of 6 patients at a given dose level experience a DLT, then the dose will be 
decreased.  Further enrollment will be made at the lower dose level.  If 0 or 1 out of 6 patients 
at the lower dose level experience a DLT, then the dose level is eligible for consideration as the 
recommended dose of DSP-7888. 
The determination of the recommended dose of DSP-7888 Dosing Emulsion in a given study Arm also 
will be based on overall tolerability, including a review of persistent Grade 2 AEs and a review of AEs 
occurring beyond the first 2 dosing cycles.   
Phase 2 
A Bayesian decision making framework will be employed to quantify whether proof of concept (POC) 
can be established based on the overall response rate (ORR) by Week 24 from the final analysis for the 
overall population and/or the CPS < 10 subpopulation. The POC is established at the final analysis if 
either or both of the following 2 conditions are met:  
• 
In the overall population, 70% credible interval of ORR with 10% in the left tail and 20% in the right 
tail will be calculated: if lower bound ≥ 8% and upper bound ≥ 21% (where 8% is the reference value 
[Section 4.3.1] and 21% is the target value of ORR in the overall population), the study will achieve POC. 
• 
In the CPS< 10 subpopulation, 50% credible interval of ORR with 20% in the left tail and 30% in the 
right tail will be calculated: if lower bound ≥ 5% and upper bound ≥ 15% (where 5% is the reference 


  
 
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value [Section 4.3.1] and 15% is the target value of ORR in CPS < 10 subpopulation), the study will 
achieve POC.  
The interim monitoring analysis for futility or early efficacy assessment will be conducted using a 
Bayesian method and will start after the first 20 patients have response evaluation, withdraw, or die by 
Week 24.  
• 
If the posterior probability of ORR ≥ 21% in the overall population is ≤ 2.5% AND the posterior 
probability of ORR ≥ 15% in the CPS < 10 subpopulation is ≤ 2.5%, the study is futile and further 
enrollment will be stopped. 
• 
If the posterior probability of ORR ≥ 21% in overall population is ≥ 80% AND the posterior 
probability of ORR ≥ 15% in CPS < 10 subpopulation is ≥ 70%, then early success is met and further 
enrollment may be stopped.   
• 
Otherwise, the enrollment will continue until 40 evaluable patients have been accrued.  
The above decision rules for interim analysis are non-binding.  
5.4. 
Safety Analyses 
The safety and tolerability of DSP-7888 Dosing Emulsion in combination with immunotherapy PD-1 
inhibitors will be assessed for the duration of study treatment until 30 days after last dose date.   
5.4.1. 
Adverse Events 
Treatment-Emergent Adverse Events 
An AE will be regarded as treatment-emergent, if 
• 
it occurs for the first time on or after the first dose date of either DSP-7888 or CPI up to 30 days 
after the last dose of study drug; or 
• 
it occurs up to any time if serious and considered related to study drug. 
The emphasis for AE analysis will be based on treatment-emergent AE (TEAE), however all AEs will be 
listed.  
All AEs will be coded using Medical Dictionary for Regulatory Activities (MedDRA version 20.0) and 
summarized by MedDRA System Organ Class and Preferred Term. The severity of all AEs will be graded 
by the Investigator using NCI CTCAE version 4.0. 
An overview of treatment-emergent adverse events (TEAEs) will be provided.  The number and 
percentage of subjects with following will be summarized for phase 1b, Arm 1 and Arm2 overall, phase 
2: CPS < 10, CPS > = 10 and Overall.   
• 
Subjects with any TEAE  
• 
Subjects with TEAE of CTCAE grade 3 or higher 
• 
Subjects with serious adverse events (all causality and related) 
• 
TEAEs related to study drug 
• 
TEAEs related to study drug with CTCAE grade 3 or higher 
• 
Subjects with TEAE leading to study drug discontinuation (all causality and related) 
• 
Subjects with TEAE leading to study drug dose reduction(all causality and related) 
• 
Subjects with TEAE leading to study drug dose interruption  (all causality and related) 
 


