Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination With Nivolumab in Subjects With Locally Advanced or Metastatic Solid Tumors
Phase: PHASE1
Conditions: Solid Tumor, Cancer, Carcinoma, Hepatocellular Carcinoma, HCC
Sponsor: Kyowa Kirin, Inc.

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
CONFIDENTIAL 
1 
 
CLINICAL PROTOCOL 
 
Protocol Title: 
Open-label, Multicenter Phase 1/2 Study of Mogamulizumab in 
Combination with Nivolumab in Subjects with Locally 
Advanced or Metastatic Solid Tumors 
Protocol Number: 
0761-014 
Original Protocol: 
13OCT2015  
Amendment 1: 
08DEC2015 
Amendment 2: 
05DEC2016 
Amendment 3: 
28SEP2018 
US IND Number: 
126,887 
Sponsor: 
Kyowa Kirin Pharmaceutical Development, Inc. 
212 Carnegie Center, Suite 400 
Princeton, NJ  08540 
Sponsor’s Responsible 
Medical Monitor: 
 
 
 
 
 
 
 
 
 
 
 
 
Confidentiality Statement 
The information contained in this document is the property of or under the control of Kyowa Kirin 
Pharmaceutical Development, Inc, and its affiliated companies. This information is provided to you in 
confidence as an Investigator, potential Investigator or consultant, for review by you, your staff and applicable 
Institutional Review Board/Ethics Committee. You shall not disclose this information to others without prior 
written authorization from Kyowa Kirin Pharmaceutical Development, Inc., except to the extent necessary to 
obtain informed consent from those persons to whom the drug may be administered, and except as may be 
required by federal, state, or local laws or regulations. 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
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Principal Investigator Signature Page 
Protocol Title: Open-label, Multicenter Phase 1/2 Study of Mogamulizumab in Combination 
with Nivolumab in Subjects with Locally Advanced or Metastatic Solid 
Tumors 
Protocol Number: 0761-014, Amendment 3 
This protocol contains information that is proprietary to the Sponsor, Kyowa Kirin 
Pharmaceutical Development, Inc. (KKD; herein after referred to as the Sponsor). This 
information is being provided to you for the purpose of conducting a clinical trial on behalf of 
KKD. You may disclose the contents of this protocol to the study personnel under your 
supervision and to your Institutional Review Board (IRB) or Ethics Committee (EC). As a 
Principal Investigator participating in this study you agree to not disclose the contents of this 
protocol to any other parties (unless such disclosure is required by government regulations or 
laws) without the prior written permission of KKD. 
Any supplemental information (e.g., protocol amendment, Investigator Brochure [IB], study 
manuals) that may accompany this document is also proprietary to KKD and should be 
handled consistent with the terms stated above. 
I, the undersigned, have reviewed this protocol, including Appendices and I agree to conduct 
the clinical study in compliance with the protocol and study manuals, and with ethical 
principles that have their origin in the Declaration of Helsinki and are consistent with the 
International Conference on Harmonisation (ICH) guidelines on Good Clinical Practice 
(GCP), any applicable laws and requirements, and any conditions required by a regulatory 
authority and/or IRB/EC.  
I understand that the protocol may not be modified without written approval of the sponsor. 
All changes to the protocol must be submitted to the applicable regulatory authority and 
IRB/EC, and must be approved by the IRB/EC prior to implementation except when 
necessary to eliminate immediate hazards to the subjects or when the change(s), as deemed 
by the Sponsor, involves only logistical or administrative changes. 
Principal Investigator: 
________________________________________  
 
 
 
 
 
Signature 
 
 
 
 
 
Date 
 
________________________________________  
 
 
 
 
 
Printed Name  
 
 
 
 
Title  
 
________________________________________  
 
 
 
 
 
Institution Address 
 
 
 
 
Telephone Number  

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
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Protocol Signature Page 
Protocol Title: Open-label, Multicenter Phase 1/2 Study of Mogamulizumab in Combination 
with Nivolumab in Subjects with Locally Advanced or Metastatic Solid 
Tumors 
Protocol Number:  0761-014, Amendment 3 
 
 
 
 
  
 
 
Date 
 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
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Summary of Changes 
It is anticipated that some subjects will be continuing to receive study treatment at the time of 
data cutoff for completion of analyses and preparation of the clinical study report (CSR).  A 
new section (Section 9.5) has been added to the protocol in this amendment to allow for these 
subjects to continue to receive study treatment and to be followed according to institutional 
standard of care for subsequent assessment of efficacy and safety. 
1) For subjects who are continuing to receive study treatment at the time of data cutoff, 
the Sponsor will continue to supply study drug (mogamulizumab and nivolumab) 
until the subject has completed the maximum treatment period of 96 weeks from 
Cycle 1 Day 1 (Section 6.3) or until the subject meets one of the criteria for removal 
from therapy as described in Section 7.5.   
2) For all ongoing subjects, i.e., subjects who are continuing to receive study treatment 
or who are in safety or survival follow-up at the time of data cutoff, the following 
changes in study procedures and data collection will be implemented: 
• 
Assessments of disease status and safety/tolerability, as well as decisions 
regarding continuation of study treatment, will be made according to 
institutional standard of care as determined by the Principal Investigator. 
• 
Central laboratory analysis of samples will no longer be required. 
• 
Blood samples for pharmacokinetic (PK), pharmacodynamic (PD) and anti-drug 
antibody (ADA) analyses will no longer be collected. 
• 
Survival follow-up will be discontinued for all subjects.  
• 
Electronic data capture will be terminated for all subjects and all data upon 
notification from the Sponsor. 
• 
For subjects who are continuing to receive study treatment at the time of 
implementation of this amendment, SAEs and treatment-related AEs will be 
reported to the KKD Drug Safety Surveillance Department using the SAE form. 
References to Section 9.5 have been added as relevant in other protocol sections. 
Additional changes to the protocol include an update of the Sponsor address and 
identification of a new Medical Monitor for the study.  
 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
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1 
SYNOPSIS 
Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
Investigators and Study Center(s): Up to 23 sites in the United States (US) 
Phase of Development:  1/2 
Objectives:  
Primary: 
To characterize the safety and tolerability and determine the maximum tolerated dose (MTD) or the highest 
protocol-defined dose in the absence of exceeding the MTD, of the combination regimen of mogamulizumab 
and nivolumab in subjects with locally advanced or metastatic solid tumors. 
Secondary: 
• 
To evaluate the anti-tumor activity of the combination of mogamulizumab and nivolumab based on the 
Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v. 1.1). Anti-tumor activity will be 
assessed as overall response rate (ORR), time to response (TTR), duration of response (DOR), 
progression-free survival (PFS), and overall survival (OS). 
Exploratory: 
• 
To assess serum concentrations of mogamulizumab and nivolumab when administered in combination. 
• 
To evaluate the immunogenicity of mogamulizumab and nivolumab when administered in combination. 
• 
To evaluate the pharmacodynamic (PD) profile of the combination of mogamulizumab and nivolumab and 
determine which biomarkers may correlate with safety and/or anti-tumor activity. 
• 
To evaluate the ORR of the combination of mogamulizumab and nivolumab based on the immune-related 
RECIST (irRECIST) v 1.1. 
Study Design: 
This is a multicenter, Phase 1/2, open-label, dose-finding, cohort-expansion study of the anti-CCR4 antibody 
mogamulizumab in combination therapy with the anti-programmed death receptor-1 (PD-1) antibody nivolumab 
in adult subjects with locally advanced or metastatic solid tumors. Subjects will be screened for entry into this 
study after signing the informed consent form (ICF). Subjects who meet study entry criteria will enter the 
treatment cohort that is open to enrollment. The study includes a Phase 1 dose finding and a Phase 2 cohort 
expansion: 
• 
Phase 1 dose finding has a 3+3 design that will identify the MTD or the highest protocol-defined dose, in 
the absence of exceeding the MTD, for the combination regimen and will enroll up to 12 subjects (3 to 
6 subjects per cohort).  
• 
Phase 2 cohort expansion will explore the safety, pharmacokinetic (PK), PD, and anti-tumor activity of the 
highest tolerated dose of the combination regimen and will enroll up to 184 subjects (21 to 36 per tumor 
type) in up to 7 tumor-specific expansion cohorts. 
All subjects will receive 240 mg of nivolumab as at least a 30-minute intravenous (iv) infusion on Days 1 and 
15 of each 28-day cycle. Subjects will then receive the cohort-assigned dose of mogamulizumab as at least a 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
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Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
1-hour iv infusion on Days 1, 8, 15, and 22 of the first cycle and on Days 1 and 15 of subsequent cycles. When 
both nivolumab and mogamulizumab are administered at the same visit, the infusion of mogamulizumab will be 
started at least 30 minutes after the end of the infusion of nivolumab. Subjects should be closely monitored for 
adverse events (AEs) for at least: 
• 
30 minutes after the completion of the nivolumab infusion; 
• 
4 hours after the completion of the mogamulizumab infusion for the first 2 combination infusions (i.e., 
Cycle 1, Days 1 and 15); and  
• 
30 minutes after all other mogamulizumab infusions. 
Subjects will be monitored for safety throughout the study. Tumor assessments will be performed during the 
Screening period, at Week 10, then at least every 12 weeks thereafter until unequivocal disease progression or 
death. Tumor biopsies will be required during the Screening period (except for the subjects who present archival 
tumor tissues) and at Week 10 (unless the tumor is inaccessible for biopsy). Pharmacokinetic and PD parameters 
and immunogenicity will be determined for mogamulizumab and nivolumab.  
The first post-treatment follow-up visit will be 30 days (± 5 days) after the last dose of investigational medicinal 
product(s) (IMP[s]). The second follow-up visit will be 100-110 days after the last dose of IMP. Adverse events 
and SAEs with onset up to 100 days after the last dose of IMP should be reported, as should any SAEs that 
occur after that time and are considered potentially related to IMPs or study procedures. Subjects will be 
contacted at least every 100 days after the last dose for survival follow up and recording of new anti-cancer 
therapies. All new treatments for cancer should be recorded, including nivolumab if received after 
discontinuation from this study. Subjects who complete or discontinue treatment without progression will have 
tumor assessments collected until a new anti-cancer therapy is started, unequivocal disease progression is 
documented, or death. 
Procedures to be followed for subjects who are ongoing in the study (i.e., subjects who are continuing to receive 
study treatment or who are in safety or survival follow-up) at the time of data cutoff for completion of analyses 
and preparation of the clinical study report (CSR) are described in Section 9.5. 
Phase 1: Dose-finding: 
The dose levels and schedules are described below. 
 
Dose Level 
Dosage of Mogamulizumab 
Dosage of Nivolumab 
Cycle 1 
(Days 1, 8, 15, 22) 
Subsequent Cycles 
(Days 1, 15) 
All Cycles 
(Days 1, 15) 
1 
1.0 mg/kg 
1.0 mg/kg 
240 mg 
Optionala 
0.3 mg/kg 
0.3 mg/kg 
240 mg 
a: This dose level may be enrolled if > 1 subject experiences dose-limiting toxicity at Dose Level 1. 
  

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
CONFIDENTIAL 
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Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
Dose-finding Criteria: 
A Safety Review Committee (SRC) composed of physician(s) from the Sponsor and/or designee and 
Investigators will review cumulative safety data from all subjects before deciding whether to change the dose 
level or open the expansion cohorts. Dose finding will continue until an MTD has been established or it is 
determined that the expansion cohorts should open or that dosing should stop. Further exploration of 
intermediate doses may take place based on evaluation of emerging safety and PK/PD parameters in the current 
trial as well as other ongoing trials. 
Definition of Dose-limiting Toxicity: 
A dose-limiting toxicity (DLT) is defined as the occurrence of any of the following toxicities that are considered 
related to IMP, with onset from the first dose to 14 days after the last dose of IMP in Cycle 1: 
Hematologic Toxicity: 
1) Grade 3 thrombocytopenia with clinically significant bleeding; 
2) Grade 4 thrombocytopenia; 
3) Febrile neutropenia (absolute neutrophil count < 500/mm3 with a single temperature of > 38.3°C 
[101°F]; 
4) Grade 4 neutropenia of duration > 7 days; 
Note: Grade ≥ 3 lymphopenia or leukopenia of any duration is not considered a DLT. 
Non-hematologic Toxicity: 
5) Aspartate transaminase (AST) or alanine transaminase (ALT) elevation > 5 to ≤ 10 times the upper 
limit of normal (ULN) (Grade 3) that does not downgrade to ≤ Grade 1 (or to baseline grade if  > Grade 
1 at baseline)within 14 days; 
6) AST or ALT elevation > 10 times ULN; 
7) Total bilirubin > 5 times ULN; 
8) ALT or AST elevation > 3 times ULN AND concomitant total bilirubin > 2 times ULN, without initial 
findings of cholestasis (elevated serum alkaline phosphatase), AND no other immediately apparent 
possible causes of ALT/AST elevation and hyperbilirubinemia, including, but not limited to, tumor 
progression, viral hepatitis, pre-existing chronic or acute liver disease, or the administration of other 
drug(s) known to be hepatotoxic; 
9) A ≥ Grade 3 non-hematologic laboratory AE (other than AST, ALT, or bilirubin) is a DLT only if it 
requires medical intervention or hospitalization. Exception: Grade 3 or Grade 4 electrolyte 
abnormalities that are not associated with clinical signs or symptoms, and either resolve spontaneously 
or respond to conventional medical intervention are not DLTs; 
Note: ≥ Grade 3 elevation of amylase and/or lipase of any duration not associated with clinical or 
radiographic evidence of pancreatitis is not a DLT; 
10) Grade 4 non-hematologic non-laboratory AE; 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
CONFIDENTIAL 
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Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
11) Grade 3 skin rash that does not improve to ≤ Grade 2 within 3 days of initiation of maximal supportive 
care; 
12) Grade 3 uveitis, bronchospasm, or neurologic toxicity of any duration; 
13) Any other Grade 3 non-hematologic non-laboratory AE lasting > 7 days, with the following exceptions: 
a) Grade 3 inflammatory reaction attributed to a local antitumor response (e.g., inflammatory 
reaction at sites of metastatic disease, lymph nodes, tumor lysis syndrome) is not a DLT; 
b) Grade 3 fatigue is not a DLT; 
c) Grade 3 fever not associated with hemodynamic compromise is not a DLT; 
14) Grade 2 or higher pneumonitis of any duration; 
15) Any Grade 2 uveitis, eye pain, or blurred vision that does not respond to topical therapy and does not 
improve to Grade 1 within 14 days OR requires systemic treatment. 
Phase 2: Cohort expansion  
To further characterize the safety, tolerability, and anti-tumor activity of the combination, up to 184 subjects 
(21 to 36 subjects per tumor type) with locally advanced or metastatic disease in the following tumor types will 
be enrolled: squamous cell non-small cell lung cancer (NSCLC); programmed cell death ligand 1 (PD-L1)-non-
expressing non-squamous cell NSCLC; squamous cell carcinoma of the head and neck (SCCHN); colorectal 
carcinoma, non-microsatellite instability (non-MSI) high; ovarian cancer, hepatocellular carcinoma (HCC), and 
pancreatic adenocarcinoma. PD-L1 expressing is defined as membrane staining observed in ≥ 1% tumor cells 
among a minimum of 100 evaluable tumor cells. Subjects will be treated with the highest dose of the 
combination regimen that was considered tolerable in Phase 1. The safety and tolerability of the dosing regimen 
used in each expansion cohort will be monitored. The SRC will review cumulative safety data from all subjects 
approximately every 2 months during the enrollment period. Clinical safety in the expansion cohorts will be 
monitored continually. 
Selection of Subjects: 
Study populations for this study are: 
• 
Phase 1 dose finding: Adult subjects with locally advanced or metastatic solid tumors. 
• 
Phase 2 cohort expansion: Adult subjects with locally advanced or metastatic squamous cell NSCLC; 
PD-L1 non-expressing non-squamous cell NSCLC; SCCHN; colorectal carcinoma non-MSI high;  ovarian 
cancer (including primary peritoneal cancer and fallopian tube carcinoma); HCC; and pancreatic 
adenocarcinoma. 
Inclusion Criteria:    
Subjects must meet each one of the following inclusion criteria during the Screening period in order to be 
eligible for participation in the study. In addition, subjects participating in Phase 2 must meet all the inclusion 
criteria and have none of the exclusion criteria for the relevant tumor type. 
1) Subject is age 18 years or older; 
2) Subject must have histologically or cytologically confirmed solid tumor; 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
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Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
3) Subjects must have locally advanced or metastatic solid tumor;
4) Subject has received appropriate cancer therapy as defined by: 
a) For subjects in Phase 1: Subject has no additional therapy options available known to prolong 
survival with the exception of PD-1 blockade (Subjects with tumors for which nivolumab has survival 
benefit who have not received PD-1 blockade are eligible.) Prior therapy is not required for a subject 
with a tumor type that has no standard treatment regimen that is considered by the Investigator to be 
appropriate; 
OR subject meets prior therapy requirements for their tumor type provided below in the Additional 
Eligibility Criteria for Subjects in Phase 2; 
Note: Subjects in Phase 1 with NSCLC of non-squamous histology must be tested for epidermal 
growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangement. 
Subjects with EGFR activating mutations or ALK rearrangement must have progressed during or 
after, or been intolerant to, at least one prior approved EGFR or ALK targeted therapy; 
b) For subjects in Phase 2, see prior therapy requirements provided below in the Additional Eligibility 
Criteria for Subjects in Phase 2; 
5) Subject has at least 1 measurable lesion per RECIST v. 1.1. Note: Lesions located in a previously 
irradiated field must have subsequent radiographic disease progression in that site in order to be 
considered measurable; 
6) Subject has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1; 
7) If the subject is a woman of child-bearing potential or man who is sexually active with woman of 
child-bearing potential, the subject agrees to use adequate contraception from signing of the ICF, for the 
duration of study participation; and for 23 weeks after the last dose of IMP for women or 31 weeks after 
the last dose of IMP for men. 
8) Subject must have adequate hematological, renal, hepatic and respiratory functions defined below: 
a) 
White blood cell count ≥ 2.0 × 109/L (2000/ mm3); 
b) 
Absolute neutrophil count > 1.5 × 109/L (1500/mm3); 
c) 
Platelets > 90 × 109/L (90000/mm3), or >60 × 109/L (60000/mm3) for subjects with hepatocellular 
carcinoma; 
d) 
Hemoglobin ≥ 9.0 g/dL (5.6 mmol/L); 
e) 
Serum total bilirubin ≤ 1.5 × ULN (except subjects with hepatocellular carcinoma or Gilbert 
syndrome, who can have total bilirubin < 3.0 mg/dL); 
f) 
AST and ALT ≤ 3 × ULN, or ≤ 5 × ULN for subjects with liver metastases or hepatocellular 
carcinoma; 
g) 
Serum creatinine ≤ 1.5 × ULN OR calculated creatinine clearance (CrCL) ≥ 40 mL/min (using the 
Cockcroft-Gault formula) 
– 
Female CrCL = (140-age in years) × weight in kg × 0.85 
 
 
                  72 × serum creatinine in mg/dL 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
CONFIDENTIAL 
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Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
– 
Male CrCL = (140-age in years) × weight in kg × 1.00
 