  
 
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Summary of AEs by SOC and Preferred Term 
The number and percentage of subjects with TEAEs by SOC, PT and maximum CTCAE grade will be 
summarized. A summary of TEAEs of CTCAE grade 3 or higher (Grade 3, 4, 5) will be presented by 
SOC and PT and maximum CTCAE grade (All Grade, ≥Grade 3).  
The number and percentage of patients who experience any TEAE will be summarized by SOC and PT 
(All Grade, ≥Grade 3). A summary of TEAEs by PT and maximum CTCAE grade will be presented. The 
most commonly reported TEAEs using a different cutoff (e.g. 2% or 10% or more of patients in either 
arm) may also be summarized by PT as needed.  
TEAEs associated with permanent discontinuation /dose reduction/drug interruption of either DSP7888 
and/or CPI will be summarized by SOC and PT and maximum CTCAE Grade (taking into consideration 
the action taken from CRF AE page). 
Treatment Related Adverse Events 
Treatment-related TEAEs are those judged by the investigator to be at least possibly related to the study 
drugs (DSP7888 and/or CPI) or for which relatedness is recorded as “unknown” by the investigator. 
Treatment related will include “possible”, “probable” or “definite” causality assessments. Missing 
relationship will be considered as “Related” to all drugs received by the patient. Similar summaries as 
noted for all causality TEAEs will be provided for treatment related TEAEs. 
Serious Adverse Events and Death 
Treatment-emergent SAEs and Treatment-related SAEs will be summarized by MedDRA SOC and PT 
and maximum CTCAE grade. 
TEAE leading to death will be summarized by MedDRA SOC and Preferred Term. 
Deaths will be summarized by on study and on treatment (within 30 days of last dose of study 
medication). The number and percentage of patients who died on study and on treatment, as well as 
primary cause of death will be summarized. Deaths may also be categorized according to time of 
occurrence after first dose. 
A listing of death data will also be provided and will include all deaths that occurred from the signing of 
the informed consent to the end of the follow up period. The listing will include primary cause of death 
and the number of days relative to the administration of first and last dose. 
Adverse Events of COVID-19 
Preferred Terms corona virus infection and coronavirus test positive will be used to identified COVID-19 
positive cases in adverse event. 
Injection Site Reaction (ISR) 
The predominant adverse effect observed with DSP-7888 is injection site reaction. The Preferred Terms 
of TEAEs within the High Level Group Term of “Administration Site Reaction” (MedDRA version 20.0) 
will be used to identify events of injection site reaction.  
Below analysis will be provided for ISR: 
• 
ISR by SOC, PT, and maximum CTCAE Grade 
• 
Onset time of first ISR for patients with at least one ISR: Time to onset is analyzed for patients with 
at least one ISR from the first dose of the DSP-7888 to the first occurrence of ISR regardless of CTCAE 
grade. 
• 
Onset time of first ISR: Time to first ISR is defined as the time from the first dose of the DSP-7888 to 
the first occurrence of ISR . For patients with no ISR, the onset time will be censored as data cutoff date, 


  
 
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end of study date, death date, or safety follow-up completion date (end of treatment date + 30 days) 
whichever is shorter. 
• 
Onset time of the first Grade 3 or higher ISR for patients with at least one Grade 3 or higher ISR: 
Time to onset is analyzed for patients with at least one Grade 3 or higher ISR from the first dose of DSP-
7888 to the first occurrence of the Grade 3 or higher ISR. 
• 
Onset time of the first Grade 3 or higher ISR: Time to first Grade 3 or higher ISR is defined as the 
time from the first dose of DSP-7888 to the first occurrence of the Grade 3 or higher ISR. For patients 
with no Grade 3 or higher ISR, the onset time will be censored as data cutoff date, end of study date, 
death date, or safety follow-up completion date (end of treatment date + 30 days) whichever is shorter. 
• 
Duration of ISR and Duration of Grade 3 or higher ISR and may be analyzed in the CSR.  The 
duration is defined as (end date – start date + 1), and for ongoing ISR/ or ongoing Grade 3 or higher ISR, 
the ISR end date is truncated as the minimum of {by data cutoff date, end of study date, death date, last 
known to be alive date, or safety follow-up completion date (end of treatment date + 30 days)} whichever 
is shorter. 
A listing of ISR will also be provided. 
5.4.2. 
Clinical Laboratory Evaluations 
All samples will be analyzed at a central laboratory and collected per Schedule of Assessments in the 
protocol. Local laboratories may be used as deemed necessary by the Investigator in order to make 
treatment related decisions. 
The results of laboratory parameters will be graded according to NCI CTCAE v4.03 for below parameters 
(Table 12 ).  For patients with both baseline and post baseline assessments, a summary of shift from 
baseline CTCAE grade to maximum postbaseline CTCAE grade will be provided. All records on or after 
the first dose (scheduled and unscheduled) until 30 days following the last dose of study drug will be 
considered as post baseline. Additional parameters may be added for the shift tables. Both scheduled and 
unscheduled laboratory test results will be included in the shift tables.  
For the purposes of summarization in both the tables and listings, all laboratory values will be converted 
to standardized units.  If a lab value is reported using a non-numeric qualifier (e.g., less than (<) a certain 
value, or greater than (>) a certain value), the given numeric value will be used in the summary statistics, 
ignoring the non-numeric qualifier. 
Table 9:      CTCAE Lab Grading Parameters.  
↓ 
↑ 
HEMATOLOGY Anemia 
 
HEMATOLOGY White blood cell decreased 
 
HEMATOLOGY Lymphocyte count decreased  
HEMATOLOGY Neutrophil count decreased 
 
HEMATOLOGY Platelet count decreased 
 
CHEMISTRY 
  
Alanine aminotransferase increased 


  
 
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CHEMISTRY 
Hypoalbuminemia 
  
CHEMISTRY 
  
Alkaline phosphatase increased 
CHEMISTRY 
  
Aspartate aminotransferase increased 
CHEMISTRY 
  
Blood bilirubin increased 
CHEMISTRY 
  
Blood Urea Nitrogen Increased  
CHEMISTRY 
Hypocalcemia 
Hypercalcemia 
CHEMISTRY 
  
Creatinine increased 
CHEMISTRY 
Hypoglycemia 
Hyperglycemia 
CHEMISTRY 
Hypomagnesemia  
Hypermagnesemia  
CHEMISTRY 
Hypophosphatemia 
  
CHEMISTRY 
Hypokalemia 
Hyperkalemia 
CHEMISTRY 
Hyponatremia 
Hypernatremia 
Blood Urea Nitrogen Increased is not in CTCAE grading, SDPO will define as grade 1 is 23 – 26 mg/dL, 
grade 2 is 27-31 mg/dL, grade 3, >31 mg/dL. 
Listings of hematology and biochemistry, urinalysis and coagulation will be provided, including the test 
result, units, normal range, change from baseline, and CTCAE grade if available.  
5.4.3. 
Electrocardiograms 
A 12-lead Electrocardiogram (ECG) with categorical results (normal; abnormal, not clinically significant; 
abnormal, clinically significant) will be summarized in the shift summary from baseline to worst post 
baseline. Post baseline includes non-missing records collected (scheduled and unscheduled) after the first 
dose of study treatment until 30 days following the last dose of study treatment. QT measurements 
corrected by heart rate will be used for the data analysis and interpretation. QTc interval will be calculated 
using Fridericia’s correction. The formula is: 
Fridericia’s correction: QTcF = QT ∕RR0.33 
where unit of QT is milliseconds (msec) and unit of RR is second (sec). The number and percentage of 
patients in QT and QTcF (QT and QTcF interval: ≤ 450 msec, > 450 - ≤ 480 msec, > 480 - ≤ 500 msec, 
and > 500 msec) will be summarized at baseline and maximum post baseline. Categories of maximum 
changes from baseline (≤ 30 msec, > 30 - ≤ 60 msec, > 60 msec) will be summarized as well. 
An ECG result listing that including PR interval, RR interval, QT, QTc, QRS duration and Heart Rate 
will also be provided. 
5.4.4. 
Vital Signs 
Body temperature will be summarized in °C. If body temperature is recorded as °F, then temperature will 
be converted to °C using: 