  
               72 × serum creatinine in mg/dL; 
9) The subject is willing to undergo tumor biopsy during the Screening period, or, if the tumor is inaccessible 
for biopsy, archived tumor material must be available for submission; 
10) The subject is able to understand and willing to sign a written ICF. 
Exclusion Criteria: 
Subjects will not be eligible to participate in this study if any of the following exclusion criteria is met during 
the Screening period. In addition, subjects participating in Phase 2 must meet all the inclusion criteria and have 
none of the exclusion criteria specified for the relevant tumor type. 
1) Female subject who is pregnant or breast-feeding, or any subject expecting to conceive or father a child 
during his study; 
2) Subject has an uncontrolled intercurrent illness that in the opinion of the Investigator would 
compromise the safety of the subject. These may include, but not limited to, uncontrolled infection, 
unstable angina, interstitial lung disease, or clinically significant cardiac arrhythmia;  
3) Subject has a psychiatric illness/social situations that in the opinion of the Investigator would limit 
compliance with study requirements; 
4) Subject has a primary central nervous system (CNS) tumor or known CNS metastases and/or history of 
CNS metastases and/or carcinomatous meningitis;  Exception: Subjects are eligible if CNS metastases 
are adequately treated and subjects are neurologically returned to baseline (except for residual signs or 
symptoms related to the CNS treatment) for at least 4 weeks prior to enrollment. In addition, subjects 
must be off corticosteroids for 4 weeks prior to enrollment 
5) Subject has received prior therapy for cancer or major surgery within 28 days, or 42 days for 
nitrosourea or mitomycin C, prior to Cycle 1 Day 1, or 14 days for tamoxifen; 
6) Subject has received radiotherapy or radiosurgery within 14 days prior to Cycle 1 Day 1;  
7) Subject has been previously treated with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti CD137, or anti-
cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody or any other antibody or drug 
specifically targeting T-cell co-stimulation or checkpoint pathways; 
8) Subject has been previously treated with mogamulizumab; 
9) Subject has a history of allergy or hypersensitivity to study drug components; 
10) Subject has received a live, attenuated vaccine within 28 days prior to Cycle 1 Day 1; 
11) Subject has a history of organ transplant or allogeneic bone marrow transplant; 
12) Subject has any unresolved toxicity Grade > 1 (defined by Common Terminology Criteria for Adverse 
Events version 4.03 [CTCAE v. 4.03]) from previous anti-cancer therapy, excluding alopecia, fatigue, 
and laboratory values listed in the inclusion criteria. Subjects with irreversible toxicity that is not 
reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing 
loss) at the discretion of the Investigator; 
13) Subject use of immunosuppressive medication within 14 days before the Cycle 1 Day 1. Note: Inhaled, 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
CONFIDENTIAL 
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Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
ocular, intranasal, intra-articular, or topical corticosteroids are allowed. Non-immunosuppressive doses 
of systemic steroids for adrenal replacement or for contrast allergy are allowed; 
14) Subject has an active autoimmune disease or a history of autoimmune disease which may affect vital 
organ function or require immune suppressive treatment including systemic corticosteroids; these 
include but are not limited to subjects with a history of immune-related neurologic disease, multiple 
sclerosis, uveitis, autoimmune (demyelinating) neuropathy, Guillain-Barré syndrome, myasthenia 
gravis; transverse myelitis; systemic autoimmune disease such as systemic lupus erythematosus, 
connective tissue diseases, scleroderma, autoimmune hepatitis; 
a) Exceptions: Subject with vitiligo, alopecia, type I diabetes mellitus, and endocrine deficiencies 
including hypothyroidism managed with replacement hormones including physiologic 
corticosteroids are eligible. Subject with psoriasis controlled with topical medication, or conditions 
not expected to recur in the absence of an external trigger (precipitating event) are eligible; 
15) Subject has a history of toxic epidermal necrolysis or Stevens-Johnson syndrome; 
16) Subject has a history of inflammatory bowel disease, Crohn’s disease, ulcerative colitis, or Wegener’s 
granulomatosis; 
17) Subject has primary or acquired immunodeficiency or known history of testing positive for human 
immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome;  
18) Subject who tests positive for hepatitis B surface antigen (HBVsAg) or hepatitis C RNA indicating 
acute or chronic infection except for subjects with hepatocellular carcinoma; 
19) Subject has another active malignancy requiring concurrent intervention;  
20) Subject who is receiving any other investigational agents;  
21) Subject has another condition that, in the opinion of the Investigator and/or Sponsor, would interfere 
with evaluation of the IMP or interpretation of subject safety or study results; 
22) Subject has a history of pneumonitis or interstitial lung disease. 
Additional Eligibility Criteria for Subjects in Phase 2 
In addition to having to meet all the above-mentioned inclusion criteria and have none of the exclusion criteria, 
subjects must meet the following inclusion criteria and have none of the exclusion criteria for the relevant tumor 
type during the Screening period in order to be eligible for participation in the Phase 2 of the study: 
NSCLC, Squamous Cell: 
Inclusion Criteria: 
1) Subjects with histologically or cytologically confirmed Stage IIIB or Stage IV (according to version 7 
of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology; 
see Procedure Manual) squamous cell NSCLC; 
2) Prior Therapy: Subject experienced disease recurrence or progression during or after platinum 
doublet-based chemotherapy for advanced or metastatic disease; 
a) Subject with recurrent or progressive disease within 6 months after completing platinum-based 
chemotherapy for local disease are eligible; 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
CONFIDENTIAL 
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Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
b) Subject with recurrent or progressive disease > 6 months after platinum-containing adjuvant, 
neoadjuvant or definitive chemoradiation therapy given for local disease, who also subsequently 
progressed during or after a platinum doublet-based regimen given to treat the recurrence, are 
eligible. 
NSCLC, Nonsquamous, PD-L1 Non-expressing: 
Inclusion Criteria: 
1) Subject with histologically or cytologically confirmed Stage IIIB or Stage IV (according to version 7 of 
the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology; see 
Procedure Manual) non-squamous cell NSCLC; 
2) Subject’s tumor must be PD-L1 non-expressing on immunohistochemistry (IHC) testing performed by 
the central laboratory during the Screening period. Either a formalin-fixed, paraffin-embedded (FFPE) 
tissue block or tumor tissue sections must be submitted for biomarker evaluation during the Screening 
period. The tumor tissue sample may be fresh or archival. Tissue must be a core needle biopsy, 
excisional or incisional biopsy. Fine needle biopsies, drainage of pleural effusions with cytospins, or 
punch biopsies are not considered adequate for biomarker review. Biopsies of bone lesions that do not 
have a soft tissue component or decalcified bone tumor samples are also not acceptable; 
3) Prior Therapy: Subject experienced disease recurrence or progression during or after platinum 
doublet-based chemotherapy regimen for advanced or metastatic disease; 
a) Subjects with recurrent or progressive disease within 6 months after completing platinum-based 
chemotherapy for local disease are eligible; 
b) Subjects with recurrent or progressive disease > 6 months after platinum-containing adjuvant, 
neoadjuvant or definitive chemoradiation therapy given for local disease, who also subsequently 
progressed during or after a platinum doublet-based regimen given to treat the recurrence, are 
eligible; 
c) Subjects must be tested for EGFR mutations and ALK rearrangement. Subjects with EGFR 
activating mutations or ALK rearrangement must have progressed during or after, or been 
intolerant to, at least one prior approved EGFR or ALK targeted therapy. 
Squamous Cell Carcinoma of Head and Neck: 
Inclusion Criteria: 
1) Histologically confirmed squamous cell carcinoma of oral cavity, pharynx, or larynx; Squamous cell 
carcinoma of unknown primary is allowed only if tumor is HPV16 positive; 
2) Stage III or IV and not amenable to local therapy with curative intent (surgery or radiation therapy with 
or without chemotherapy); 
3) Prior Therapy: Tumor progression or recurrence within 6 months of last dose of platinum therapy in the 
adjuvant (i.e., with radiation after surgery), primary (i.e., with radiation), recurrent, or metastatic 
setting. Clinical progression after platinum therapy is an allowable event for entry and is defined as 
progression of a lesion at least 10 mm in size that is amenable to caliper measurement (e.g., superficial 
skin lesion as per RECIST v 1.1) or a lesion that has been visualized and photographically recorded 
with measurements and shown to have progressed. 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
CONFIDENTIAL 
13 
 
Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
Exclusion Criteria: 
1) Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx or salivary gland; 
2) Subject with base of skull lesion(s) with possible dural or brain parenchymal involvement that may 
require local therapy, e.g., radiation; 
3) Non-squamous histologies (e.g., mucosal melanoma); 
Colorectal Carcinoma, non-MSI high: 
Inclusion Criteria:  
1) Subject has histologically confirmed metastatic or recurrent colorectal carcinoma; 
2) Microsatellite instability status - low (MSI-L) or microsatellite stable (MSS) as detected by an 
accredited laboratory per local procedures, see Section 9.2.7.1. 
3) Prior treatment: Progression during, after, or been intolerant following the last administration of 
approved standard therapies, which must include at minimum a fluoropyrimidine, oxaliplatin, and 
irinotecan, as well as at least one of the following agents, if approved or in standard national 
guidelines, bevacizumab, cetuximab or panitumumab (if KRAS wild type), or regorafenib. 
Exclusion Criterion:  
1) MSI high (MSI-H) tumor status detected by an accredited laboratory per local procedures. 
Ovarian Cancer: 
Inclusion Criteria: 
1) Female subjects with International Federation of Gynecology and Obstetrics Stage Ic, Stage II, 
Stage III, Stage IV, recurrent, or persistent (unresectable) histologically confirmed epithelial ovarian 
cancer, primary peritoneal cancer, or fallopian tube carcinoma; 
2) Subjects are allowed to have received up to 4 prior cytotoxic regimens for treatment of their epithelial 
ovarian, fallopian tube, or primary peritoneal cancer; they must have had one prior platinum-based 
chemotherapeutic regimen for management of primary disease, possibly including intra-peritoneal 
therapy, consolidation, biologic/targeted (non-cytotoxic) agents (e.g., bevacizumab) or extended 
therapy administered after surgical or non-surgical assessment; subjects are allowed to have received, 
but are not required to have received, 1 to 2 cytotoxic regimens for management of recurrent or 
persistent disease; (for the purposes of this study, poly-adenosine diphosphate (ADP) ribose 
polymerase (PARP) inhibitors given for recurrent or progressive disease will be considered cytotoxic); 
if 2 cytotoxic regimens had been received for management of recurrent or persistent disease, one of 
these regimens would have had to contain either a platinum or taxane agent; 
Platinum-free Interval- Subjects must have progressed < 6 months after completion of their last 
platinum-based chemotherapy; 
3) Albumin greater than or equal to 2.8 g/dL. 
Exclusion Criterion: 
1) Subject has mucinous histology. 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
CONFIDENTIAL 
14 
 
Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
Hepatocellular Carcinoma 
Inclusion Criteria: 
1) Histologically confirmed hepatocellular carcinoma not amenable for management with curative intent 
by surgery or local therapeutic measure; 
2) Subject must have received sorafenib treatment and either:   
• 
have had documented radiographic or symptomatic progression during or after sorafenib therapy; 
OR 
• 
be intolerant of sorafenib (as defined as Grade 2 drug-related adverse event which 1) persisted in 
spite of comprehensive supportive therapy according to institutional standards AND 2) persisted or 
recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose 
level (to 400 mg once daily) AND/OR Grade 3 drug-related adverse event which 1) persisted in 
spite of comprehensive supportive therapy according to institutional standards OR 2) persisted or 
recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose 
level (to 400 mg once daily)in Section 1.4.9;  
OR must have documented refusal of sorafenib; 
3) Subject has Child-Pugh score of ≤6, i.e., Child-Pugh A (Appendix 2); 
4) INR ≤ 2.3 or Prothrombin time (PT) ≤ 6 seconds above control; 
5) Subject has HBV DNA viral load undetectable or < 100 IU/mL at screening.  If subject has detectable 
HBsAg, HBeAg, or HBV DNA (indicating ongoing viral replication of hepatitis B, he/she must be on 
antiviral therapy per regional standard of care guidelines prior to initiation of study therapy. If not on 
antiviral therapy at screening, then the subject must initiate treatment per regional standard of care 
guidelines prior to C1D1 and must be willing to continue antiviral therapy while on study treatment. 
Exclusion Criterion: 
1) Any history of hepatic encephalopathy; 
2) Any prior (within 1 year) or current clinically significant ascites as measured by physical examination 
and that requires  paracentesis for control; 
3) Active coinfection with both hepatitis B (i.e., HBVsAg and/or hepatitis B DNA) and hepatitis C (i.e., 
hepatitic C RNA); 
4) Hepatitis D infection in subjects with hepatitis B; 
5) Any history of clinically meaningful variceal bleeding within the last three months. 
Pancreatic Adenocarcinoma 
Inclusion Criteria: 
1) Subject has histologically or cytologically confirmed locally advanced unresectable or metastatic 
pancreatic ductal adenocarcinoma; 
2) Tumor sample available for MSI testing (Note: archived material is sufficient); 
3) Prior treatment: Subject must have received at least one prior chemotherapy regimen for their disease 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
CONFIDENTIAL 
15 
 
Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
and must have radiological or clinical progression or documented unacceptable toxicity; 
Exclusion Criterion: 
1) Known microsatellite instability-high (MSI-H) tumor status. 
Number of Subjects: Planned: Up to 188 subjects 
• 
Phase 1 dose finding: Up to 12 subjects (3 to 6 subjects per cohort) were planned. Four subjects were 
enrolled. 
• 
Phase 2 expansion cohort: Up to 184 subjects (21 to 36 subjects per cohort in up to 8 tumor-specific 
cohorts). 
Treatment of Subjects: 
Investigational Medicinal Product:  
• 
Mogamulizumab: 0.3 or 1.0 mg/kg administered as an iv infusion over at least 1 hour on Days 1, 8, 15, and 
22 in Cycle 1 then on Days 1 and 15 of each subsequent 28-day cycle.  
• 
Nivolumab: 240 mg of nivolumab administered as an iv infusion over at least 30 minutes on Days 1 and 15 
of each 28-day cycle. 
Duration of Treatment: Subjects may receive the combination therapy for up to 96 weeks from Cycle 1 Day 1. 
Subjects who stop treatment without disease progression and who experience disease progression within 
12 months of their last dose of IMP may receive additional IMP for up to 48 weeks, provided that they have not 
received other systemic therapy for their cancer.  (As of Amendment 3, re-treatment of subjects who stop 
treatment without disease progression will no longer be allowed.) 
Efficacy, Pharmacokinetic/Pharmacodynamic, and Safety Variables: 
Efficacy:  Anti-tumor activity will be evaluated using both RECIST v. 1.1 and irRECIST v. 1.1. Anti-tumor 
activity will be assessed as BOR, TTR, DOR, PFS, and OS. 
Pharmacokinetic: The following PK parameters will be measured: 
• 
Mogamulizumab: observed minimum serum concentration at the end of a dosing interval (Cmin) and 
observed maximum serum concentration (Cmax); 
• 
Nivolumab: Cmin  
Pharmacodynamic: The biomarkers may include, but are not limited to, immune cell subsets and immune 
factors such as cytokines and chemokines in tumor and/or blood. 
Immunogenicity: Anti-mogamulizumab antibody and anti-nivolumab antibody. 
Safety:  Adverse events; clinical laboratory tests (serum chemistry, thyroid function testing, hematology, 
coagulation profile, urinalysis); immunogenicity; vital signs; 12-lead ECGs; physical examination (including 
body weight, etc.) will be evaluated to determine the safety profile in this combination regimen. 
Statistical Methods and Planned Analysis: 
Evaluation of the data for this study will consist primarily of data listings and summary displays. Demographic 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
CONFIDENTIAL 
16 
 
Name of Sponsor/Company: 
Kyowa Kirin Pharmaceutical Development, Inc. 
Name of Finished Product: 
NA 
Name of Active Ingredient: 
Mogamulizumab 
Nivolumab 
Study Title:  Open-label, Multicenter, Phase 1/2 Study of Mogamulizumab in Combination with Nivolumab in 
Subjects With Locally Advanced or Metastatic Solid Tumors 
Protocol Number:  0761-014 
and other baseline characteristic information will be summarized for the Safety Analysis and Efficacy Analysis 
Sets. Adverse events will be tabulated by body system, severity, and relation to treatment. Similar presentations 
will be provided for SAEs, AEs leading to discontinuation of IMP and AEs leading to death. The tabulation of 
laboratory parameters will indicate the normal range for each parameter. Each value will be classified as falling 
above, below, or within the normal range.  
Individual serum concentrations at each sampling time point for mogamulizumab and nivolumab will be 
presented in listings. Descriptive summary statistics of serum concentrations including means, geometric means, 
ranges, standard deviations, and coefficient of variation will be presented by dose cohort and by tumor type. 
Dose proportionality will be assessed as appropriate. Population PK analysis will be explored, if appropriate. 
Pharmacodynamic data will be summarized. Changes from baseline in PD parameters may be used as PD 
markers to explore PK/PD, PD-efficacy, and PD-safety relationships, as appropriate. 
The number and percentage of subjects with a positive anti-drug antibody (ADA) test in the screening, 
confirmatory, or neutralizing assays, if applicable, will be presented at each visit and overall for subjects 
exposed to mogamulizumab and nivolumab. Additionally, a summary of subjects who experienced an infusion 
related reaction and had a positive ADA test in the screening, confirmatory, and neutralizing assays, if 
applicable, will be presented. All immunogenicity data will be listed by subject. Immunogenicity may be 
reported for ADA positive status (such as persistent positive, neutralizing positive, only last sample positive, 
baseline positive and other positive) and ADA negative status, relative to baseline. Effect of immunogenicity on 
safety, efficacy, biomarkers and PK may be explored. 
Subjects will be evaluated for tumor response, TTR, DOR, and PFS. The ORR will be calculated as the 
proportion of subjects who are responders, i.e., complete response (CR) and partial response (PR); the 95% 
exact confidence interval for ORR will be calculated. The ORR will be derived using both the RECIST v. 1.1 
and the irRECIST v. 1.1, based on the efficacy-evaluable subjects in the expansion cohorts for combination 
therapy, which includes all subjects who receive combination therapy in Cycle 1 Day 1. Duration of response, 
OS, and PFS will be estimated using the Kaplan-Meier methodology. 
 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
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2 
TABLE OF CONTENTS 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE ...................................................... 2 
PROTOCOL SIGNATURE PAGE ..................................................................................... 3 
SUMMARY OF CHANGES ............................................................................................... 4 
1 
SYNOPSIS ................................................................................................................. 5 
2 
TABLE OF CONTENTS......................................................................................... 17 
LIST OF IN-TEXT TABLES ............................................................................................ 23 
LIST OF IN-TEXT FIGURES .......................................................................................... 23 
LIST OF APPENDICES.................................................................................................... 23 
3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ........................... 24 
4 
INTRODUCTION ................................................................................................... 27 
4.1 
Medical Background .............................................................................................. 27 
4.1.1 
Immunotherapy for Cancer ................................................................................. 27 
4.2 
Investigational Medicinal Products Profile.............................................................. 28 
4.2.1 
Mogamulizumab ................................................................................................. 28 
4.2.1.1 
Nonclinical Experience .................................................................................... 29 
4.2.1.2 
Clinical Pharmacology ..................................................................................... 29 
4.2.1.3 
Clinical Experience .......................................................................................... 30 
4.2.1.4 
Post-marketing Experience .............................................................................. 30 
4.2.2 
Nivolumab .......................................................................................................... 31 
4.2.2.1 
Nonclinical Experience .................................................................................... 31 
4.2.2.2 
Clinical Pharmacology ..................................................................................... 32 
4.2.2.3 
Clinical Experience .......................................................................................... 32 
4.2.3 
Clinical Experience with the Combination of Mogamulizumab and 
Nivolumab .......................................................................................................... 33 
4.3 
Selection of Doses in the Study .............................................................................. 33 
4.3.1 
Mogamulizumab ................................................................................................. 33 
4.3.2 
Nivolumab .......................................................................................................... 34 
4.4 
Rationale for Combination Treatment ..................................................................... 35 
4.5 
Tumor Types for Expansion Cohorts in Phase 2 ..................................................... 37 
4.5.1 
NSCLC Squamous Cell....................................................................................... 38 

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4.5.2 
NSCLC Nonsquamous Cell................................................................................. 38 
4.5.3 
Squamous Cell Carcinoma of the Head and Neck ................................................ 39 
4.5.4 
Colorectal Cancer ............................................................................................... 39 
4.5.5 
Ovarian Cancer ................................................................................................... 40 
4.5.6 
Hepatocellular Carcinoma ................................................................................... 40 
4.5.7 
Pancreatic Adenocarcinoma ................................................................................ 40 
4.6 
Risks and Benefit to Subjects ................................................................................. 40 
5 
OBJECTIVES .......................................................................................................... 41 
5.1 
Primary .................................................................................................................. 41 
5.2 
Secondary............................................................................................................... 41 
5.3 
Exploratory ............................................................................................................ 41 
6 
DESCRIPTION OF STUDY DESIGN AND POPULATION ............................... 41 
6.1 
Study Overview ...................................................................................................... 41 
6.1.1 
Phase 1: Dose Finding ......................................................................................... 42 
6.1.2 
Dose-finding Criteria .......................................................................................... 42 
6.1.2.1 
Definition of Dose-limiting Toxicity ................................................................ 43 
6.1.2.2 
Definition of Maximum Tolerated Dose........................................................... 45 
6.1.3 
Phase 2: Expansion Cohort.................................................................................. 45 
6.2 
Number of Subjects, and Numbers and Location of Investigative Sites ................... 45 
6.3 
Study Duration ....................................................................................................... 45 
7 
SELECTION AND WITHDRAWAL OF SUBJECTS .......................................... 46 
7.1 
Procedures for Enrollment ...................................................................................... 46 
7.2 
Inclusion Criteria .................................................................................................... 46 
7.3 
Exclusion Criteria ................................................................................................... 47 
7.4 
Additional Eligibility Criteria for Subjects in Phase 2 ............................................. 49 
7.4.1 
Non-small-cell Lung Cancer ............................................................................... 49 
7.4.1.1 
Non-small-cell Lung Cancer, Squamous Cell ................................................... 49 
7.4.1.2 
Non-small-cell Lung Cancer, Nonsquamous, PD-L1 Non-expressing .............. 50 
7.4.2 
Squamous Cell Carcinoma of Head and Neck ..................................................... 51 
7.4.3 
Colorectal Carcinoma, non-Microsatellite Instability High .................................. 51 
7.4.4 
Ovarian Cancer ................................................................................................... 52 