  
 
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Temperature (°C) = 5/9 (Temperature [°F]-32).  
Summaries of post baseline markedly abnormal vital signs, including systolic blood pressure, diastolic 
blood pressure, pulse rate, weight change, and temperature will be presented. Markedly abnormal ranges 
for vital signs parameters are given in Table 13 . Post baseline includes non-missing records from both 
scheduled and unscheduled visits after the first dose of study drug until 30 days following the last dose of 
study treatment. 
Table 10: 
Markedly Abnormal Ranges for Vital Signs 
Parameter 
Markedly Abnormal (Low) 
Markedly Abnormal (High) 
Systolic Blood 
Pressure 
• 
Absolute value ≤ 90 mmHg for 
post baseline, or  
• 
a decrease from baseline ≥20 
mmHg for change from baseline 
• 
Absolute value ≥ 180 mmHg for 
post baseline, or  
• 
an increase from baseline ≥20 
mmHg for change from baseline 
Diastolic Blood 
Pressure 
• 
Absolute value ≤ 50 mmHg for 
post baseline, or   
• 
a decrease from baseline ≥15 
mmHg for change from baseline 
• 
Absolute value ≥ 105 mmHg for 
post baseline, or  
• 
an increase from baseline ≥ 15 
mmHg for change from baseline 
Pulse 
• 
Absolute value ≤ 50 bpm for post 
baseline, or   
• 
a decrease from baseline ≥ 15 
bpm for change from baseline 
• 
Absolute value ≥ 120 bpm for 
post baseline, or   
• 
an increase from baseline ≥ 
15bpm for change from baseline 
Weight Change 
Weight loss from baseline ≥ 20%  
Weight gain from baseline ≥ 20% 
Temperature 
≤ 35°C post baseline only 
≥ 40°C post baseline only 
A listing of vital signs results will also be presented using the Safety Set.  
5.5. 
Efficacy Analyses 
As the study was terminated for phase 2 portion due to the interim monitoring for efficacy.  The 
final CSR will focus on the safety updates for the study as a synoptic CSR.  As a result, there 
will no analysis included for efficacy portion.  The timepoint overall response evaluation, BOR, 
ORR, DCR and DOR based on RECIST 1.1 will be listed.   
5.6. 
Pharmacodynamic and Biomarker Analysis 
As the study was terminated for phase 2 portion due to the interim monitoring for efficacy.  The final 
CSR will focus on the safety updates for the study as a synoptic CSR.  As a result, there will no analysis 
included for PD and Biomarker portion.   


  
 
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REFERENCES  
Protocol amendment Version 6.0,  20210722.   
Brookmeyer R, Crowley JJ. A confidence interval for the median survival time. Biometrics. 38:29-41, 
1982. 
Eisenhauer EA, P. Therasse, J. Bogerts et al. New Response evaluation criteria in Solid Tumours: 
Revised RECIST Guideline (version 1.1). European Journal of Cancer. 45: 228-247, 2009. 
CA-125 Gynecologic Cancer Inter Group Criteria 
BBI-DSP7888-102CI_aCRF_21Jul2020 FINAL.pdf 
Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, et al. Antitumor 
activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the 
phase II KEYNOTE-100 study. Ann Oncol. 2019;30:1080-1087. 
 