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7.4.5 
Hepatocellular Carcinoma ................................................................................... 52 
7.4.6 
Pancreatic Adenocarcinoma ................................................................................ 53 
7.5 
Removal of Subjects from Therapy or Assessment ................................................. 53 
8 
TREATMENTS ....................................................................................................... 55 
8.1 
Identity of Investigational Medicinal Products ........................................................ 55 
8.1.1 
Treatments to be Administered............................................................................ 56 
8.1.2 
Dose Reduction and Dose Delay ......................................................................... 57 
8.1.2.1 
Dose Reduction ............................................................................................... 57 
8.1.2.2 
Dose-delay Criteria .......................................................................................... 57 
8.1.3 
Criteria to Resume Dosing .................................................................................. 58 
8.1.4 
Criteria for Treatment Discontinuation for Toxicity ............................................ 59 
8.1.5 
Treatment Beyond Disease Progression............................................................... 60 
8.1.6 
Re-treatment for Progression during Follow-up ................................................... 61 
8.2 
Management of Infusion-related Reaction and Other Toxicity ................................ 61 
8.2.1 
Premedication ..................................................................................................... 61 
8.2.2 
Treatment of Infusion-related Reactions .............................................................. 61 
8.2.3 
Immune-associated Select Adverse Events of Interest ......................................... 63 
8.2.3.1 
Recommended Management of Hepatic Events in Subjects with 
HCC ................................................................................................................ 64 
8.3 
Method of Assigning Subjects to Treatment Groups ............................................... 65 
8.4 
Blinding/Unblinding ............................................................................................... 65 
8.5 
Concomitant Treatments ......................................................................................... 65 
8.5.1 
Permitted Concomitant Medications.................................................................... 66 
8.5.2 
Prohibited and/or Restricted Treatments .............................................................. 66 
8.5.3 
Contraception...................................................................................................... 67 
8.6 
Treatment Compliance ........................................................................................... 67 
9 
STUDY PROCEDURES.......................................................................................... 67 
9.1 
Screening ............................................................................................................... 70 
9.2 
Baseline and Treatment .......................................................................................... 71 
9.2.1 
Demographics, Medical History, Pre-treatment Adverse Events .......................... 71 
9.2.2 
Assessment of Safety Laboratory Parameters ...................................................... 71 
9.2.3 
Vital Signs .......................................................................................................... 73 

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9.2.4 
Electrocardiograms ............................................................................................. 73 
9.2.5 
Physical 
Examination, 
Eastern 
Cooperative 
Oncology 
Group 
Performance Status, Height, and Body Weight .................................................... 73 
9.2.6 
Disease-response Assessments ............................................................................ 74 
9.2.7 
Tumor Biopsies ................................................................................................... 75 
9.2.7.1 
Microsatellite Instability Testing ...................................................................... 75 
9.2.7.2 
PD-L1 Testing ................................................................................................. 76 
9.3 
End of Treatment .................................................................................................... 76 
9.4 
Post-treatment Follow-up Period ............................................................................ 76 
9.5 
Study Procedures for Subjects Ongoing at the Time of Data Cutoff for 
Completion of Analyses and Preparation of CSR .................................................... 76 
10 
EFFICACY, 
PHARMACOKINETIC, 
SAFETY, 
AND 
OTHER 
VARIABLES............................................................................................................ 78 
10.1 
Study Endpoints ..................................................................................................... 78 
10.2 
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Assessments ................ 78 
10.3 
Safety Assessments ................................................................................................ 80 
10.3.1 
Definitions .......................................................................................................... 81 
10.3.1.1 
Adverse Events ................................................................................................ 81 
10.3.1.2 
Serious Adverse Events ................................................................................... 81 
10.3.1.3 
Causality.......................................................................................................... 82 
10.3.1.4 
Severity ........................................................................................................... 82 
10.3.2 
Adverse Event Reporting .................................................................................... 83 
10.3.2.1 
Reporting Period .............................................................................................. 83 
10.3.2.2 
Reporting Instructions ...................................................................................... 83 
10.3.3 
Other Significant Adverse Events........................................................................ 85 
10.3.3.1 
Urgent Safety Measures ................................................................................... 85 
10.3.3.2 
Adverse Events That Qualify as Dose-limiting Toxicity ................................... 85 
10.3.3.3 
Infusion-related Reactions ............................................................................... 85 
10.3.4 
Overdose............................................................................................................. 86 
10.3.5 
Pregnancy Reporting ........................................................................................... 86 
11 
DATA MANAGEMENT ......................................................................................... 87 
11.1 
Source Data ............................................................................................................ 87 

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11.2 
Access to Data ........................................................................................................ 87 
11.3 
Electronic Case Report Forms ................................................................................ 87 
11.4 
Record Keeping and Archiving ............................................................................... 88 
11.5 
Study Monitoring ................................................................................................... 88 
12 
STATISTICAL METHODS AND PLANNED ANALYSIS .................................. 88 
12.1 
General Statistical Considerations .......................................................................... 88 
12.2 
Populations to be Analyzed .................................................................................... 89 
12.2.1 
Subject Disposition ............................................................................................. 89 
12.2.2 
Demographic and Baseline Disease Characteristics ............................................. 89 
12.2.3 
Prior and Concomitant Medications .................................................................... 90 
12.2.4 
Investigational Medicinal Product Exposure and Compliance ............................. 90 
12.3 
Efficacy Analysis ................................................................................................... 90 
12.3.1 
Sample Size Determination ................................................................................. 90 
12.3.2 
Significance Level .............................................................................................. 92 
12.4 
Pharmacokinetic Analyses ...................................................................................... 92 
12.5 
Pharmacodynamic Analyses ................................................................................... 92 
12.6 
Analysis of Immunogenicity Data........................................................................... 92 
12.7 
Analyses of Safety Data.......................................................................................... 93 
12.8 
Procedures for Missing, Unused and Spurious Data ................................................ 93 
12.9 
Rules for Excluding Subjects from Analysis ........................................................... 93 
12.10 
Procedures for Reporting Deviations from Original Statistical Plan ........................ 94 
13 
ADMINISTRATION, 
DOCUMENTATION, 
AND 
RECORD 
KEEPING ................................................................................................................ 94 
13.1 
Ethics Committee or Institutional Review Board .................................................... 94 
13.2 
Investigator’s Responsibilities ................................................................................ 94 
13.2.1 
Overall Responsibilities ...................................................................................... 94 
13.2.2 
Subject Informed Consent ................................................................................... 94 
13.2.3 
Confidentiality Regarding Study Subjects ........................................................... 95 
13.2.4 
Record Retention ................................................................................................ 95 
13.2.5 
Investigator Information ...................................................................................... 95 
13.2.6 
Compliance with Law, Audit, and Debarment ..................................................... 96 
13.3 
Financial Disclosure ............................................................................................... 97 

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13.4 
Insurance ................................................................................................................ 97 
13.5 
Publication Policy .................................................................................................. 97 
14 
QUALITY ASSURANCE ........................................................................................ 98 
15 
REFERENCES ........................................................................................................ 99 
16 
APPENDICES ....................................................................................................... 101 

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List of In-text Tables 
Table 6.1.1-1 
Dose Levels ................................................................................42 
Table 8.1-1 
Identification of Investigational Medicinal Products ....................55 
Table 8.1.1-1 
Dosing Schedules of Mogamulizumab and Nivolumab During 
Phase 1 and Phase 2 ....................................................................56 
Table 8.2.2-1 
Recommended Management of Infusion-related Reaction ...........62 
Table 8.2.3-1 
Recommended Management of Investigational Medicinal 
Product-related Dermatologic Toxicity ........................................64 
Table 9-1 
Schedule of Events:  Screening and Treatment Periods ................68 
Table 9-2 
Schedule of Events:  Post-treatment Follow-up ...........................70 
Table 9.2.2-1 
Clinical Laboratory Assessments .................................................72 
Table 10.2-1 
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood 
Sampling Schedule ......................................................................80 
Table 10.3.1-1 
Relationship of Adverse Events ...................................................82 
Table 12.3.1-1 
Sample Size Estimation by Tumor Type ......................................91 
 
List of In-text Figures 
Figure 4.4-1 
Depletion of CD4+ CD25+ FOXP3+ Cells ..................................37 
Figure 6.1-1 
Criteria for Dose Finding and Expansion .....................................43 
 
List of Appendices 
Appendix 1 
Response Evaluation Criteria in Solid Tumors, Version 1.1 
(RECIST v. 1.1) ........................................................................ 102 
Appendix 2 
Child-Pugh Score ...................................................................... 112 
 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
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24 
 
3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviations 
ACTH 
adrenocorticotropic hormone 
ADA 
anti-drug antibody 
ADCC 
antibody-dependent cellular cytotoxicity 
ADP 
adenosine diphosphate 
AE 
adverse event 
ALK 
anaplastic lymphoma kinase 
ALT 
alanine transaminase 
AST 
aspartate transaminase 
ATL 
adult T-cell leukemia/lymphoma 
BMS 
Bristol-Myers Squibb 
BOR 
best overall response 
CCR4 
chemokine receptor 4 
CD 
cluster of differentiation 
CDC 
complement dependent cytotoxic 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CL 
clearance 
CNS 
central nervous system 
CR 
complete response 
CRC 
colorectal carcinoma 
CrCL 
creatinine clearance 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTCL 
cutaneous T-cell lymphoma 
CTLA-4 
cytotoxic T-lymphocyte-associated antigen-4  
CT 
computed tomography 
DLT 
dose-limiting toxicity 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
EGFR 
epidermal growth factor receptor 
EOT 
end of treatment 
EU 
European Union 
Fc 
fragment crystallizable 
FDA 
Food and Drug Administration 
FDG- 
fluorodeoxyglucose 
FFPE 
formalin-fixed, paraffin-embedded 
GCP 
Good Clinical Practices 
HBVsAg 
HCC 
Hepatitis B surface antigen 
hepatocellular carcinoma 
HIPAA 
Health Insurance Portability and Accountability Act 

Clinical Protocol 0761-014, Amendment 3 
 
 
 
 
 
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Abbreviations 
HIV 
human immunodeficiency virus 
HPV 
human papillomavirus 
HR 
hazard ratio 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
ICOS 
inducible T-cell costimulator 
ID 
identification 
IFN-γ 
interferon-γ 
IgG 
immunoglobulin G  
IHC 
immunohistochemistry 
IL 
interleukin 
IMP 
investigational medicinal product 
irCR 
irRECIST-defined complete response 
IRB 
Institutional Review Board 
irPD 
irRECIST-defined progressive disease 
irRECIST 
immune-related Response Evaluation Criteria in Solid Tumors 
IRT 
interactive response technology 
iv 
Intravenous 
KKD 
Kyowa Kirin Pharmaceutical Development 
LFT 
Liver function test 
mAb 
monoclonal antibody 
MDC 
macrophage-derived chemokine 
MRI 
magnetic resonance imaging 
MSI 
microsatellite instability 
MSI-H 
microsatellite instability - high 
MSI-L 
microsatellite instability -low 
MSS 
microsatellite - stable 
MTD 
maximum tolerated dose 
NOEAL 
no-observed-adverse-effect level 
NSCLC 
non-small-cell lung cancer 
ORR 
overall response rate 
OS 
overall survival 
PARP 
poly ADP ribose polymerase 
PD 
pharmacodynamic(s) 
PD-1 
programmed death 1 
PD-L1 
programmed cell death ligand 1 
PD-L2 
programmed cell death ligand 2 
PCR 
polymerase chain reaction 
PET 
positron emission tomography 
PFS 
progression-free survival 
PI 
Prescribing Information 
PK 
pharmacokinetic(s) 
PR 
partial response 
PS 
performance status 

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Abbreviations 
PTCL 
peripheral T-cell lymphoma 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
ribonucleic acid  
SAE 
serious adverse event 
SCCHN 
Squamous cell carcinoma of the head and neck 
SCID 
severe combined immunodeficiency 
SRC 
Safety Review Committee 
TARC 
thymus and activation-regulated chemokine 
TEAE 
treatment-emergent adverse event 
Th2 
T-helper 2 subset of T-cells 
TNF-α 
tumor necrosis factor-alpha  
TMTB 
total measured tumor burden 
Treg 
regulatory T-cells 
TTR 
time to response 
ULN 
upper limit of normal 
US 
United States (of America) 
Definitions  
AUC0-7 days 
area under the concentration-time curve from Day 0 to Day 7 
Cmax 
observed peak serum concentration 
Cmin 
observed minimum serum concentration at the end of a dosing interval 
pH 
hydrogen ion concentration 
t1/2 
terminal half-life 

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4 
INTRODUCTION  
4.1 
Medical Background 
4.1.1 
Immunotherapy for Cancer 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 

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4.2 
Investigational Medicinal Products Profile 
4.2.1 
Mogamulizumab 
 
 
 
 
 
 
 
 
 
 

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4.2.1.1 
Nonclinical Experience 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.2.1.2 
Clinical Pharmacology 
 
 
 
 

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4.2.1.3 
Clinical Experience 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.2.1.4 
Post-marketing Experience 
 
 
 
 

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4.2.2 
Nivolumab 
 
 
 
 
 
 
 
 
 
 
4.2.2.1 
Nonclinical Experience 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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4.2.2.2 
Clinical Pharmacology 
 
 
 
 
 
 
 
 
 
 
 
 
4.2.2.3 
Clinical Experience 
 
 
 
 
 
 
 
 
 
 
 

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4.2.3 
Clinical Experience with the Combination of Mogamulizumab and 
Nivolumab 
 
 
 
 
 
 
   
4.3 
Selection of Doses in the Study 
4.3.1 
Mogamulizumab 
 
 
 
 
 
 
 
 
 

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4.3.2 
Nivolumab 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 

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4.4 
Rationale for Combination Treatment 
 
   
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Figure 4.4-1 Depletion of CD4+ CD25+ FOXP3+ Cells 
 
Numbers of CD4+ CD25+ FOXP3+ cells from mogamulizumab–treated subjects with adult T-cell leukemia-lymphoma 
(ATL) in blood samples taken (i) just before the first infusion, (ii) just before the second infusion, (iii) just before the fifth 
infusion, (iv) 1 week after the eighth infusion, and (v) 4 months after the eighth infusion and those from 10 controls are 
shown as box and whisker plots indicating minimum, lower quartile, median, upper quartile, and maximum values. 
 
 
 
 
 
4.5 
Tumor Types for Expansion Cohorts in Phase 2 
 
 
 
 
   

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4.5.1 
NSCLC Squamous Cell  
 
 
 
   
 
 
 
 
 
 
 
   
 
 
 
   
4.5.2 
NSCLC Nonsquamous Cell  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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4.5.3 
Squamous Cell Carcinoma of the Head and Neck 
 
 
 
 
 
 
 
 
 
 
 
   
4.5.4 
Colorectal Cancer 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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4.5.5 
Ovarian Cancer 
 
 
   
4.5.6 
Hepatocellular Carcinoma 
 
 
 
 
 
 
 
 
4.5.7 
Pancreatic Adenocarcinoma 
 
 
 
 
4.6 
Risks and Benefit to Subjects 
 
 
 
 
 
 
 
 
 
 
. 

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5 
OBJECTIVES 
5.1 
Primary 
To characterize the safety and tolerability and determine the maximum tolerated dose (MTD), 
or the highest protocol-defined dose in the absence of exceeding the MTD, of the 
combination regimen of mogamulizumab and nivolumab in subjects with locally advanced or 
metastatic solid tumors. 
5.2 
Secondary 
1) To evaluate the anti-tumor activity of the combination of mogamulizumab and 
nivolumab based on the RECIST v. 1.1. Anti-tumor activity will be assessed as ORR, 
time to response (TTR), duration of response (DOR), PFS, and OS. 
5.3 
Exploratory 
1) To assess serum concentrations of mogamulizumab and nivolumab when 
administered in combination. 
2) To evaluate the immunogenicity of mogamulizumab and nivolumab when 
administered in combination. 
3) To evaluate the PD profile of the combination of mogamulizumab and nivolumab and 
determine which biomarkers may correlate with safety and/or anti-tumor activity. 
4) To evaluate the ORR of the combination of mogamulizumab and nivolumab based on 
the irRECIST v. 1.1. 
6 
DESCRIPTION OF STUDY DESIGN AND POPULATION 
6.1 
Study Overview 
This is a multicenter, Phase 1/2, open-label, dose-finding and cohort-expansion study of the 
anti-CCR4 antibody mogamulizumab in combination therapy with the anti-PD-1 antibody 
nivolumab in adult subjects with locally advanced or metastatic solid tumors. Subjects will be 
screened for entry into this study after signing the informed consent form (ICF). Subjects 
who meet study entry criteria will enter the treatment cohort that is open to enrollment.  
The study includes a Phase 1 dose finding and a Phase 2 cohort-expansion:  
• 
Phase 1 dose-finding has a 3+3 design that will identify the MTD, or the highest 
protocol-defined dose in the absence of exceeding the MTD, for the combination regimen 
and will enroll up to 12 subjects (3 to 6 subjects per cohort).  
• 
Phase 2 cohort-expansion will explore the safety, PK, PD, and anti-tumor activity of the 
highest tolerated dose of the combination regimen and will enroll up to 184 subjects 
(21 to 36 per cohort) in up to 7 tumor-specific expansion cohorts. 

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6.1.1 
Phase 1: Dose Finding  
A starting dose level and an optional dose level are planned. The dose-finding phase will 
enroll up to 12 subjects (3 to 6 subjects per cohort). The dose levels and schedules are 
described in Table 6.1.1-1. 
The MTD is defined as one dose level below the dose level of the cohort where ≥ one-third of 
the subjects experience DLT. The recommended dose regimen for Phase 2 is intended to be 
either the MTD or the highest dose level tested.  
Table 6.1.1-1 
Dose Levels 
Dose Level 
Dosage of Mogamulizumab 
Dosage of Nivolumab 
Cycle 1 
(Days 1, 8, 15, 22) 
Subsequent Cycles 
(Days 1, 15) 
All Cycles 
(Days 1, 15) 
 
 
 
 
 
 
 
a: This dose level may be enrolled if > 1 subject experiences DLT at Dose Level 1. 
DLT=dose limiting toxicity. 
 
A minimum of 3 subjects will be enrolled and treated in each cohort, and all 3 subjects will 
be observed for the DLT observation period (see Section 6.1.2.1). Subjects who are not 
evaluable for DLT will be replaced. All cohorts will have a minimum of 3 DLT-evaluable 
subjects. Cycle 1 Day 1 dosing of subjects in each cohort should be separated by at least 
1 day during Phase 1 of the study. 
6.1.2 
Dose-finding Criteria 
A Safety Review Committee (SRC) composed of physicians from the Sponsor and/or 
designee and Investigators will review cumulative safety data from all subjects before 
deciding whether to change the dose level or open the expansion cohorts.  
The first meeting of the SRC will occur before the study opens to enrollment. At that meeting 
the SRC will discuss the role and responsibilities of the SRC and review the safety data from 
the ongoing 0761-013 Phase 1 study. In that study, nivolumab is administered at 3.0 mg/kg 
and mogamulizumab has been administered at 0.3 mg/kg or 1.0 mg/kg. The SRC may decide 
to open Phase 1 of this study at the optional dose level if there is concern about the safety of 
the combination at the higher dose level in the Japanese trial.   
Dose finding will continue until an MTD has been established or it is determined that the 
expansion cohorts should open or that dosing should stop. Further exploration of intermediate 
doses may take place based on evaluation of emerging safety and PK/PD parameters in the 

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current trial as well as other ongoing trials. The criteria for dose finding are outlined in Figure 
6.1-1. 
Figure 6.1-1 Criteria for Dose Finding and Expansion 
Enter 3 subjects 
0 Subjects 
with DLT
1 Subject
with DLT
2  or 3 Subjects 
with DLT
If at Dose Level 1:
Open cohort expansion at 
Dose Level 1;
If at Optional Dose Level:
Open cohort expansion at 
Optional Dose Level
Enter 3 Subjects 
at the 
Same Dose
If at Dose Level 1: 
Enter 3 subjects at   
Optional Dose Level;
If at Optional Dose Level:
STOP 
1 of 6 Subjects with DLT
≥ 2 of 6 Subjects with DLT
If at Dose Level 1:
Enter 3 subjects at 
Optional Dose Level;
If at Optional Dose Level:
STOP 
If at Dose Level 1: 
Open cohort expansion
at Dose Level 1;
If at Optional Dose Level:
Open cohort expansion 
at Optional Dose Level.
 
See Table 6.1.1-1 for dose levels. DLT=dose-limiting toxicity. 
 
6.1.2.1 
Definition of Dose-limiting Toxicity  
A DLT is defined as the occurrence of any of the following toxicities that are considered 
related to IMP, with onset from the first dose to 14 days after the last dose of IMP in 
Cycle 1:  
Hematologic Toxicity 
1) Grade 3 thrombocytopenia with clinically significant bleeding; 
2) Grade 4 thrombocytopenia; 
3) Febrile neutropenia (absolute neutrophil count < 500/mm3 with a single temperature 
of > 38.3°C [101°F]); 

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4) Grade 4 neutropenia of duration > 7 days; 
Note: Grade > 3 lymphopenia or leukopenia of any duration is not considered a DLT. 
Non-hematologic Toxicity 
5) Aspartate transaminase (AST) or alanine transaminase (ALT) elevation > 5 to 
≤ 10 times the upper limit of normal (ULN) (Grade 3) that does not downgrade to 
≤ Grade 1 (or to baseline grade if  > Grade 1 at baseline) within 14 days; 
6) AST or ALT elevation > 10 times ULN; 
7) Total bilirubin > 5 times ULN; 
8) ALT or AST elevation > 3 times ULN AND concomitant total bilirubin > 2 times 
ULN, without initial findings of cholestasis (elevated serum alkaline phosphatase), 
AND no other immediately apparent possible causes of ALT/AST elevation and 
hyperbilirubinemia, including, but not limited to, tumor progression, viral hepatitis, 
pre-existing chronic or acute liver disease, or the administration of other drug(s) 
known to be hepatotoxic; 
9) A ≥ Grade 3 non-hematologic laboratory AE (other than AST, ALT, or bilirubin) is a 
DLT only if it requires medical intervention or hospitalization. Exception: Grade 3 or 
Grade 4 electrolyte abnormalities that are not associated with clinical signs or 
symptoms, and either resolve spontaneously or respond to conventional medical 
intervention are not DLTs; 
Note: ≥ Grade 3 elevation of amylase and/or lipase of any duration not associated 
with clinical or radiographic evidence of pancreatitis is not a DLT; 
10) Grade 4 non-hematologic non-laboratory AE; 
11) Grade 3 skin rash that does not improve to ≤ Grade 2 within 3 days of initiation of 
maximal supportive care; 
12) Grade 3 uveitis, bronchospasm, or neurologic toxicity of any duration; 
13) Any other Grade 3 non-hematologic non-laboratory AE lasting > 7 days, with the 
following exceptions: 
a) Grade 3 inflammatory reaction attributed to a local antitumor response (e.g., 
inflammatory reaction at sites of metastatic disease, lymph nodes, tumor lysis 
syndrome) is not a DLT; 
b) Grade 3 fatigue is not a DLT; 
c) Grade 3 fever not associated with hemodynamic compromise is not a DLT; 
14) Grade 2 or higher pneumonitis of any duration; 
15) Any Grade 2 uveitis, eye pain, or blurred vision that does not respond to topical 
therapy and does not improve to Grade 1 within 14 days OR requires systemic 
treatment. 

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6.1.2.2 
Definition of Maximum Tolerated Dose 
The MTD is defined as one dose level below the dose level of the cohort where ≥ one-third of 
the subjects experience DLT. 
6.1.3 
Phase 2: Expansion Cohort  
To further characterize the safety, tolerability, and anti-tumor activity of the combination, up 
to 184 subjects (21 to 36 subjects per tumor type) with locally advanced or metastatic disease 
in the following tumor types will be enrolled: squamous cell NSCLC; PD-L1-non-expressing 
non-squamous cell NSCLC; SCCHN; colorectal carcinoma, non-microsatellite instability 
(non-MSI) high; hepatocellular carcinoma (HCC), pancreatic adenocarcinoma, and ovarian 
cancer (including primary peritoneal cancer and fallopian tube carcinoma). Subjects will be 
treated with the highest dose of the combination regimen that was considered tolerable in 
Phase 1.  
The SRC will review cumulative safety data from all subjects approximately every 2 months 
during the enrollment period. Clinical safety in the expansion cohorts will be monitored 
continually. If the rate of AEs meeting DLT definitions during the expansion portion of the 
study is > 1/3 in at least 3 evaluable subjects within a cohort, these findings will be discussed 
by the SRC, in the context of all available safety information, to determine whether 
enrollment to that cohort and/or the remaining cohorts should be suspended, whether a lower 
dose should be examined, or whether any additional monitoring or treatment requirements 
should be implemented. 
6.2 
Number of Subjects, and Numbers and Location of Investigative Sites 
Up to 188 subjects at up to 23 sites in the US will be enrolled in this clinical trial. Of these, 
4 subjects were enrolled in Phase 1 (dose-finding) and up to 184 subjects will be enrolled in 
Phase 2 (cohort-expansion). The actual size of the study will depend on the DLTs observed 
and the resultant number and sizes of the cohorts in Phase 1 of the trial. 
6.3 
Study Duration  
The study is composed of up to a 28-day Screening Period followed by a treatment period of 
up to 96 weeks from Cycle 1 Day 1. Subjects who stop treatment without disease progression 
and who experience disease progression within 12 months of their last dose of IMP may 
receive additional cycles, as described in Section 8.1.6. (NOTE: Upon implementation of 
Amendment 3, subjects who discontinued IMP without disease progression will not be 
allowed to receive additional IMP upon disease progression.)  Subjects who discontinue IMP 

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will enter a follow-up period and will be followed for survival. (Upon implementation of 
Amendment 3, survival follow-up will be discontinued for all subjects as described in 
Section 9.5.) 
7 
SELECTION AND WITHDRAWAL OF SUBJECTS 
7.1 
Procedures for Enrollment 
Interactive response technology (IRT) will be used to enroll subjects in the study. Instructions 
for using the IRT system will be described in the study procedure manual.   
7.2 
Inclusion Criteria 
Study populations for this study are: 
• 
Phase 1 dose finding: Adult subjects with locally advanced or metastatic solid tumors. 
• 
Phase 2 cohort expansion: Adult subjects with locally advanced or metastatic squamous 
cell NSCLC; PD-L1 non-expressing non-squamous cell NSCLC; SCCHN; colorectal 
carcinoma, non-MSI high; ovarian cancer (including primary peritoneal cancer and 
fallopian tube carcinoma); HCC; or pancreatic adenocarcinoma.  
Subjects must meet each one of the following inclusion criteria during the Screening period 
in order to be eligible for participation in the study. In addition, subjects participating in 
Phase 2 must meet all the inclusion criteria and have none of the exclusion criteria specified 
in Section 7.4. 
1) Subject is age 18 years or older; 
2) Subject must have histologically or cytologically confirmed solid tumor;   
3) Subject must have locally advanced or metastatic solid tumor; 
4) Subject has received appropriate cancer therapy as defined by: 
a) For subjects in Phase 1: Subject has no additional therapy options available 
known to prolong survival with the exception of PD-1 blockade (Subjects with 
tumors for which nivolumab has survival benefit who have not received PD-1 
blockade are eligible.) Prior therapy is not required for a subject with a tumor type 
that has no standard treatment regimen that is considered by the Investigator to be 
appropriate;  
OR subject meets prior therapy requirements for their tumor type provided 
below in the Additional Eligibility Criteria for Subjects in Phase 2; 
Note: Subjects in Phase 1 with NSCLC of non-squamous histology must be 
tested for epidermal growth factor receptor (EGFR) mutations and anaplastic 
lymphoma kinase (ALK) rearrangement. Subjects with EGFR activating 
mutations or ALK rearrangement must have progressed during or after, or been 
intolerant to, at least one prior approved EGFR or ALK targeted therapy; 

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b) For subjects in Phase 2, see prior therapy requirements provided below in the 
Additional Eligibility Criteria for Subjects in Phase 2; 
5) Subject has at least 1 measurable lesion per RECIST v. 1.1. Note: Lesions located in a 
previously irradiated field must have subsequent radiographic disease progression in 
that site in order to be considered measurable; 
6) Subject has an Eastern Cooperative Oncology Group (ECOG) performance status 
(PS) of 0 or 1; 
7) If the subject is a woman of child-bearing potential or man who is sexually active 
with woman of child-bearing potential, the subject agrees to use adequate 
contraception from signing of the ICF, for the duration of study participation; and for 
23 weeks after the last dose of IMP for women or 31 weeks after the last dose of IMP 
for men; 
8) Subject must have adequate hematological, renal, hepatic and respiratory functions 
defined below: 
a) White blood cells ≥ 2.0 × 109/L (2000/mm3); 
b) Absolute neutrophil count > 1.5 × 109/L (1500/mm3); 
c) Platelets > 90 × 109/L (90000/mm3), or > 60 × 109/L (60000/mm3) for subjects 
with hepatocellular carcinoma; 
d) Hemoglobin ≥ 9.0 g/dL (5.6 mmol/L); 
e) Serum total bilirubin ≤ 1.5 × ULN (except subjects with Gilbert syndrome or 
hepatocellular carcinoma, who can have serum total bilirubin < 3.0 mg/dL); 
f) AST and ALT ≤ 3 × ULN, or ≤ 5 × ULN for subjects with liver metastases or 
hepatocellular carcinoma; 
g) Serum creatinine ≤ 1.5 × ULN OR calculated creatinine clearance (CrCL) 
≥ 40 mL/min (using the Cockcroft-Gault formula) 
Female CrCL = (140-age in years) × weight in kg × 0.85 
 
 
                          72 × serum creatinine in mg/dL 
Male CrCL = (140-age in years) × weight in kg × 1.00 
 
 
                        72 × serum creatinine in mg/dL; 
9) The subject is willing to undergo tumor biopsy during the Screening period, or if the 
tumor is inaccessible for biopsy, archived tumor material must be available for 
submission; 
10) The subject is able to understand and willing to sign the ICF. 
7.3 
Exclusion Criteria 
Subjects will not be eligible to participate in this study if any one of the following exclusion 
criteria is met during the Screening period. In addition, subjects participating in Phase 2 must 
meet all the inclusion criteria and have none of the exclusion criteria specified in Section 7.4. 

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1) Female subject who is pregnant or breast-feeding, or any subject expecting to 
conceive or father a child during this study; 
2) Subject has an uncontrolled intercurrent illness that in the opinion of the Investigator 
would compromise the safety of the subject. These may include, but are not limited to, 
uncontrolled infection, unstable angina, interstitial lung disease, or clinically 
significant cardiac arrhythmia; 
3) Subjects has psychiatric illness/social situations that in the opinion of the investigator 
would limit compliance with study requirements; 
4) Subject has primary central nervous system (CNS) tumor or known CNS metastases 
and/or history of CNS metastases and/or carcinomatous meningitis; Exception: 
Subjects are eligible if CNS metastases are adequately treated and subjects are 
neurologically returned to baseline (except for residual signs or symptoms related to 
the CNS treatment) for at least 4 weeks prior to enrollment. In addition, subjects must 
be off corticosteroids for 4 weeks prior to enrollment; 
5) Subject has received prior therapy for cancer or major surgery within 28 days, or 
42 days for nitrosourea or mitomycin C, prior to Cycle 1 Day 1, or 14 days for 
tamoxifen; 
6) Subject has received radiotherapy or radiosurgery within 14 days prior to Cycle 1 
Day 1; 
7) Subject has been previously treated with an anti-PD-1, anti-PD-L1, anti-PD-L2, 
anti-CD137, or anti-CTLA-4 antibody or any other antibody or drug specifically 
targeting T-cell co-stimulation or checkpoint pathways; 
8) Subject has been previously treated with mogamulizumab; 
9) Subject has a history of allergy or hypersensitivity to study drug components; 
10) Subject has received a live, attenuated vaccine within 28 days prior to Cycle 1 Day 1; 
11) Subject has a history of organ transplant or allogeneic bone marrow transplant; 
12) Subject has any unresolved toxicity Grade > 1 (defined by Common Terminology 
Criteria for Adverse Events version 4.03 [CTCAE v. 4.03]) from previous anti-cancer 
therapy, excluding alopecia, fatigue, and laboratory values listed in the inclusion 
criteria. Subjects with irreversible toxicity that is not reasonably expected to be 
exacerbated by the investigational product may be included (e.g., hearing loss) at the 
discretion of the Investigator; 
13) Subject use of immunosuppressive medication within 14 days before Cycle 1 Day 1. 
Note: Inhaled, ocular, intranasal, intra-articular, or topical corticosteroids are allowed. 
Non immunosuppressive doses of systemic steroids for adrenal replacement or for 
contrast allergy are allowed; 
14) Subject has an active autoimmune disease or a history of autoimmune disease which 
may affect vital organ function or require immune suppressive treatment including 
systemic corticosteroids; these include but are not limited to subjects with a history of 
immune-related neurologic disease, multiple sclerosis, uveitis, autoimmune 
(demyelinating) neuropathy, Guillain-Barré syndrome, myasthenia gravis; transverse 

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myelitis; systemic autoimmune disease such as systemic lupus erythematosus, 
connective tissue diseases, scleroderma, autoimmune hepatitis; 
a) Exceptions: Subject with vitiligo, alopecia, type I diabetes mellitus, and endocrine 
deficiencies including hypothyroidism managed with replacement hormones 
including physiologic corticosteroids are eligible. Subject with psoriasis 
controlled with topical medication, or conditions not expected to recur in the 
absence of an external trigger (precipitating event) are eligible; 
15) Subject has a history of toxic epidermal necrolysis or Stevens-Johnson syndrome; 
16) Subject has a history of inflammatory bowel disease, Crohn’s disease, ulcerative 
colitis, or Wegener’s granulomatosis; 
17) Subject has primary or acquired immunodeficiency or known history of testing 
positive for human immunodeficiency virus (HIV) or known acquired 
immunodeficiency syndrome;  
18) Subject who tests positive for hepatitis B surface antigen (HBVsAg) or hepatitis C 
RNA indicating acute or chronic infection except for subjects with hepatocellular 
carcinoma; 
19) Subject has another active malignancy requiring concurrent intervention; 
20) Subject who is receiving any other investigational agents;  
21) Subject has another condition that, in the opinion of the Investigator and/or Sponsor, 
would interfere with evaluation of the IMP or interpretation of subject safety or study 
results; 
22) Subject has a history of pneumonitis or interstitial lung disease. 
7.4 
Additional Eligibility Criteria for Subjects in Phase 2 
In addition to having to meet all the inclusion criteria in Section 7.2 and to have none of the 
exclusion criteria in Section 7.3, subjects must meet all the following inclusion criteria and 
have none of the following exclusion criteria for the relevant tumor type during the Screening 
period in order to be eligible for participation in Phase 2 of the study. 
7.4.1 
Non-small-cell Lung Cancer 
7.4.1.1 
Non-small-cell Lung Cancer, Squamous Cell 
Inclusion Criteria: 
1) Subject has histologically or cytologically confirmed Stage IIIB or Stage IV 
(according to version 7 of the International Association for the Study of Lung Cancer 
Staging Manual in Thoracic Oncology; see Procedure Manual) squamous cell 
NSCLC; 

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2) Prior Therapy: Subject experienced disease recurrence or progression during or after 
platinum doublet-based chemotherapy for advanced or metastatic disease; 
a) Subject with recurrent or progressive disease within 6 months after completing 
platinum-based chemotherapy for local disease are eligible; 
b) Subject with recurrent or progressive disease > 6 months after 
platinum-containing adjuvant, neoadjuvant or definitive chemoradiation therapy 
given for local disease, who also subsequently progressed during or after a 
platinum doublet-based regimen given to treat the recurrence, are eligible. 
7.4.1.2 
Non-small-cell Lung Cancer, Nonsquamous, PD-L1 Non-expressing 
Inclusion Criteria: 
1) Subject has histologically or cytologically confirmed Stage IIIB or Stage IV 
(according to version 7 of the International Association for the Study of Lung Cancer 
Staging Manual in Thoracic Oncology; see Procedure Manual) non-squamous cell 
NSCLC; 
2) Subject’s tumor must be PD-L1 non-expressing on immunohistochemistry (IHC) 
testing performed by the central laboratory during the Screening period. Either a 
formalin-fixed, paraffin-embedded (FFPE) tissue block or tumor tissue sections must 
be submitted for biomarker evaluation during the Screening period. The tumor tissue 
sample may be fresh or archival. Tissue must be a core needle biopsy, excisional or 
incisional biopsy. Fine needle biopsies, drainage of pleural effusions with cytospins, 
or punch biopsies are not considered adequate for biomarker review. Biopsies of bone 
lesions that do not have a soft tissue component or decalcified bone tumor samples are 
also not acceptable; 
3) Prior Therapy: Subject experienced disease recurrence or progression during or after 
platinum doublet-based chemotherapy for advanced or metastatic disease; 
a) Subject with recurrent or progressive disease within 6 months after completing 
platinum-based chemotherapy for local disease are eligible; 
b) Subject with recurrent or progressive disease > 6 months after platinum-
containing adjuvant, neoadjuvant or definitive chemoradiation therapy given for 
local disease, who also subsequently progressed during or after a platinum 
doublet-based regimen given to treat the recurrence, are eligible; 
c) Subjects must be tested for EGFR mutations and ALK rearrangement. Subjects 
with EGFR activating mutations or ALK rearrangement must have progressed 
during or after, or been intolerant to, at least one prior approved EGFR or ALK 
targeted therapy. 

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7.4.2 
Squamous Cell Carcinoma of Head and Neck 
Inclusion Criteria: 
1) Histologically confirmed squamous cell carcinoma of oral cavity, pharynx, or larynx; 
Squamous cell carcinoma of unknown primary is allowed only if tumor is HPV16 
positive; 
2) Stage III or IV and not amenable to local therapy with curative intent (surgery or 
radiation therapy with or without chemotherapy); 
3) Prior Therapy: Tumor progression or recurrence within 6 months of last dose of 
platinum therapy in the adjuvant (i.e., with radiation after surgery), primary (i.e., with 
radiation), recurrent, or metastatic setting. Clinical progression after platinum therapy 
is an allowable event for entry and is defined as progression of a lesion at least 10 mm 
in size that is amenable to caliper measurement (e.g., superficial skin lesion as per 
RECIST v 1.1) or a lesion that has been visualized and photographically recorded 
with measurements and shown to have progressed. 
Exclusion Criteria: 
1) Histologically confirmed recurrent or metastatic carcinoma of the nasopharynx or 
salivary gland; 
2) Subject with base of skull lesion(s) with possible dural or brain parenchymal 
involvement that may require local therapy e.g. radiation; 
3) Non-squamous histologies (e.g., mucosal melanoma); 
7.4.3 
Colorectal Carcinoma, non-Microsatellite Instability High 
Inclusion Criteria: 
1) Subject has histologically confirmed metastatic or recurrent colorectal carcinoma; 
2) Microsatellite instability status low (MSI-L) or microsatellite stable (MSS) as 
detected by an accredited laboratory per local procedures see Section 9.2.7.1. 
3) Prior treatment: Progression during, after, or been intolerant following the last 
administration of approved standard therapies, which must include at minimum a 
fluoropyrimidine, oxaliplatin, and irinotecan, as well as at least one of the following 
agents, if approved or in standard national guidelines, bevacizumab, cetuximab or 
panitumumab (if KRAS wild type), or regorafenib. 
Exclusion Criterion: 
1) Microsatellite instability-high (MSI-H) tumor status detected by an accredited 
laboratory per local procedures. 