 


  
 
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APPENDIX 1. RESPONSE EVALUATION CRITERIA IN SOLID 
TUMORS  
Response Evaluation Criteria in Solid Tumors  
Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), will be used by local site 
Investigators to assess tumor response and progression and make treatment decisions. 
https://ctep.cancer.gov/protocoldevelopment/docs/recist_guideline.pdf 
 
Treatment decision 
 
If a patients experiences objective disease progression according to RECIST (v 1.1) and is clinically 
stable, patients will continue on treatment with study drug until patients experiences immune 
confirmed PD (iCPD) per iRECIST. 
 
Clinical Stability is defined as: 
-No worsening of performance status 
-No clinically relevant increase in disease-related symptoms 
-No requirement for intensified management of disease-related symptoms (such as analgesics, 
radiation, or palliative care)  
 
Patients who remain on study treatment following objective disease progression per RECIST (v.1.1) 
will continue to be evaluated for objective response to study treatment according to the SOA and 
evaluated according to iRECIST 
 
Summary: 
Evaluation of Target Lesions 
Complete Response (CR):  Disappearance of all target lesions.  Any pathological lymph nodes 
(whether target or non-target) must have reduction in short axis to <10 mm. 
Partial Response (PR):  At least a 30% decrease in the sum of the diameters of target lesions, taking 
as reference the baseline sum diameters. 
Progressive Disease (PD):  At least a 20% increase in the sum of the diameters of target lesions, 
taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on 
study).  In addition to the relative increase of 20%, the sum must also demonstrate an absolute 
increase of at least 5 mm.  (Note:  the appearance of one or more new lesions is also considered 
progression). 
Stable Disease (SD):  Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify 
for PD, taking as reference the smallest sum diameters while on study. 
Evaluation of Non-Target Lesions 
Complete Response (CR):  Disappearance of all non-target lesions and normalization of tumor 
marker level.  All lymph nodes must be non-pathological in size (< 10 mm short axis). 


  
 
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Note:  If tumor markers are initially above the upper normal limit, they must normalize for a patient 
to be considered in complete clinical response. 
Non-CR/Non-PD:  Persistence of one or more non-target lesion(s) and/or maintenance of tumor 
marker level above the normal limits. 
Progressive Disease (PD):  Appearance of one or more new lesions and/or unequivocal progression 
of existing non-target lesions.  Unequivocal progression should not normally trump target lesion 
status.  It must be representative of overall disease status change, not a single lesion increase. 
Although a clear progression of “non-target” lesions only is exceptional, the opinion of the treating 
physician should prevail in such circumstances; and the progression status should be confirmed at a 
later time by the review panel (or Principal Investigator). 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment until disease 
progression/recurrence (taking as reference for progressive disease the smallest measurements 
recorded since the treatment started).  The patient's best response assignment will depend on the 
achievement of both measurement and confirmation criteria. 
RECIST Response for Patients with Measurable Disease (ie, Target Disease) 
Target Lesions 
Non-Target Lesions New Lesions 
Overall 
Response 
Best Overall Response 
when Confirmation is 
Required* 
CR 
CR 
No 
CR 
> 4 wks. 
Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
> 4 wks. 
Confirmation** 
CR 
Not evaluated 
No 
PR 
PR 
Non-CR/Non-
PD/not evaluated 
No 
PR 
SD 
Non-CR/Non-
PD/not evaluated 
No 
SD 
Documented at least 
once > 6 weeks from 
baseline** 
PD 
Any 
Yes or No 
PD 
No prior SD, PR or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
Abbreviations:  CR = complete response; PD = progressive disease; PR = partial response; SD = 
stable disease. 
*See RECIST v1.1 publication for further details on what is evidence of a new lesion. 


  
 
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**Only for non-randomized trials with response as primary endpoint. 
***In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as 
disease progression. 
Note:     Patients with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be reported as “symptomatic 
deterioration.”  Every effort should be made to document the objective progression even after 
discontinuation of treatment. 
 
RECIST Response for Patients with Non-Measurable Disease (ie, Non-Target Disease) 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
Abbreviations: CR = complete response; PD = progressive disease 
*‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly 
used as an endpoint for assessment of efficacy in some trials so to assign this category when no 
lesions can be measured is not advised