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7.4.4 
Ovarian Cancer 
Inclusion Criteria: 
1) Female subjects with International Federation of Gynecology and Obstetrics Stage Ic, 
Stage II, Stage III, Stage IV, recurrent, or persistent (unresectable) histologically 
confirmed epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube 
carcinoma; 
2) Subjects are allowed to have received up to 4 prior cytotoxic regimens for treatment 
of their epithelial ovarian, fallopian tube, or primary peritoneal cancer; they must have 
had one prior platinum-based chemotherapeutic regimen for management of primary 
disease, possibly including intra-peritoneal therapy, consolidation, biologic/targeted 
(non-cytotoxic) agents (e.g., bevacizumab) or extended therapy administered after 
surgical or non-surgical assessment; subjects are allowed to have received, but are not 
required to have received, 1 to 2 cytotoxic regimens for management of recurrent or 
persistent disease; (for the purposes of this study, poly-adenosine diphosphate (ADP) 
ribose polymerase (PARP) inhibitors given for recurrent or progressive disease will 
be considered cytotoxic); if 2 cytotoxic regimens had been received for management 
of recurrent or persistent disease, one of these regimens would have had to contain 
either a platinum or taxane agent; 
Platinum-free Interval - subjects must have progressed < 6 months after completion of 
their last platinum-based chemotherapy; 
3) Albumin greater than or equal to 2.8 g/dL. 
Exclusion Criterion: 
1) Subject has mucinous histology. 
7.4.5 
Hepatocellular Carcinoma 
Inclusion Criteria: 
1) Histologically confirmed hepatocellular carcinoma not amenable for management 
with curative intent by surgery or local therapeutic measure; 
2) Subject must have received sorafenib treatment and either:  
• 
have had documented radiographic or symptomatic progression during or after 
sorafenib therapy; OR 
• 
be intolerant of sorafenib (defined as Grade 2 drug-related adverse event which 1) 
persisted in spite of comprehensive supportive therapy according to institutional 
standards AND 2) persisted or recurred after sorafenib treatment interruption of at 
least 7 days and dose reduction by one dose level (to 400 mg once daily) 
AND/OR Grade 3 drug-related adverse event which 1) persisted in spite of 
comprehensive supportive therapy according to institutional standards OR 2) 
persisted or recurred after sorafenib treatment interruption of at least 7 days and 
dose reduction by one dose level (to 400 mg once daily);  

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OR must have documented refusal of sorafenib; 
3) Subject has Child-Pugh score of ≤6, i.e., Child-Pugh A (Appendix 2); 
4) INR ≤ 2.3 or Prothrombin time (PT) ≤ 6 seconds above control; 
5) Subject has HBV DNA viral load undetectable or < 100 IU/mL at screening.  If 
subject has detectable HBsAg, HBeAg, or HBV DNA (indicating ongoing viral 
replication of hepatitis B, he/she must be on antiviral therapy per regional standard of 
care guidelines prior to initiation of study therapy. If not on antiviral therapy at 
screening, then the subject must initiate treatment per regional standard of care 
guidelines prior to C1D1 and must be willing to continue antiviral therapy while on 
study treatment. 
Exclusion Criterion: 
1) Any history of hepatic encephalopathy 
2) Any prior (within 1 year) or current clinically significant ascites as measured by 
physical examination and that requires paracentesis for control; 
3) Active coinfection with both hepatitis B (i.e., HBVsAg and/or hepatitis B DNA) and 
hepatitis C (i.e., hepatitic C RNA) 
4) Hepatitis D infection in subjects with hepatitis B 
5) Any history of clinically meaningful variceal bleeding within the last three months. 
7.4.6 
Pancreatic Adenocarcinoma 
Inclusion Criteria: 
1) Subject has histologically or cytologically confirmed locally advanced unresectable or 
metastatic pancreatic ductal adenocarcinoma; 
2) Tumor sample available for MSI testing (Note: archived material is sufficient); 
3) Prior treatment: Subject must have received at least one prior chemotherapy regimen 
for their disease and must have radiological or clinical progression or documented 
unacceptable toxicity. 
Exclusion Criterion: 
1) Known microsatellite instability-high (MSI-H) tumor status. 
7.5 
Removal of Subjects from Therapy or Assessment 
A subject is free to withdraw his/her consent and discontinue study treatment or participation 
in the study at any time for any reason. A subject may also be discontinued from the 
treatment, at the discretion of the Investigator and/or sponsor, for any of the following 
reasons:  
• 
Withdrawal of consent from further treatment with IMP; 

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• 
Withdrawal of consent from the study; 
• 
AEs (see Section 10.3); 
• 
Required use of prohibited concomitant medications; 
• 
Non-compliance that, in the opinion of the Investigator or Sponsor, warrants withdrawal 
(e.g., refusal to adhere to scheduled visits); 
• 
Major protocol violation; 
• 
It is not considered in the best interest of the subject to continue; 
• 
Pregnancy; 
• 
Subjects who have unequivocal documented disease progression or symptomatic disease 
progression and are not eligible for continued treatment (see Section 8.1.5); 
• 
Lost to follow-up; 
• 
Administrative reasons (e.g., termination of the study). 
The Investigator must maintain a record of all subjects who discontinue from the study prior 
to completion; the reason(s) for study discontinuation will be documented. In the event that a 
subject chooses to withdraw from the study, the Investigator should make a reasonable 
attempt to obtain and record the reason(s) for withdrawal, if possible, although the subject is 
not obligated to provide such a reason.  
If treatment is discontinued, both IMPs will be discontinued (e.g., subjects will not be 
allowed to continue one investigational agent if the other is discontinued). For any case of 
treatment discontinuation (whether or not the subject is at the clinical site), the Investigator 
should ask the subject to complete the End-of-Treatment (EOT) and Follow-up visit 
procedures, provided that the subject has not withdrawn consent for those procedures (see 
Table 9-1 and Table 9-2 for the Schedule of Assessments). Subjects withdrawn from study 
without unequivocal disease progression or withdrawal of consent for follow up should 
continue tumor assessments until a new anticancer therapy is started, unequivocal disease 
progression is documented, withdrawal of consent for the follow-up contacts, or death.  
If a subject refuses to complete EOT procedures and/or the Follow-up visit, this refusal will 
be recorded. Subjects will be considered lost to follow-up only if no contact has been 
established by the time the study is completed such that there is insufficient information to 
determine the subject’s status at that time. Subjects who refuse continuing participation in the 
study, including telephone contacts, should be documented as “withdrawal of consent” rather 
than “lost to follow-up.” Investigators should document attempts to re-establish contact with 
unresponsive subjects throughout the study period. If contact with a missing subject is re-
established, the subject should not be considered lost to follow-up and any evaluations should 
resume according to the protocol. 

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Procedures to be followed for subjects who are ongoing in the study (i.e., subjects who are 
continuing to receive study treatment or who are in safety or survival follow-up) at the time 
of data cutoff for completion of analyses are described in Section 9.5.  
The Sponsor reserves the right to terminate the study at any time. 
7.5.1 
Replacement of Subjects  
Subjects in Phase 1 will be considered nonevaluable for DLT and will be replaced if they do 
not experience a DLT and:  
• 
they do not receive all infusions of both IMPs in Cycle 1 within 28 days at the doses 
assigned to the cohort in which they are enrolled, or 
• 
they do not complete the safety follow-up through the end of the DLT evaluation period 
(Section 6.1.2.1).  
Subjects enrolled in Phase 2 may be replaced, for these same reasons, at the discretion of the 
Sponsor. 
8 
TREATMENTS 
8.1 
Identity of Investigational Medicinal Products 
The Sponsor will provide both IMPs (mogamulizumab and nivolumab) to the investigational 
sites. Information about the IMPs to be used in the trial is summarized in Table 8.1-1 
Table 8.1-1 Identification of Investigational Medicinal Products 
Investigational 
Medicinal Product 
Product Manufacturer 
Concentration and Formulation as Supplied 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
iv=intravenous; USP=United States Pharmacopeia. 
  

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All IMPs will be labelled in an open-label fashion. Labels will bear the appropriate text as 
required by local regulatory requirements. 
 
 
Guidance on the dilution procedures and recommended storage conditions for the diluted 
solutions of the IMPs can be found in the Pharmacy Manual.   
Upon completion or termination of the study, all unopened containers of IMP must be 
destroyed at the site according to applicable regulations, institutional guidelines, and 
procedures, unless other arrangements have been approved by the Sponsor. 
8.1.1 
Treatments to be Administered 
The dose levels of the IMPs during the Phase 1 are described in Table 6.1.1-1. The dosing 
schedules of the IMPs during the study are described in Table 8.1.1-1. 
Table 8.1.1-1 Dosing Schedules of Mogamulizumab and Nivolumab During Phase 1 and 
Phase 2 
 
Cycle 1 
Cycle ≥2 
 
Day 1 
Day 8 
Day 15 
Day 22 
Day 1 
Day 15 
Nivolumab 
X 
 
X 
 
X 
X 
Mogamulizumab 
X 
X 
X 
X 
X 
X 
 
Treatments will be administered on an outpatient basis. Each dose of IMP will be prepared by 
the pharmacy (refer to the Pharmacy Manual for full preparation, administration, and storage 
requirements). Mogamulizumab dosing calculations should be based on the body weight 
assessed at Cycle 1 Day 1 (baseline). Mogamulizumab dose adjustments for each cycle are 
required for greater than a 10% change in body weight.  
All subjects will receive 240 mg of nivolumab as at least a 30-minute iv infusion on Days 1 
and 15 of each 28-day cycle. When both nivolumab and mogamulizumab are administered at 
the same visit, the infusion of mogamulizumab will be started at least 30 minutes after the 
end of infusion of nivolumab.  
• 
Nivolumab injection is to be administered as an iv infusion through a 0.2-micron to 
1.2-micron pore size, low-protein binding polyethersulfone membrane in-line filter 
• 
Subjects may be dosed no less than 12 days from the previous dose of nivolumab.  
• 
There are no premedications recommended for nivolumab prior to the first infusion. 

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• 
Subjects should be carefully monitored for infusion-related reactions during IMP 
administration. If an acute infusion-related reaction is noted, subjects should be managed 
according to Section 8.2.2. 
Subjects will then receive the cohort-assigned dose of mogamulizumab as at least a 1-hour iv 
infusion on Days 1, 8, 15, and 22 of the first cycle and on Days 1 and 15 of subsequent 
cycles.  
• 
Mogamulizumab injection dose is to be administered as an iv infusion through a 0.22- or 
0.2-μm in-line filter.   
• 
Subjects may be dosed no less than 5 days from the previous dose of mogamulizumab.  
• 
Premedication with acetaminophen orally and diphenhydramine 50 mg iv (or equivalent) 
is recommended before the first mogamulizumab infusion (see Section 8.2.1).  
• 
Subjects should be carefully monitored for infusion-related reactions during IMP 
administration. If an acute infusion-related reaction is noted, subjects should be managed 
according to Section 8.2.2. 
Subjects should be closely monitored for AEs for at least: 
• 
30 minutes after the completion of the nivolumab infusion; 
• 
4 hours after the completion of the mogamulizumab infusion for the first 2 combination 
infusions (i.e., Cycle 1, Days 1 and 15); and  
• 
30 minutes after all other mogamulizumab infusions. 
8.1.2 
Dose Reduction and Dose Delay 
Doses of IMPs may be interrupted, delayed, or discontinued depending on how well the 
subject tolerates the treatment.  
8.1.2.1 
Dose Reduction 
There will be no intra-patient dose reduction of either IMP by the Investigator. Doses within 
an assigned cohort may only be changed at the discretion of the SRC. (As of Amendment 3, 
the SRC will be disbanded.) 
8.1.2.2 
Dose-delay Criteria 
IMP administration should be delayed for the following: 
• 
Any Grade 2 or 3 IMP-related AE, with the following exceptions: 
– Grade 2 IMP-related fatigue or laboratory abnormalities do not require a treatment 
delay. 
• 
Any Grade 3 IMP-related laboratory abnormality, with the following exceptions for 
lymphopenia or leukopenia, AST, ALT or total bilirubin or asymptomatic amylase or 
lipase: 

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– Lymphopenia or leukopenia of any grade does not require dose delay. 
– If a subject has a baseline AST, ALT or total bilirubin that is within normal limits, 
delay dosing for drug-related Grade ≥ 2 toxicity. 
– If a subject has baseline AST, ALT or total bilirubin within the Grade 1 toxicity 
range, delay dosing for IMP-related Grade ≥ 3 toxicity. 
– If a subject has baseline AST, ALT, or total bilirubin within the Grade 2 toxicity 
range, delay dosing for IMP-related toxicity that increase by 2-fold or values 
> 8 × ULN. 
– Any Grade ≥ 3 IMP-related amylase or lipase abnormality that is not associated with 
symptoms or clinical manifestations of pancreatitis does not require dose delay. The 
Medical Monitor should be consulted for such Grade ≥ 3 amylase or lipase 
abnormalities. (As of Amendment 3, decisions regarding subject treatment should be 
made according to site standard of care as determined by the Principal Investigator.) 
– Any AE, laboratory abnormality, or intercurrent illness which, in the judgment of the 
Investigator, warrants delaying the dose of study medication. 
Subjects who require delay of IMP should be re-evaluated weekly or more frequently if 
clinically indicated and resume IMP dosing when re-dosing criteria are met. 
8.1.3 
Criteria to Resume Dosing 
Subjects may resume treatment with IMP when the drug-related AE(s) resolve(s) to 
Grade ≤ 1 or baseline, with the following exceptions: 
• 
Subjects may resume treatment in the presence of Grade 2 fatigue. 
• 
Subjects who have experienced Grade 3 drug-related skin AE must have improvement to 
Grade ≤ 2 within 3 days. Treatment may resume once the AE has improved to Grade ≤ 1. 
• 
Subjects who have experienced a Grade 2 drug-related skin AE may resume treatment 
when it has resolved to Grade ≤ 1.  
• 
Subjects with baseline Grade 1 AST/ALT or total bilirubin who require dose delays for 
reasons other than a 2-grade shift in AST/ALT or total bilirubin may resume treatment in 
the presence of Grade 2 AST/ALT OR total bilirubin. 
– Subjects with combined Grade 2 AST/ALT AND total bilirubin values meeting 
discontinuation parameters should have treatment permanently discontinued. 
• 
Drug-related pulmonary toxicity must have resolved to baseline before treatment is 
resumed. Subjects with persistent Grade 1 pneumonitis (asymptomatic; clinical or 
diagnostic observations only, intervention not indicated) after completion of a steroid 
taper over at least 1 month may be eligible for retreatment if discussed with the Medical 
Monitor.  (As of Amendment 3, decisions regarding subject treatment should be made 
according to site standard of care as determined by the Principal Investigator.) 
• 
Drug-related endocrinopathies adequately controlled with only physiologic hormone 
replacement may resume treatment. 

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Dose delay of IMP for drug-related toxicity which results in treatment interruption of 
> 6 weeks requires treatment discontinuation, with the following exception: 
• 
Dosing delays of > 6 weeks for prolonged steroid tapers to manage drug-related AEs are 
allowed. Re-initiation of treatment in a subject with a dosing delay lasting > 6 weeks from 
the previous dose requires consultation with the Medical Monitor. (As of Amendment 3, 
decisions regarding subject treatment should be made according to site standard of care as 
determined by the Principal Investigator.)  Required protocol assessments should 
continue as per protocol even if dosing is delayed. Periodic study visits to assess safety 
and laboratory studies should also continue every 6 weeks or more frequently, if clinically 
indicated, during such dosing delays. 
8.1.4 
Criteria for Treatment Discontinuation for Toxicity 
IMP treatment should be permanently discontinued if one or more of the following drug-
related adverse events occurs: 
• 
Any AE occurring at any time during treatment that is related to IMP and that meets the 
DLT criteria listed in Section 6.1.2.1, with the following exceptions: 
– Grade 2 pneumonitis which was treated and resolved according to the management 
guidelines in Section 8.2.3. 
– Grade 3 or 4 drug-related endocrinopathy AEs, such as adrenal insufficiency, 
adrenocorticotropic hormone (ACTH) deficiency, hyper- or hypothyroidism, or 
glucose intolerance, which resolve or are adequately controlled with physiologic 
hormone replacement (corticosteroids, thyroid hormones) or glucose-controlling 
agents, respectively, may not require discontinuation after discussion with the 
Medical Monitor.  (As of Amendment 3, decisions regarding subject treatment should 
be made according to site standard of care as determined by the Principal 
Investigator.) 
• 
Grade ≥ 3 hypersensitivity reaction or infusion-related reaction  
• 
Any drug-related event that leads to delay in dosing lasting > 6 weeks from the previous 
dose requires discontinuation with the following exception:  
– Dosing delays of > 6 weeks for prolonged steroid tapers to manage drug-related AEs 
are allowed.  
– Re-initiation of treatment in a subject with a dosing delay lasting > 6 weeks from the 
previous dose requires consultation with the Medical Monitor. (As of Amendment 3, 
decisions regarding subject treatment should be made according to site standard of 
care as determined by the Principal Investigator.)  Required protocol assessments 
should continue as per protocol even if dosing is delayed. Periodic study visits to 
assess safety and laboratory studies should also continue every 6 weeks or more 
frequently, if clinically indicated, during such dosing delays. 
• 
Any AE, laboratory abnormality, or intercurrent illness which, in the judgment of the 
Investigator, presents a substantial clinical risk to the subject with continued IMP dosing. 

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8.1.5 
Treatment Beyond Disease Progression 
The IMPs used in this trial are meant to induce an immune response against the subject’s 
tumor and may not have an immediate effect on the tumor. In addition, the expected 
mechanism of action involves an infiltration of T-cells and inflammatory cells and local 
release of inflammatory cytokines. Therefore it is expected that initial radiographic 
progression may not be indicative of subsequent lack of response. Treatment may continue in 
spite of early radiographic progression, including appearance of new lesions, in the absence 
of symptomatic progression as long as the subject meets the other criteria in Sections 8.1.2 
and 8.1.3 and has not had an AE that meets the criteria for treatment discontinuation in 
Section 8.1.4. Treatment past initial RECIST-defined radiographic progression may continue 
according to Investigator judgment, in consultation with the Medical Monitor, based on the 
subject’s overall clinical status, overall tumor burden, and rate of progression, taking into 
account the subject’s other treatment options and need for urgent intervention. (As of 
Amendment 3, decisions regarding subject treatment should be made according to site 
standard of care as determined by the Principal Investigator.)  For example, a subject may 
continue treatment if a tumor assessment shows improvement or stable disease compared to 
the previous scan, even if there is progression compared to the baseline scan. Investigators 
may schedule an additional tumor assessment within 6 weeks after a scan showing 
progression, in order to reassess the subject’s response.   
Subjects may be treated after progression if they meet these criteria: 
• 
Investigator-assessed potential clinical benefit; 
• 
No disease-related clinical deterioration; 
• 
Absence of progressive tumor at critical anatomical sites (e.g., cord compression) 
requiring urgent alternative medical intervention; 
• 
Subject meets other re-dosing criteria in Section 8.1.3 and has not had an AE that meets 
the criteria for treatment discontinuation in Section 8.1.4. 
If treatment is continued in spite of radiographic progression, the Investigator should record 
the rationale, and the subject must be informed that treatment beyond initial progression is 
not standard of care, and the Investigator should discuss potential risks and alternative 
treatment options. The sponsor will provide a consent form for re-consent of the subject prior 
to continuation of dosing, subject to institutional review board (IRB) approval. 
Subjects should permanently discontinue study therapy upon evidence of further progression, 
defined as an additional 20% or greater increase in total measured tumor burden (TMTB) 
from time of initial progression. Total measured tumor burden should be determined as 
described in Section 9.2.6. The total measured tumor burden from time of initial progression 

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should be used as the reference baseline for comparison with the post-progression 
assessment.   
8.1.6 
Re-treatment for Progression during Follow-up 
Subjects who stop IMP without disease progression and who experience disease progression 
within 12 months of their last dose of IMP may receive additional IMP for up to 48 weeks 
provided that they meet the criteria in Sections 8.1.2, 8.1.3 and 8.1.4 and have not received 
other systemic therapy for their cancer. Biopsy of a progressing lesion should be obtained, if 
feasible. The Medical Monitor must be consulted before a subject in follow-up begins re-
treatment. Subject must be re-consented prior to restarting IMP. (Upon implementation of 
Amendment 3, subjects who discontinued IMP without disease progression will not be 
allowed to receive additional IMP upon disease progression.) 
The schedule of assessments for Cycle ≥ 3 should be followed, except that PK, PD, and 
anti-drug antibody (ADA) assessments are not required. 
8.2 
Management of Infusion-related Reaction and Other Toxicity 
8.2.1 
Premedication 
It is recommended that subjects be premedicated with acetaminophen orally and 
diphenhydramine 50 mg iv (or equivalent), before the first mogamulizumab infusion. If a 
subject experiences an infusion-related reaction at any time during the study, pre-medication 
is recommended prior to subsequent infusions (see Section 8.2.2). 
No premedications are recommended for nivolumab prior to first infusion. If a subject 
experiences an infusion-related reaction at any time during the study, pre-medication is 
recommended prior to subsequent infusions (see Section 8.2.2). 
8.2.2 
Treatment of Infusion-related Reactions 
As with any antibody, infusion-related reactions are possible. Appropriate drugs and medical 
equipment to treat allergic or anaphylactic reactions must be immediately available, and study 
personnel must be trained to recognize and treat infusion-related reactions. If a subject 
experiences an infusion-related reaction at any time during the study, premedication with the 
following medications is recommended prior to subsequent infusions: diphenhydramine 
50 mg (or equivalent) and/or acetaminophen 325 to 1000 mg at least 30 minutes before 
additional IMP administration. 

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All Grade 3 or 4 infusion-related reaction should be reported within 24 hours to the 
Sponsor (see Section 10.3.3.3). 
Treatment recommendations for infusion-related reactions are provided in Table 8.2.2-1 and 
may be modified based on local treatment standards or guidelines, as appropriate. If a subject 
has an infusion-related reaction, blood samples should be drawn for assessment of cytokines 
(Table 10.2-1). 
Cytokine-release syndrome is not expected with mogamulizumab or nivolumab, but if 
cytokine-release syndrome is suspected, consider use of cytokine antagonists such as 
tocilizumab (IL-6 receptor antagonist). 
Table 8.2.2-1 Recommended Management of Infusion-related Reaction 
Grade 
Symptoms 
Recommended Management 
1/2 
• Mild or Moderate (e.g., rash, flushing, 
urticaria, dyspnea, fever, pruritus/ 
itching, rigors/chills, sweating 
[diaphoresis], tachycardia) 
• Moderate reactions may require therapy 
but respond promptly to symptomatic 
treatment (e.g., antihistamines, NSAIDS, 
narcotics, corticosteroids, 
bronchodilators, iv fluids) 
•
The infusion rate of the IMP(s) should be 
temporarily interrupted until resolution of the event. 
• Acetaminophen, NSAIDS, antihistamines, 
narcotics, corticosteroids, bronchodilators, and iv 
fluids may be administered at the discretion of the 
Investigator.  
• The infusion should not be restarted until symptoms 
have subsided to Grade 1 or less.  
• The infusion may be re-started at half-rate when 
symptoms resolve. If no further complications 
ensue after 30 minutes, the rate may be increased 
full rate. If symptoms recur, then no further IMP 
should be administered at that visit.  
• Pre-medication prior to subsequent doses are 
recommended 
3/4 
• Severe/Life-threatening: Prolonged 
(i.e., not rapidly responsive to 
symptomatic medication and/or brief 
interruption of infusion); recurrence of 
symptoms following initial 
improvement; hospitalization indicated 
for other clinical sequelae (e.g., renal 
impairment, pulmonary infiltrates);  
• Pressor or ventilatory support indicated 
(i.e., bronchospasm, stridor, hypoxia, 
angioedema, swelling of lips, tongue, 
uvula, hypotension, abdominal pain, 
vomiting, hypoxia, syncope, collapse, 
incontinence). 
•
Halt infusion immediately. 
• Begin iv infusion of normal saline. 
• Initiate treatment according to institutional standard 
of care including corticosteroids, epinephrine, 
cytokine antagonists, bronchodilators, intubation 
and respiratory support, iv hydration and 
vasopressors. 
• Discontinue IMPs.   
IMP=investigational medicinal product; iv=intravenous; NSAIDS=non-steroidal anti-inflammatory drugs. 

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8.2.3 
Immune-associated Select Adverse Events of Interest 
Immuno-oncology agents are associated with AEs that can differ in severity and duration 
than AEs caused by other therapeutic classes. Nivolumab and mogamulizumab are 
considered immuno-oncology agents in this protocol. Early recognition and management of 
AEs associated with immuno-oncology agents may mitigate severe toxicity.  
Management algorithms have been developed to assist Investigators in assessing and 
managing the following groups of AEs and are included in the nivolumab IB: 
• 
Gastrointestinal 
• 
Renal 
• 
Pulmonary 
• 
Hepatic 
• 
Endocrinopathies 
• 
Skin 
• 
Neurological 
Recommended guidelines for managing hepatic events in subjects with elevated baseline 
LFTs are provided in Section 8.2.3.1. 
For treatment of skin toxicity, recommended treatment guidelines are provided in Table 
8.2.3-1.  

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Table 8.2.3-1 Recommended Management of Investigational Medicinal 
Product-related Dermatologic Toxicity 
Grade 
Dermatologic AE 
1 
Dosing delay is not required.  
• 
Initiate symptomatic therapy, e.g., antihistamines, topical or systemic corticosteroids 
(0.5 to 1.0 mg/kg/day methylprednisolone iv or oral, or equivalent), as needed.  
If persists > 2 weeks, or recurs: 
• 
Consider skin biopsya; 
• 
Consider 0.5 to 1.0 mg/kg/day methylprednisolone iv or oral, or equivalent. 
2 
• 
Hold IMPs. 
• 
Initiate symptomatic therapy, e.g., antihistamines, topical or systemic corticosteroids 
(0.5 to 1.0 mg/kg/day methylprednisolone iv or oral, or equivalent), as needed;  
If persists > 2 weeks or recurs: 
• 
Perform skin biopsya; 
• 
Consider 0.5 to 1.0 mg/kg/day methylprednisolone iv or oral, or equivalent. Once 
improving, taper steroids over at least 1 month, consider prophylactic antibiotics for 
opportunistic infections, and resume IMP. 
3 
• 
Hold IMPs until resolution to ≤Grade 1 or baseline grade. 
• 
Discontinue IMP if does not resolve to ≤ Grade 2 within 3 days of the initiation of 
maximal supportive care. 
• 
Perform skin biopsya;  
• 
Dermatology consult; 
• 
1.0 to 2.0 mg/kg/day methylprednisolone iv or equivalent iv. Once improving, taper 
steroids over at least 1 month, consider prophylactic antibiotics for opportunistic 
infections, and resume IMP. 
4 
• 
Discontinue IMPs;
• 
Perform skin biopsya;  
• 
Dermatology consult; 
• 
1.0 to 2.0 mg/kg/day methylprednisolone iv or equivalent iv. Once improving, taper 
steroids over at least 1 month, consider prophylactic antibiotics for opportunistic 
infections. 
a: Skin biopsy may be submitted to central laboratory. 
AE=adverse event; IMP=investigational medicinal product; iv=intravenous. 
8.2.3.1 
Recommended Management of Hepatic Events in Subjects with HCC  
Subjects with advanced HCC generally have underlying cirrhosis with decreased hepatic 
function. They may also have a concomitant chronic viral infection. For the HCC cohort of 
this study, the upper limits for inclusion account for baseline liver dysfunction and allow 
enrollment of subjects with AST or ALT elevations within the CTCAE Grade 2 range. For 
these subjects, the following guidelines are provided: 
• 
Dose delay criteria for hepatic events are outlined in Section 8.1.2.2. If AST or ALT 
levels do not improve with a dose delay of 3 - 5 days or if the levels worsen, initiate 
steroid therapy at 0.5 - 2 mg/kg/day methylprednisolone or oral equivalent. 

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• 
For ALT or AST levels > 8 × ULN, initiate steroid therapy promptly at 1 - 2 
mg/kg/day methylprednisolone or oral equivalent. 
• 
For all subjects initiating steroids, consult the Medical Monitor within 24 hours after 
initiation of steroids. Gastroenterology consult is recommended. If AST or ALT 
levels do not improve within 3 - 5 days or the levels worsen after the start of steroid 
therapy, discuss with the Medical Monitor the possibility of adding mycophenolate 
mofetil at 1 g BID. (As of Amendment 3, decisions regarding subject treatment 
should be made according to site standard of care as determined by the Principal 
Investigator.) 
• 
Tapering of steroids can start once AST or ALT levels have declined by 1 CTCAE 
grade. Taper steroids slowly over no less than 1 month. 
• 
IMP may resume when AST or ALT have returned to near baseline unless the criteria 
for permanent discontinuation are reached (Sections 4.1.19 and 4.2). The Medical 
Monitor must be consulted prior to resuming IMP for all subjects who required 
steroid intervention. (As of Amendment 3, decisions regarding subject treatment 
should be made according to site standard of care as determined by the Principal 
Investigator.) 
• 
Discontinue IMP for any drug-related liver function test (LFT) abnormality that meets 
the following criteria: 
– AST or ALT > 10 × ULN for > 2 weeks, 
– AST or ALT > 15 × ULN irrespective of duration, 
– T. bilirubin > 8 × ULN irrespective of duration for subjects with elevated bilirubin 
at study entry or > 5 × ULN for those with normal T bilirubin at entry, 
– Concurrent AST or ALT > 3 × ULN and T. bilirubin > 5 × ULN for subjects 
entering treatment with a normal bilirubin and up to 8 × ULN for subjects entering 
treatment with elevated bilirubin. 
8.3 
Method of Assigning Subjects to Treatment Groups 
In Phase 1, subjects who meet the eligibility criteria will be enrolled in the dose level that is 
open to enrollment by the IRT system. In Phase 2, subjects will be enrolled into the cohort by 
tumor type by the IRT system.  
8.4 
Blinding/Unblinding 
This study is not blinded. 
8.5 
Concomitant Treatments 
Any medication(s), including those taken within 30 days prior to the first dose of IMPs, 
throughout treatment with IMP, until the 30-day follow-up visit after the last dose of IMP or 

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until start of new anticancer therapy (whichever occurs first), and anytime thereafter if used 
to treat IMP-related SAEs will be recorded.  
8.5.1 
Permitted Concomitant Medications 
Subjects may receive medications to treat pre-existing conditions, IMP-related AEs, or 
IMP-unrelated AEs.  
Subjects are permitted the use of topical, ocular, intra-articular, intranasal, and inhalational 
corticosteroids (with minimal systemic absorption). Adrenal replacement steroids are 
permitted. A brief (less than 3 weeks) course of corticosteroids for prophylaxis (e.g., contrast 
dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type 
hypersensitivity reaction caused by a contact allergen) is permitted. 
Immunosuppressive agents including steroids may be used to treat IMP-related AEs, as 
described in Section 8.2. 
Concomitant palliative and supportive care for disease-related symptoms (including 
bisphosphonates and RANK-L inhibitors) is allowed if initiated prior to the first dose of study 
therapy.  
The potential for overlapping toxicities with radiotherapy and the IMPs currently is not 
known. Therefore, palliative radiotherapy is not recommended while receiving IMPs. If 
palliative radiotherapy is required, then IMP should be withheld for at least 1 week before, 
during and 1 week after radiation. Subjects should be closely monitored for any potential 
toxicity during and after receiving radiotherapy, and AEs considered related to radiotherapy 
should resolve to Grade ≤ 1 prior to resuming IMP. Only non-target bone lesions without 
lung tissue included in the planned radiation field or CNS lesions may receive palliative 
radiotherapy while on study treatment.  
8.5.2 
Prohibited and/or Restricted Treatments 
While on study, subjects are not permitted to receive any additional experimental therapy or 
any therapy to treat the disease under study other than the IMP. Supportive therapy to manage 
symptoms or AEs is acceptable as noted in Section 8.5.1. 
The following medications are prohibited during the study unless utilized to treat an AE: 
• 
Immunosuppressive agents; 
• 
Immunosuppressive doses of systemic corticosteroids, except as stated in Section 8.5.1; 

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• 
Any concurrent anti-neoplastic therapy (i.e., chemotherapy, hormonal therapy, 
immunotherapy, extensive, non-palliative radiation therapy, or standard or investigational 
agents for treatment of cancer). 
Live-attenuated vaccines should not be administered during the treatment period and for at 
least 3 months after the last dose of IMP unless, according to the judgment of the Investigator 
in consultation with the Medical Monitor, the benefit of vaccination outweighs the 
hypothetical increased risk for an AE after vaccination. (As of Amendment 3, decisions 
regarding subject treatment should be made according to site standard of care as determined 
by the Principal Investigator.) 
8.5.3 
Contraception 
Women of childbearing potential must use method(s) of contraception from the time of 
signing of the ICF, for the duration of study participation, and for 23 weeks after the last dose 
of IMP. This is calculated as 5 half-lives of nivolumab (half-life up to 25 days) plus 30 days 
(duration of ovulatory cycle). Men who are sexually active with woman of child-bearing 
potential must use method(s) of contraception from the time of signing of the ICF, for the 
duration of study participation, and for 31 weeks after the last dose of IMP. This is calculated 
as 5 half-lives of nivolumab plus 90 days (duration of sperm turnover).  
During the screening period, the Investigator should review contraception methods and the 
time period that contraception must be followed with the subject. The individual methods of 
contraception for each subject (hormonal or barrier method of birth control; abstinence) 
should be determined in consultation with the Investigator. 
8.6 
Treatment Compliance 
Subjects are administered the IMP(s) under direct supervision of study personnel. 
9 
STUDY PROCEDURES 
All efficacy, PK/PD, immunogenicity, and safety measurements obtained during the course 
of the study are summarized in Table 9-1 and Table 10.2-1.  Procedures to be followed for 
subjects who are ongoing in the study (i.e., subjects who are continuing to receive study 
treatment or who are in safety or survival follow-up) at the time of data cutoff for completion 
of analyses are described in Section 9.5.  
 

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Table 9-1 Schedule of Events:  Screening and Treatment Periods 
Procedureh 
Referenced 
Section(s) 
of Protocol 
Screening 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
 
D1 
D8 
D15 
D22 
D1 
D15 
D1 
D15 
EOT 
(Section 
9.3) 
Visit Window (days) 
 
–28 to -1 
- 
±2 
±2 
±2 
- 
±3 
- 
±3 
Written Informed Consenta 
6.1 / 9.1 
X 
- 
Inclusion/Exclusion Criteria 
7.2 / 7.3 
X 
Medical History/ Demographics 
9.2.1 
X 
Height 
 
X 
Physical Examination, ECOG 
PS, and Body Weight 
9.2.5 
X 
X 
 
 
 
X 
 
X 
 
X 
Pulse Oximetry  
9.2.3 
X 
X 
X 
X 
X 
X 
X 
Vital Signs 
9.2.3 
X 
Xb 
Xc 
Xb 
Xc 
Xd 
Xd 
Xd 
Xd 
X 
12-lead ECG 
9.2.4 
X 
X 
X 
X 
X 
Hematology Profile 
9.2.2 
X 
Xe 
X 
X 
X 
Xe 
X 
Xe 
X 
X 
Serum Chemistry Profile 
9.2.2 
X 
Xe 
X 
X 
X 
Xe 
X 
Xe 
X 
X 
Coagulation Profile 
9.2.2 
X 
Xe 
Xe 
Xe 
X 
Thyroid Function Testing 
9.2.2 
X 
Xe 
Xe 
X 
Urinalysis 
9.2.2 
X 
X 
Serum Pregnancy Testing 
(WOCBP) 
9.2.2 
X 
 
 
 
 
 
 
 
 
X 
Urine Pregnancy Testing 
(WOCBP) 
9.2.2 
 
Xe 
 
 
 
Xe 
 
Xe 
 
 
Virus Testing  
9.2.2 
X 
Tumor Assessment, MRI or CT, 
including serum tumor markers, 
as applicable 
9.2.6 
X 
 
 
 
 
 
 
 
Xf 
X 
Tumor Biopsy 
9.2.7 
Xg 
Xg 

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Table 9-1 Schedule of Events:  Screening and Treatment Periods 
Procedureh 
Referenced 
Section(s) 
of Protocol 
Screening 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
 
D1 
D8 
D15 
D22 
D1 
D15 
D1 
D15 
EOT 
(Section 
9.3) 
Visit Window (days) 
 
–28 to -1 
- 
±2 
±2 
±2 
- 
±3 
- 
±3 
Pharmacokinetics 
10.2 
Refer to Table 10.2-1 
Anti-drug Antibody 
Pharmacodynamics 
Adverse Events 
10.3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior/Concomitant Medications 
8.5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Mogamulizumab 
Administration 
8.1.1 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Nivolumab Administration 
8.1.1 
X 
X 
X 
X 
X 
X 
a: Informed consent must be obtained prior to undergoing any study specific procedure that is not part of normal care. Data from procedures that were done as part of normal 
care may be used once the subject signs the ICF, provided they were done within the screening window. 
b: Pre-dose (up to 30 minutes before SOI); and EOI (±5 minutes) of nivolumab; predose (up to 30 min before) SOI, every 15 (± 5 minutes) during infusion; and EOI 
(± 5 minutes) of mogamulizumab; hourly during the 4-hour post-infusion observation period. 
c: Pre-dose (up to 30 minutes before SOI) of mogamulizumab, every 15 (± 5 minutes) during infusion, and EOI (± 5 minutes) of mogamulizumab, 30 minutes (± 5 minutes) 
after EOI of mogamulizumab. 
d: Pre-dose (up to 30 minutes before SOI); and EOI (± 5 minutes) of nivolumab; predose (up to 30 min before) SOI, every 15 (± 5 minutes) during infusion; and EOI 
(± 5 minutes) of mogamulizumab; 30 minutes (± 5 minutes) after EOI of mogamulizumab. 
e: Day 1 labs can be done up to 3 days prior to dosing. 
f: Tumor assessments by RECIST v. 1.1 will be performed at Screening, at Week 10, at least every 12 weeks thereafter until unequivocal disease progression or death.  
g: Required at Screening (except as indicated in the inclusion criteria) and at Week 10 (unless the tumor is inaccessible for biopsy). 
h: Procedures to be followed for subjects who are ongoing in the study (i.e., subjects who are continuing to receive study treatment or who are in safety or survival follow-up) 
at the time of data cutoff for completion of analyses are described in Section 9.5.  
CT=computed tomography; ECG=electrocardiogram; ECOG=Eastern Cooperative Oncology Group; EOI=end of infusion; EOT= End of Treatment; IMP=investigational 
medicinal product; MRI=magnetic resonance imaging; PS=performance status; RECIST=Response Evaluation Criteria in Solid Tumors; SOI=start of infusion; 
WOCBP=women of child-bearing potential. 

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Table 9-2 Schedule of Events:  Post-treatment Follow-up 
 
Referenced 
Section(s)  
of Protocol 
Post Last Dose of IMPs Follow-up 
Procedured 
30 Days 
Day 100-110 and  
at Least Every  
100 days Thereafter 
Visit Window (Days) 
 
± 5  
 
Serum Tumor Markers, as applicable 
9.2.6 
Xa 
Xa 
Tumor Assessment, MRI or CT 
9.2.7 
Xa 
Xa 
Adverse Events 
10.3 
Xb 
Xb 
Concomitant Medications 
8.5/ 9.2.1 
Xc 
Xc 
Survival Assessment, including Anticancer 
Therapies 
6.3 
X 
X 
a: Subjects who complete or discontinue treatment without disease progression will have tumor assessments collected at 
least every 12 weeks or per institutional standard of care until a new anti-cancer therapy is started, unequivocal disease 
progression is documented, or death. 
b: AEs will be collected until 100 days after the last dose of IMP.   
c: Concomitant medications usage will be collected until the 30-day follow-up visit after the last dose of IMP or until the 
start of new anticancer therapy (whichever occurs first), and anytime thereafter if used to treat IMP-related SAEs. 
d: Procedures to be followed for subjects who are ongoing in the study (i.e., subjects who are continuing to receive study 
treatment or who are in safety or survival follow-up) at the time of data cutoff for completion of analyses are described in 
Section 9.5.  
AE=adverse event; CT=computed tomography; IMP=investigational medicinal product; MRI=magnetic resonance imaging; 
SAE=serious adverse event. 
9.1 
Screening 
No study-specific procedures that are not part of normal care may be initiated prior to the 
subject signing the informed consent in compliance with International Committee on 
Harmonisation-Good Clinical Practices (ICH-GCP) and local legislation. Screening 
evaluations used to determine the subject’s study eligibility must be completed within 
28 days prior to starting treatment unless otherwise specified. Data from procedures that were 
done as part of normal care may be used once the subject signs the ICF, provided they were 
done within the screening window. 
At the Screening Visit, the Investigator will review the written ICF with each subject to 
ensure the understanding of the study and the study procedures. The subject, individual 
obtaining the ICF, will read, sign, and date/time the ICF and any other locally applicable 
documents. A photocopy of the signed ICF must be provided to the subject and the original 
document retained in the subjects source or study file. The date the screening procedures 
begin will be collected. 

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During the Screening period, the Investigator should review contraception methods and the 
time period that contraception must be followed. The individual methods of contraception for 
each subject (hormonal or barrier method of birth control; abstinence) should be determined 
in consultation with the Investigator. 
Refer to the study-specific procedure manual for information to be collected for screen 
failures. 
9.2 
Baseline and Treatment  
9.2.1 
Demographics, Medical History, Pre-treatment Adverse Events 
Subject demographics (race, ethnicity, gender), medical history, and current medical 
conditions will be recorded during the Screening Period. All relevant medical history, 
including currently active conditions and chronic conditions will be documented. Cancer 
history should include documentation of HPV or status of tumor for SCCHN. All 
pre-treatment AEs after signing ICF will also be documented.  
9.2.2 
Assessment of Safety Laboratory Parameters  
The central laboratory will provide the required materials for processing the samples, and will 
also provide instructions regarding centrifugation, processing, storage and shipment of 
samples (as outlined in a Laboratory Manual). The Investigator will receive a laboratory 
report for information on a per visit basis. Clinical significance including any related 
comments will be collected.  As of Amendment 3, central laboratory analysis of samples will 
no longer be required (see Section 9.5); laboratory samples should be collected and analyzed 
in accordance with site standard of care procedures for the particular type of cancer.  
Clinical laboratory parameters assessed in this study are displayed in Table 9.2.2-1. Serum 
samples will be drawn for the determination of ADA as specified in Table 10.2-1. 
Any clinically important abnormal laboratory values noted during the Screening period will 
be recorded as medical history. If any post-treatment results are judged as being clinically 
significant by the Investigator, the Investigator should consider whether the result should be 
recorded as an AE. If deemed necessary, laboratory parameters may be retested or followed 
as unscheduled tests. Unscheduled tests should be performed by the central laboratory unless 
immediate results are required for the subject’s safety. At minimum, the following laboratory 
abnormalities should be collected as an AE. 
• 
Any laboratory test result that meets the criteria for a SAE; 

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• 
Any laboratory abnormality that requires the subject to have IMP discontinued or 
interrupted; 
• 
Any laboratory abnormality that requires the subject to receive specific corrective 
therapy. 
All clinically important abnormal laboratory tests occurring during the study will be repeated 
at appropriate intervals until (1) the value returns to baseline, (2) the value is judged to be 
clinically acceptable by the Investigator and the Sponsor, or (3) a diagnosis that explains the 
abnormal laboratory value is made. When possible, the Investigator should report the clinical 
diagnosis rather than the laboratory term (e.g., anemia versus low hemoglobin). 
Clinical laboratory abnormalities that qualify as AEs and any events that lead to an 
intervention (including premature discontinuation of IMP or significant additional 
concomitant therapy), should be reported and evaluated as AEs. 
Table 9.2.2-1 
Clinical Laboratory Assessments 
Laboratory Assessment 
Test to be Performed 
Serum Chemistry 
Alanine aminotransferase
Blood urea nitrogen 
Lipase
Aspartate aminotransferase
C-reactive protein 
Sodium
Albumin 
Creatinine
Total bilirubin
Alkaline phosphatase
Glucose
Total protein
Amylase 
γ-Glutamyl transferase 
Uric Acid
Thyroid Profile 
Thyroid stimulating hormone 
Free T4 
Free T3 
Coagulation Profile 
Activated partial thromboplastin time 
 
Hematology 
Hemoglobin 
White blood cells 
Hematocrit 
Differential & absolute count 
Red blood cells 
Platelet count 
Urinalysis 
Protein 
Occult blood 
Glucose 
Urobilinogen 
Serum Pregnancy Test 
To be performed for all women of childbearing potential (minimum sensitivity 
25 IU/L or equivalent units of β-human chorionic gonadotropin) 
Urine Pregnancy Test 
To be performed for all female subjects of childbearing potential (minimum 
sensitivity 25 IU/L or equivalent units of β-human chorionic gonadotropin) 
Virus Testing 
HBs-Ag, HBs-Ab, HBc-Ab, HBV-DNA 
Hepatitis C Ab and RNA 
Human immunodeficiency virus 
Cytomegalovirus serology (immunoglobulin G and M subclasses) 
Serum Tumor 
Markers, as Applicable 
Disease-specific tumor markers 
HBs-Ag=hepatitis B surface antigen; HBs-Ab=hepatitis B surface antibody; HBc-Ab=hepatitis C surface antibody; 
HBV-DNA=hepatitis B virus deoxyribonucleic acid; RNA=ribonucleic acid. 

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9.2.3 
Vital Signs 
Blood pressure and pulse rate measurements will be performed at each visit identified in 
Table 9-1. Blood pressure and pulse rate will be performed after the subject has been resting 
for at least 5 minutes. Pulse oximetry will be performed prior to the infusion of nivolumab at 
each visit identified in Table 9-1. Any new clinically relevant findings that are identified will 
be reported as AEs. 
9.2.4 
Electrocardiograms 
The subject will be supine for at least 5 minutes before the 12-lead ECG is performed. The 
12-lead ECGs will be performed during the Screening period, on Days 1, 8, and 15 of 
Cycle, 1 and at EOT. All 12-lead ECGs recorded during the study will be obtained in 
triplicate (all three 12-lead ECGs within a 5-minute time period). All 12-lead ECGs on 
dosing days must be performed prior to infusion of first IMP and at the end of infusion 
(± 10 minutes) of mogamulizumab. In case of clinically significant 12-lead ECG 
abnormalities including a non-screening 12-lead ECG that demonstrates a QTc value 
> 500 msec or QTc interval change of > 60 msec from baseline, 2 additional 12-lead ECGs 
should be obtained over a brief period (e.g., 30 minutes) to confirm prolongation. Additional 
12-lead ECGs may also be performed as clinically indicated. The Investigator or designee has 
the responsibility to read and evaluate the 12-lead ECGs for the timely assessment of subject 
safety. 
9.2.5 
Physical Examination, Eastern Cooperative Oncology Group 
Performance Status, Height, and Body Weight 
The Investigator will perform a full physical examination during the Screening period and 
EOT visits. The complete physical examination requires assessment of the following 
categories: HEENT, heart, lungs, abdomen, skin, musculoskeletal, extremities, neurological, 
lymph nodes, and ‘other’. Brief physical examination will be performed at the other 
timepoints specified in Table 9-1. Brief physical examinations will be symptom directed. All 
significant abnormal findings during the Screening period will be recorded in the Medical 
History. New abnormal findings or worsening of baseline conditions detected at follow-up 
physical examinations will be recorded as AEs. A complete physical examination should also 
be performed when a subject discontinues the trial prematurely. Height will be documented 
during the Screening period; body weight and ECOG performance status will be measured as 
specified in Table 9-1. 

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9.2.6 
Disease-response Assessments 
High-resolution computed tomography (CT) with oral or iv contrast or contrast-enhanced 
magnetic resonance imaging (MRI) are the preferred imaging modalities for assessing 
radiographic tumor response. If a subject has a known allergy to contrast material, please use 
local prophylaxis standards to obtain the assessment with contrast if at all possible, or use the 
alternate modality. In cases where contrast is strictly contraindicated, a non-contrast scan will 
suffice. Screening assessments should be performed within 28 days of start of treatment and 
at other time points as specified in Table 9-1. In addition to chest, abdomen and pelvis, all 
known or suspected sites of disease (including CNS) should be assessed during the Screening 
period and at subsequent assessments using the same imaging method and technique. If more 
than one method is used during the Screening period, then the most accurate method 
according to RECIST v. 1.1 should be used when recording data, and should again be used 
for all subsequent assessments. Bone scan, positron emission tomography scan, or ultrasound 
are not adequate for assessment of RECIST response. In selected circumstances where such 
modalities are the sole modality used to assess certain non-target organs, those non-target 
organs may be evaluated less frequently. For example, bone scans may need to be repeated 
only when CR is identified in target disease or when progression in bone is suspected. 
Subjects with signs of symptoms suggestive of brain metastasis should have an MRI of the 
brain.  
Anti-tumor activity will be evaluated using RECIST v. 1.1 (See Appendix 1) and 
irRECIST v. 1.1. Evaluations will include serum tumor markers as applicable to the subject’s 
tumor type. Tumor lesions planned for biopsy should not be used as target lesions for 
assessment of disease unless, in the opinion of the investigator, the procedure will not 
interfere with assessment of the subject’s tumor status. New lesions should be measured and 
recorded. 
For irRECIST v. 1.1 assessments, the following modifications of RECIST v. 1.1 apply: 
• 
At each time point, the measurements of baseline-selected target lesions and new 
measurable lesions should be combined into the Total Measured Tumor Burden (TMTB), 
and one combined assessment provided.  
• 
In order to be considered a new measurable lesion, a lesion must meet the same criteria as 
target lesions: a minimum 10 mm in the longest diameter for non-nodal lesions, and a 
minimum 15 mm in short axis for lymph nodes. Smaller new lesions contribute to the 
non-target or new nonmeasurable tumor burden, but do not get measured. 
• 
Up to 5 new measurable lesions may be selected. Larger lesions must be preferred as new 
measurable lesions over smaller lesions. 

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• 
Non-Target Lesions: In alignment with RECIST v. 1.1, Baseline selected non-target 
lesions can never convert to measurable lesions, not even if they increase in size at 
subsequent time points and become measurable. Only true new lesions can be measured 
and contribute to the TMTB. 
• 
All new lesions not selected as new measurable lesions are considered new 
non-measurable lesions and are followed qualitatively. Only a massive and unequivocal 
progression of new non-measurable lesions leads to an overall assessment of 
irRECIST-defined progressive disease (irPD) for the time point.  
• 
Persisting new nonmeasurable lesions prevent irCR. 
• 
In the absence of clinical deterioration, progression should be confirmed no less than 
4 weeks after the initial irPD assessment. 
9.2.7 
Tumor Biopsies 
Tumor biopsies will be required during the Screening period, except as indicated in the 
Inclusion Criteria, (Section 7.2) and at Week 10 (unless the tumor is inaccessible for biopsy). 
Specific instructions for tumor biopsy and tumor archival sample collection, labeling, storage, 
packaging, and retention will be provided in the Laboratory Manual. 
9.2.7.1 
Microsatellite Instability Testing  
Microsatellite instability high (MSH) in tumors refers to changes in 2 or more of the 
5 National Cancer Institute-recommended panels of microsatellite markers in tumor tissue. 
The original (1997) Bethesda guidelines proposed a panel of 5 microsatellite markers for the 
uniform analysis of MSI in HNPCC. This panel, which is referred to as the Bethesda panel, 
included 2 mononucleotide (BAT-25 and BAT-26) and 3 dinucleotide (D5S346, D2S123, 
and D17S250) repeats (Rodriquez-Bigas, 1997). Individual testing sites may utilize a slightly 
different panel of markers incorporating alternative mononucleotide or dinucleotide markers. 
Regardless of the panel of markers, samples with instability in 2 or more of these markers are 
defined as MSI-High (MSI-H), whereas those with one unstable marker are designated as 
MSI-L. Samples with no detectable alterations are MSS. 
Sites should query subject’s medical history for prior MSI testing detected by an accredited 
laboratory per local regulations to select subjects with CRC for non-MSI-H tumors. 
Non-MSI-H status in potential subjects will be done prior to the Screening period as part of 
standard diagnostic testing by Investigators. A polymerase chain reaction (PCR) test will be 
utilized for repeat testing of the non-MSI-H cohort and for testing of responders in other 
cohorts. Additional tumor samples must be sent to the Sponsor for future confirmatory testing 
for confirmatory studies of the in vitro diagnostic. A lab manual separate from the protocol 
will provide detailed information regarding MSI testing and sample requirements. 

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9.2.7.2 
PD-L1 Testing 
Archival (or fresh) formalin-fixed, paraffin-embedded tumor tissue must be sent to a third 
party laboratory for determination of PD-L1 status using the analytically validated IHC assay. 
Either a tissue block or a minimum of 10 unstained tumor tissue sections are acceptable. 
Submission of fewer than 10 unstained slides may be acceptable in some circumstances 
following discussion with the Medical Monitor. 
An associated pathology report must be submitted with each tumor tissue specimen. 
PD-L1 stained tissue samples will be assessed by a pathologist at a central laboratory 
identified by the Sponsor and scored as PD-L1 expressing if membrane staining is observed 
in ≥ 1% tumor cells among a minimum of 100 evaluable tumor cells. 
PD-L1 results will be available prior to enrollment for Phase 2 subjects with non-squamous 
NSCLC. 
9.3 
End of Treatment 
End-of-Treatment (EOT) evaluations should be performed within 2 weeks after last dosing 
visit or of the decision to discontinue IMP. The EOT visit should be performed before the 
start of new anti-cancer therapy.  
9.4 
Post-treatment Follow-up Period 
The first follow-up visit will be 30 days (± 5 days) after the last dose of IMP. The second 
follow-up visit will be 100-110 days after the last dose of IMP. Adverse events and SAEs 
with onset up to 100 days after the last dose of IMP should be reported, as should any SAEs 
that occur after that time and are considered potentially related to IMPs or study procedures. 
Subjects will be contacted at least every 100 days after the last dose for survival follow up 
and recording of new anti-cancer therapies. All new treatments for cancer should be recorded, 
including nivolumab if received after discontinuation from this study. Subjects who complete 
or discontinue treatment without progression will have tumor assessments collected until a 
new anti-cancer therapy is started, unequivocal disease progression is documented, 
withdrawal of consent for follow-up contacts, or death.  
9.5 
Study Procedures for Subjects Ongoing at the Time of Data Cutoff for 
Completion of Analyses and Preparation of CSR 
For subjects who are continuing to receive study treatment at the time of data cutoff for 
completion of analyses and preparation of the CSR, the Sponsor will continue to supply study 

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drug (mogamulizumab and nivolumab) until the subject has completed the maximum 
treatment period of 96 weeks from Cycle 1 Day 1 (Section 6.3) or until the subject meets one 
of the criteria for removal from therapy as described in Section 7.5.  
Procedures to be followed for all ongoing subjects, i.e., subjects who are continuing to 
receive study treatment or who are in safety or survival follow-up, at the time of data cutoff 
are described below.  These procedures should be implemented upon notification by the 
Sponsor and approval by the appropriate IRB.  
Study Drug Administration (Subjects Actively Receiving Study Treatment) 
Study treatment should continue to be administered according to the protocol (as specified in 
Section 8.1) and the Pharmacy Manual until a maximum treatment period of 96 weeks from 
Cycle 1 Day 1 (Section 6.3) or until any of the criteria for removal of subjects from therapy 
are met (as defined in Section 7.5).   
Efficacy and Safety Assessments 
Investigators should follow study subjects in accordance with the standard of care at their 
Institution with respect to assessments of disease status and safety/tolerability, including the 
use of local clinical laboratories.  There will be no further central laboratory requirements. 
Blood samples for pharmacokinetic (PK), pharmacodynamic (PD) and anti-drug antibody 
(ADA) analyses will no longer be collected.  
Survival follow-up contacts and procedures will be discontinued for all subjects.  
Data Collection 
Data entry in the electronic data capture system, defined as the clinical database, will be 
terminated for all subjects and all data (including SAEs and treatment-related AEs), upon 
written notification by the Sponsor.  
Required data collection will be limited to SAEs and treatment-related AEs, which will be 
reported only to the KKD Drug Safety Surveillance Department using the SAE form (see 
Section 10.3.2.2.1).   

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10 
EFFICACY, PHARMACOKINETIC, SAFETY, AND OTHER 
VARIABLES 
10.1 Study Endpoints 
Primary Endpoints: 
• 
Safety and tolerability will be evaluated by assessing AEs, and changes in physical 
examination findings, vital sign measurements, 12-lead ECG readings, and clinical 
laboratory evaluations. 
Secondary Endpoints: 
• 
Best overall response (BOR) evaluated using RECIST v. 1.1. BOR is defined as the best 
response designation recorded between the date of first dose of IMP and the date of 
subsequent anti-cancer therapy (excluding on-treatment palliative radiotherapy of 
non-target bone or CNS lesions). Note: Continuation of nivolumab after discontinuing 
combination therapy does not count as start of new therapy for this definition. A BOR of 
CR or partial response (PR) requires confirmation of the assessment at least 4 weeks later. 
• 
Time to response (TTR): Days from Cycle 1 Day 1 through the first assessment date of 
confirmed CR/PR using RECIST v. 1.1; 
• 
Duration of response (DOR): Days from the first assessment date of confirmed CR/PR 
through the date of death or PD, whichever is earlier using RECIST v. 1.1; 
• 
Progression-free survival (PFS): Days from Cycle 1 Day 1 through the date of death or 
PD, whichever is earlier. For subjects whose BOR is PR or CR using RECIST v. 1.1, the 
date of first documentation of objective tumor progression or death which occurs after the 
last documentation of PR or CR will be used as the event date for PFS;  
• 
Overall survival (OS): Days from Cycle 1 Day 1 until the date of death. 
Exploratory Endpoints: 
• 
Pharmacokinetic parameters:  
– Mogamulizumab: observed minimum serum concentration at the end of a dosing 
interval (Cmin) and Cmax; and  
– Nivolumab: Cmin. 
• 
Immunogenicity: Anti-mogamulizumab antibody and anti-nivolumab antibody; 
• 
Pharmacodynamic parameters: biomarkers may include, but are not limited to, immune 
cell subsets and factors such as cytokines and chemokines in tumor and/or blood. 
• 
Immune-related overall response rate and DOR evaluated using irRECIST. 
10.2 Pharmacokinetic, Pharmacodynamic, and Immunogenicity Assessments 
Blood sample collection for serum concentrations (PK), PD markers, and ADA will occur at 
baseline and at selected times during the treatment and post-treatment periods (Table 10.2-1).  

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Immunogenicity samples will be analyzed for anti-nivolumab antibodies by a validated 
immunogenicity assay; samples may also be analyzed for neutralizing antibodies by a 
validated method. Serum samples may be analyzed by an exploratory method that measures 
anti-drug antibodies for technology exploration purposes; exploratory results will not be 
reported. 
Details of the collection, storage, and shipment of samples are described in the Laboratory 
Manual. 
As of Amendment 3, blood samples for PK, PD and ADA analyses will no longer be 
collected. 

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Table 10.2-1 
Pharmacokinetic, Pharmacodynamic, and Immunogenicity Blood 
Sampling Schedule  
Sampling Timepointg 
PK Sampling 
ADA 
Sampling 
PD 
Samplinga 
Cycle 
Day  
(Visit Window) 
Pre-doseb 
End of 
Mogamulizumab 
Infusionc 
Pre-dose 
Pre-dose  
1 
1 
X 
X 
Xd 
X 
15 (± 2) 
X 
X 
- 
X 
2 
1 
X 
X 
Xd 
X 
 
15 (± 3) 
X 
X 
- 
X 
3 
1 
X 
X 
Xf 
X 
4 
1 
X 
X 
Xd 
X 
8 
1 
X 
X 
Xd 
 
12 
1 
X 
X 
Xd 
Xe 
Sampling Timepointg 
PK Sampling 
ADA 
Sampling 
PD Sampling 
Nivolumab 
Mogamulizumab 
During an Infusion-related Reaction 
X 
X 
Xd 
Xe 
Post Last Dose of 
IMPs-Follow Up 
Day 100-110 
X 
X 
Xd 
X 
a: Sampling for immune cell subset analyses by FCM pre-dose Cycles 1 to 4 and Cycles 1 and 2, Day 15. Other exploratory 
biomarkers including PGx analysis (pre- and post-treatment) will be considered for future analysis.  
b: PK Sampling at this timepoint for both nivolumab and mogamulizumab.  
c: Within 15 minutes after EOI. Collect from the arm contralateral to where the relevant IMP was administered. 
d: ADA sampling at this timepoint for both nivolumab and mogamulizumab. 
e: Only samples for cytokine assay will be drawn at this time point. 
f: ADA sampling at this timepoint only for mogamulizumab. 
g: For subjects who are ongoing, i.e., subjects who are continuing to receive study treatment or who are in safety or survival 
follow-up, at the time of data cutoff for completion of analyses, blood samples for PK, PD and ADA analyses will no 
longer be collected (see Section 9.5). 
ADA=anti-drug antibody; EOI=end of infusion; FCM=flow cytometry; IMP=investigational medicinal product; 
PD=pharmacodynamic; PGx=pharmacogenomics; PK=pharmacokinetic. 
 
10.3 Safety Assessments  
Adverse events; clinical laboratory tests (serum chemistry, thyroid function testing, 
hematology, coagulation profile, and urinalysis); immunogenicity; vital signs; 12-lead ECGs; 
and physical examination (including body weight, etc.) will be evaluated to determine the 
safety profile in this combination regimen. 
(See Section 9.5 for reporting requirements/procedures for subjects who are ongoing in the 
study, i.e., subjects who are continuing to receive study treatment or who are in safety or 
survival follow-up, at the time of data cutoff for completion of analyses.) 

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10.3.1 
Definitions 
10.3.1.1 
Adverse Events 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product and which does not necessarily have a causal 
relationship with the treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding, for example), symptom or disease temporally 
associated with the use of an IMP (or biologic) whether or not considered related to the IMP. 
An AE includes but is not limited to:  
• 
Any clinically significant worsening of a pre-existing condition;  
• 
An AE occurring from overdose of an IMP; 
• 
An AE occurring from abuse (e.g., use for non-clinical reasons) of an investigational or 
marketed product. 
The Investigator will inquire about AEs at all subject visits by asking the subject a 
non-leading question such as:  “How have you been feeling since your last visit?” All AEs, 
whether observed by the Investigator or reported by the subject, must be collected. The 
collection of AE and SAE information commences following the subject’s written consent to 
participate in the study. If a subject experiences an AE or SAE, the subject will receive 
appropriate treatment and supportive care as necessary, and the Investigator will continue to 
follow up until there is a return to the subject’s baseline condition, or until a clinically 
satisfactory resolution is achieved. 
Clinical laboratory abnormalities that qualify as AEs (other than those meeting the definition 
for serious) and any events that lead to an intervention (including premature discontinuation 
of IMP or additional concomitant therapy), other than those reported as SAEs, will be 
reported and evaluated as AEs. Any clinically important changes noted during interim or final 
physical examinations, 12-lead ECGs, x-rays, or any other potential safety assessments, 
whether or not these procedures are required by the protocol, must also be recorded. 
For this study, disease progression should not be reported as an AE. Lymphopenia and 
leukopenia are expected pharmacologic effects of mogamulizumab and should also not be 
reported as an AE for this study. Lymphocytes and white blood cell counts will be monitored 
and evaluated with the laboratory data. 
10.3.1.2 
Serious Adverse Events 
An SAE is defined as any AE that: 
• 
Results in death; 

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• 
Is immediately life-threatening;  
– The term “life-threatening” as part of the definition of “serious” refers to an event in 
which the subject was at risk of immediate death at the time of the event; it does not 
refer to an event that hypothetically might have caused death if it were more severe; 
– If an event is Grade 4 by CTCAE v. 4.03, it does not necessarily meet the definition 
for life-threatening as is required for expedited regulatory reporting of SAEs. 
• 
Requires inpatient hospitalization or prolongation of existing hospitalization. 
– Hospitalizations for pre-planned procedures are not considered SAEs. 
• 
Results in persistent or significant disability or incapacity or substantial disruption of the 
ability to conduct normal life functions; 
• 
Is a congenital anomaly or birth defect; 
• 
Is another important medical event. Important medical events are those that may not result 
in death, be life-threatening, or require hospitalization, but may be considered an SAE 
when, based upon appropriate medical judgment, they may jeopardize the subject and 
may require medical intervention to prevent one of the outcomes listed above.  
– Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, or blood dyscrasias that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
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 headache). This is not the same as 
“serious,” which is a regulatory definition as outlined above. Seriousness (not severity) serves 
as a guide for defining regulatory reporting obligations. 
10.3.1.3 
Causality 
The causal relationship of each AE to the trial medication must be determined by a medically 
qualified individual. The causal relationship should be assessed as one of the following: 
Table 10.3.1-1 Relationship of Adverse Events 
Related: 
There is a reasonable causal relationship between the study drug administration and the AE 
Not related: 
There is not a reasonable causal relationship between study drug administration and the AE 
The term “reasonable causal relationship” means there is evidence to suggest a causal relationship 
AE=adverse event. 
 
10.3.1.4 
Severity 
The severity of AEs will be graded using CTCAE v. 4.03. If a subject is responding to an 
ongoing steroid taper and no other intervention is required, the steroid taper should not be 

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considered an intervention for the purpose of CTCAE grading of AEs that have otherwise 
resolved to ≤ Grade 1. 
10.3.2 
Adverse Event Reporting 
10.3.2.1 
Reporting Period 
The collection of AE information begins following the subject's written consent to participate 
in the study. For screen failures, SAEs should be collected and recorded only until the subject 
fails screening or withdraws consent to participate in the study, except for SAEs that occur 
outside of that window which are attributed to screening-specific procedures. All AEs with 
onset after signing of the ICF should be collected. Adverse events which occur prior to first 
administration of IMP should be identified as occurring pretreatment. No AE data should be 
entered on the electronic Case Report Form (eCRF) for screen failures. All AEs and SAEs 
with onset up to 100 days after the last dose of IMP should be reported. The Investigator 
should report any SAE that occurs after this period if the SAE is believed to be related to IMP 
or to a protocol-specific procedure. (NOTE: Upon implementation of Amendment 3, any 
treatment-related AEs and SAEs with onset after the last dose of IMP should be reported at 
the discretion of the Investigator to KKD Drug Safety Surveillance Department using the 
SAE form (Section 10.3.2.2.1). 
10.3.2.2 
Reporting Instructions 
The description of each AE will identify the subject, date of onset, the date of resolution, the 
severity of the event, the action taken regarding the IMP, the outcome of the event, and the 
relationship of the event to the IMP.  
Standard medical terminology should be used to document AEs. In the case of signs and 
symptoms, the underlying illness or diagnosis will be recorded as the event when known. For 
SAEs, a single term for the diagnosis or underlying illness should be recorded on the SAE 
Report form; in the event this is unknown, the chief sign/symptom making the event serious 
should be recorded. The terms “death” (an outcome) and “hospitalization” may be used for 
initial reports only if no further information is available in order to avoid a delay in expedited 
reporting; however, an adequate follow-up report must follow in which the term “death” or 
“hospitalization” is replaced by the cause of death or hospitalization. 
All IMP-related serious and non-serious AEs must be followed for a final outcome until 
resolution or stabilization. An outcome of “unknown” is not considered to be an acceptable 
final outcome. An outcome of not resolved is an acceptable final outcome for non-serious 
AEs at the end of a subject’s participation in a study, and for SAEs at database lock. 

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10.3.2.2.1 Serious Adverse Event Reporting Instructions 
Serious adverse events require expeditious handling to comply with regulatory requirements. 
Any SAE occurring in a clinical study subject and follow-up SAE documentation must be 
reported to the Sponsor’s Drug Safety Surveillance Department or designee within 24 hours 
of the Investigator having knowledge of the SAE. 
 
 
The Investigator or other qualified individual at the investigative site must complete the SAE 
form and fax or e-mail it to the Sponsor or designee. All telephone communication 
regarding an SAE must be followed by a written report.  
The Investigator is obligated to immediately report to the Sponsor or designee any SAE 
occurring at any time during the reporting period (Section 10.3.2.1), independent of the 
circumstances or suspected cause. In addition, the Investigator must promptly report to the 
Sponsor any SAE occurring at any other time after completion of the study if a causal 
relationship to IMP is suspected. For all SAEs, the Investigator is obligated to pursue and 
provide information as requested by the Sponsor in addition to that requested on the SAE 
form. Information must include a description of the AE in sufficient detail to allow for a 
complete medical assessment of the case and independent determination of causality. 
Supporting documentation such as hospital discharge summaries or pertinent laboratory 
reports should also be sent to the Sponsor. In the case of a subject death, a summary of 
available autopsy findings must be submitted as soon as possible to the Sponsor. The 
Investigator will ensure that information reported immediately by telephone or other means 
and information entered on the SAE form is accurate and consistent. 
10.3.2.2.2 Notification of Institutional Review Board or Ethics Committee of 
Serious Adverse Events 
The Investigator must comply with the applicable regulatory requirements related to the 
reporting of SAEs to the IRB. The IRB must be informed in a timely manner by the 
Investigator of SAEs occurring at their site during the study. Investigators must also submit 
safety information provided by the Sponsor to the IRB as per IRB standard operating 
procedures. 

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10.3.3 
Other Significant Adverse Events 
10.3.3.1 
Urgent Safety Measures 
In accordance with the principles of GCP as laid out in ICH E6, the Investigator(s) has/have 
primary responsibility for assuring subject safety throughout the performance of study 
procedures. An urgent safety measure is defined as any measure which an Investigator may 
need to implement which is a deviation from, or a change in, the protocol to eliminate an 
immediate hazard(s) to trial subjects without prior IRB approval/favorable opinion. 
The Investigator may take appropriate urgent safety measures in order to protect the subjects 
of a clinical trial against any immediate hazards to their health or safety. However, the 
Investigator must inform the Sponsor within 24 hours of having taken such measures. 
10.3.3.2 
Adverse Events That Qualify as Dose-limiting Toxicity 
Any AE(s) that qualify as DLT(s) and occur within the DLT evaluation period must be 
reported to the Sponsor’s Medical Monitor via phone contact and also to the Drug 
Safety Surveillance Department or designee using an SAE form (whether or not the 
DLT is considered an SAE) within 24 hours of the Investigator having knowledge of the 
DLT. The appropriate forms must also be completed within 24 hours. 
Refer to the Procedure Manual for reporting instructions.  
10.3.3.3 
Infusion-related Reactions 
While all infusion-related reactions should be reported as AEs, and any that 
additionally meet serious criteria should also be reported to the Sponsor's Drug Safety 
and Surveillance Department per SAE reporting guidelines, all Grade ≥ 3 
infusion-related reaction must be reported to the Sponsor’s Drug Safety Surveillance 
Department or designee within 24 hours of the Investigator having knowledge of the 
event using an SAE form (whether or not the infusion-related reaction is considered an 
SAE). 
 
 
Refer to the Procedure Manual for reporting instructions. The Investigator or designee at the 
investigative site must complete the SAE form and fax or e-mail it to the Sponsor or 
designee. 
Recommendations for the management of infusion-related reactions are provided in 
Section 8.2.2. 

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10.3.4 
Overdose 
An overdose is defined as the accidental or intentional administration of any dose of an IMP 
that is > 10% of the appropriate dose. An overdose should be reported, whether or not 
associated with an AE/SAE, using an SAE form. 
10.3.5 
Pregnancy Reporting 
Pregnancy in a female trial participant or partner of a male trial participant must be avoided. 
However, should a pregnancy occur, this process is aimed at ensuring the appropriate 
monitoring of the potential risk related to IMP exposure of pregnant women and/or fetuses as 
well as the risks associated with exposure of a father, regarding congenital abnormalities or 
birth defects in their offspring. It also ensures compliance with applicable international and 
local regulations. The requirements are applicable to all subjects following exposure to IMP. 
Female trial subjects:  The subject must be advised by the Investigator to inform him/her 
immediately if she suspects she may be pregnant. The Investigator is obligated to 
immediately report to the Sponsor or designee any pregnancy occurring at any time after the 
subject signs the ICF and within 23 weeks after the last dose of IMP. 
Male trial subjects:  The subject must be advised by the Investigator to inform him/her 
immediately if they suspect their partner became pregnant after the subject was administered 
IMP. The Investigator is obligated to immediately report to the Sponsor or designee any 
pregnancy occurring at any time after the subject signs the ICF and within 31 weeks after the 
last dose of IMP. 
When a trial subject reports a pregnancy (post-IMP administration) to the Investigator, IMP 
should be stopped immediately and a pregnancy test should be arranged for the subject (or 
their partner) by the Investigator within seven (7) days of the pregnancy being reported. 
In the case of pregnancy, The Investigator must immediately notify the Sponsor of this event 
and report the pregnancy on the Pregnancy Surveillance Form. This includes a study subject 
as well as the partner of a study subject who becomes pregnant while the subject was 
receiving IMP. Every attempt will be made to follow the pregnancy to conclusion to obtain 
information regarding the outcome. 

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11 
DATA MANAGEMENT  
11.1 Source Data 
Source documents are where data are first recorded, and from which participants’ eCRF data 
are obtained. These include, but are not limited to, hospital records (from which medical 
history and previous and concurrent medication may be summarized), clinical and office 
charts, laboratory and pharmacy records, diaries, microfiches, radiographs, and 
correspondence. 
All documents will be stored safely in confidential conditions. The participant will be 
referred to by the trial participant number/code, not by name, in all data reported to the 
Sponsor. 
11.2 Access to Data  
Direct access will be granted to authorized representatives from the Sponsor, Contract 
Research Organization, host institution and the regulatory authorities to permit trial-related 
monitoring, audits and inspections. The Investigator(s) must accept that regulatory authorities 
may conduct an inspection to verify compliance of the study with GCP. 
11.3 Electronic Case Report Forms  
Subject data will be entered into study eCRFs, in a validated Electronic Data Capture (EDC) 
system. Management of clinical data will be performed in accordance with applicable 
industry standards and data cleaning procedures to ensure the integrity of the data. It is the 
responsibility of the investigative site to prepare and maintain the adequate and accurate 
eCRFs that have been designed by the Sponsor to record all observations and other data 
pertinent to the clinical investigation. These eCRFs are organized as an ordered series of 
electronic data entry modules specific for each scheduled and unscheduled study visit. 
Only staff listed on the “Delegation of Authority” page in the study file notebook and who 
have been appropriately trained to use the EDC system will be issued user identification (ID) 
allowing them to make entries and edits to the EDC system and to respond to queries. Only 
the Investigator will be issued a user ID allowing the application of an electronic signature to 
a completed study subject record signifying the data has been reviewed and verified as 
complete and accurate. 
The Investigator agrees to treat all subject data used and disclosed in connection with this 
study in accordance with all applicable privacy laws, rules and regulations, including all 

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applicable provisions of the Health Insurance Portability and Accountability Act and its 
implementing regulations (“HIPAA”). 
The Sponsor or designee will be responsible for the processing and quality control of the 
data. Data management will be carried out by the Sponsor or designee. The handling of data, 
including data quality control, will comply with all applicable regulatory guidelines. 
Data entry in the electronic data capture system, defined as the clinical database, will be 
terminated for all subjects and all data (including SAEs and treatment-related AEs), upon 
written notification by the Sponsor (see Section 9.5).   
11.4 Record Keeping and Archiving  
Electronic CRFs, including queries and audit trails, will be retained by the Sponsor or 
designee. Study data and other essential documents should be retained for a minimum of 
2 years after the last approval of a marketing application in an ICH region and until there are 
no pending or contemplated marketing applications in an ICH region or until at least 2 years 
have elapsed since the formal discontinuation of clinical development of the investigational 
product. However, these documents should be retained for a longer period if required by the 
applicable legal requirements. Kyowa Kirin Pharmaceutical Development, Inc. or its 
designee will inform the Investigator, in writing, as to when these documents no longer need 
to be maintained.  
All study documentation at the Investigator’s site and Sponsor’s site will be archived in 
accordance with ICH E6-GCP. 
11.5 Study Monitoring  
Study monitoring will be performed in accordance with ICH E6-GCP, the protocol, and 
applicable local regulations. 
12 
STATISTICAL METHODS AND PLANNED ANALYSIS  
12.1 General Statistical Considerations 
Tabulations of summary statistics, graphical presentations, and statistical analyses will be 
performed using Statistical Analysis System® software. Descriptive statistics (mean, standard 
deviation, median, minimum, and maximum) for continuous variables and frequency 
distributions and percentages for discrete variables will be utilized. All summaries and 
analyses conducted will be by tumor type, assigned therapy, and combined total subjects. The 
specifics for these outputs will be described in detail within the Statistical Analysis Plan. The 

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last pre-administration observation will be used as the baseline value for calculating 
post-administration changes from baseline. All data entered into the database will be 
provided in separate data listings showing individual subject values. The planning and 
reporting of statistical analysis will be carried out as described in the Sponsor’s or designee’s 
Standard Operating Procedures governing clinical studies. 
12.2 Populations to be Analyzed 
The following analysis sets will be used in the study: 
• 
Safety Analysis Set: Includes all subjects who receive at least one dose of the 
investigational product (even a partial dose of either agent).  
• 
Efficacy Analysis Set: Includes all subjects who receive combination therapy in Cycle 1 
Day 1. 
• 
Pharmacokinetic Analysis Set: Includes all subjects who provide at least one post-dose 
concentration measurement.  
• 
Pharmacodynamic Analysis Set: Includes all subjects who provide at least one 
post-dose sample. 
Evaluation of the data for this study will consist primarily of data listings and summary 
displays. Demographic and other baseline characteristic information will be summarized for 
the Safety Analysis and Efficacy Analysis Sets. Adverse events will be tabulated by body 
system, severity, and relation to treatment. Similar presentations will be provided for SAEs, 
AEs leading to discontinuation of IMP, and AEs leading to death. The tabulation of 
laboratory parameters will indicate the normal range for each parameter. Each value will be 
classified as falling above, below, or within the normal range.  
12.2.1 
Subject Disposition 
The number of subjects enrolled, completed, discontinued, and replaced will be presented by 
dose cohort including the expansion cohorts. A summary of reasons for discontinuation will 
be provided. The number of subjects in the Safety Analysis and Efficacy Analysis Sets will 
be summarized as well as the number of subjects in the Safety Analysis Set that were 
excluded from the Efficacy Analysis Set. 
12.2.2 
Demographic and Baseline Disease Characteristics 
Summaries will include demographics (including age, race, ethnicity, sex, height, weight, and 
body mass index, physical examination results, ECOG PS, and baseline values for 
disease-specific measurements (i.e., sum of longest diameters for solid tumors). 

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Medical/surgical history, including prior cancer treatments, will be summarized and listed by 
subject. 
12.2.3 
Prior and Concomitant Medications 
The World Health Organization Drug Dictionary will be used to classify prior and 
concomitant medications by therapeutic class and preferred term.  
12.2.4 
Investigational Medicinal Product Exposure and Compliance 
Extent of exposure in weeks for each subject for the entire treatment period will be 
calculated. Extent of exposure, total number of cycles initiated, and total number of doses 
administered for each investigational product during the treatment period will be 
summarized.  
12.3 Efficacy Analysis 
Subjects will be evaluated for tumor response, TTR, DOR, and PFS. The ORR will be 
calculated as the proportion of subjects in the Efficacy Analysis Set who are responders, i.e., 
BOR=CR and PR; the 95% exact CI for ORR will be calculated. The ORR will be derived 
using both the RECIST v. 1.1 and the irRECIST v. 1.1, based on the efficacy evaluable 
subjects in each expansion cohort for each combination therapy.  
The DOR, OS, and PFS will be estimated using the Kaplan-Meier methodology.  
12.3.1 
Sample Size Determination 
The sample size for the dose-finding phase of the study is based on a standard 3+3 
dose-finding design and depends on observed toxicity. With 2 doses under consideration, a 
maximum of 12 subjects will be required. 
The Simon’s 2-stage optimal design will be used for the expansion cohorts. A cohort may be 
considered for termination due to lack of efficacy if the observed number of tumor responses 
(either confirmed or unconfirmed) in the first stage is too small. The characteristics of this 
design depend on 2 probabilities: the false positive rate (FPR), the probability of declaring 
the experimental treatment to be superior when in fact it is no better than the historical 
standard, and the false negative rate (FNR), the probability of concluding the experimental 
treatment to be no better than the historical standard, when it fact it is superior. The table 
below presents operating characteristics of the Simon’s 2-stage design with 15% FPR and 
10% FNR for various expansion cohorts and their historical and target objective response 

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rates. For example, an initial evaluation of efficacy may be performed after 16 treated 
subjects with squamous cell NSCLC have evaluable tumor response data. Guided by the 
Futility Boundary as shown, the decision to terminate the cohort or to allow it to continue 
will be made after taking into consideration other relevant observations such as duration and 
depth of response and risk/benefit profile. The number of subjects receiving treatment at the 
time of the Stage 1 efficacy evaluation may exceed the specified Stage 1 sample size 
depending on accrual rate, response lag, and other factors. 
Upon completion of Stage 1 enrollment for a given cohort, the SRC will review available 
efficacy and safety data and determine whether enrollment into Stage 2 may continue, even if 
not all response data are yet available to determine whether the Stage 1 criteria have been 
met. The SRC may decide that enrollment may continue if the benefit risk assessment 
is perceived to be positive. 
With FPR or one-sided alpha=15% and FNR or 1-power=10%. 
Table 12.3.1-1 Sample Size Estimation by Tumor Type 
 
Response Assumptions 
Simon 2-Stage Sample Sizesa 
 
Tumor Type 
Lower 
Bound 
Historical 
Response 
Rate (%) 
Target 
Response 
Rate (%) 
Stage 1 
(n1)/Total N 
Stage 1 Response 
Futility Boundary 
(≤): stop if this 
many responses 
or fewer 
Probability of 
Early Stopping 
due to Futility 
(%) if true 
response rate= 
Lower Bound 
NSCLC SQ 
20 
40 
16/32 
3 
60 
NSCLC NSQ PD-L1 
non-expressing 
10 
30 
10/21 
0 
35 
Ovarian 
10 
30 
10/21 
0 
35 
CRC (non-MSI high) 
5 
20 
12/29 
0 
54 
SCCHN 
25 
45 
14/36 
3 
52 
HCC 
16 
36 
12/28 
6 
41 
Pancreatic 
0 
15 
15/17 
0 
>99 
a: False positive rate (FPR) or one-sided alpha=15% and false negative rate (FNR) or 1-power=10%. 
CRC=colorectal carcinoma; n1=sample size in Stage 1; N=sample size; non-MSI high=non-microsatellite instability high; 
NSCLC=non-small-cell lung cancer; NSQ=non-squamous; PD-L1=programmed cell death-ligand 1; HCC=hepatocellular 
carcinoma; SOC=Standard of care; SCCHN=squamous cell carcinoma of the head and neck. SQ=squamous. 
 
A maximum of 188 subjects will participate in the study. 

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12.3.2 
Significance Level 
Statistical tests will use a 0.15 significance level and will be 1-sided unless otherwise noted. 
Confidence intervals will be at 95% confidence level unless stated otherwise. 
12.4 Pharmacokinetic Analyses 
The following PK parameters will be estimated using the model-independent analysis: 
• 
Mogamulizumab:  Cmax, Cmin 
• 
Nivolumab:  Cmin 
The PK parameters are defined as follows:  
• 
Cmax:  observed maximum serum concentration;  
• 
Cmin:  observed minimum serum concentration at the end of a dosing interval; 
Individual serum concentrations at each sampling time point for mogamulizumab and 
nivolumab will be presented in listings. Descriptive summary statistics of serum 
concentrations including means, geometric means, ranges, standard deviations, and 
coefficient of variation will be presented by dose cohort and tumor type.  
Dose proportionality will be assessed as appropriate. 
Population PK analysis will be explored if appropriate. Additional details of the PK and 
population PK analyses will be addressed in a separate PK/PD Analysis Plan. 
12.5 Pharmacodynamic Analyses 
Pharmacodynamic data will be summarized. Changes from baseline in PD parameters may be 
used as PD markers to explore the PK/PD, PD-efficacy, and PD-safety relationships, as 
appropriate. 
Additional details of the PK/PD analyses will be addressed in a separate PK/PD Analysis 
Plan. 
12.6 Analysis of Immunogenicity Data 
The number and percentage of subjects with a positive ADA test in the screening, 
confirmatory, or neutralizing assays, if applicable, will be presented at each visit and overall 
for subjects exposed to mogamulizumab and nivolumab. Additionally, a summary of subjects 
who experienced an infusion-related reaction and had a positive ADA test in the screening, 
confirmatory, and neutralizing assays, if applicable, will be presented. All immunogenicity 
data will be listed by subject. 

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Immunogenicity may be reported for ADA positive status (such as persistent positive, 
neutralizing positive, only last sample positive, baseline positive and other positive) and 
ADA negative status, relative to baseline. Effect of immunogenicity on safety, efficacy, 
biomarkers and PK may be explored. Additional details will be described in the Statistical 
Analysis Plan. 
12.7 Analyses of Safety Data 
The safety and tolerability of the investigational products are determined by reported AEs, 
physical examinations, ECGs, vital signs, and laboratory tests. All summaries will be 
prepared for the entire Safety Analysis Set by tumor type and overall.  
All subjects will be assessed regularly for potential occurrence of AEs from the time 
following the first dose of investigational product until 100 days after the last dose. The 
CTCAE v4.03 system will be used to grade AEs. Treatment-emergent AEs will be grouped 
and tabulated by Medical Dictionary for Regulatory Activities preferred terms and system 
organ class. AEs will be classified by body system, incidence, severity, and causality. All 
treatment-emergent AEs will be summarized showing the number and percent of subjects for 
each outcome. 
The results from physical examination will be presented in the subject data listings. Vital sign 
measurements will be summarized at each infusion. The incidence of clinically significant 
laboratory abnormalities will be presented, and laboratory data will be summarized at each 
infusion by the CTCAE v. 4.03 toxicity grade. Laboratory data will be presented for subjects 
having Grade 3 or 4 changes from baseline. 
12.8 Procedures for Missing, Unused and Spurious Data 
Missing values will not be substituted by estimated values, but treated as missing in the 
statistical evaluation. All data from all subjects dosed in the study will be included in all 
listings, plots, summary tables, and statistical analyses when appropriate. 
12.9 Rules for Excluding Subjects from Analysis 
All dosed subjects will be included in the analyses unless otherwise specified. The Sponsor 
will make any decisions regarding whether any subjects or any individual values belonging to 
a subject will be excluded from the evaluations when the protocol violation is considered to 
have a negative impact on the scientific aspects and interpretation of the study results. If the 
subject has received any investigational product, all available safety data will be used. The 
reason(s) for any exclusion will be described in the Clinical Study Report (CSR). 

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12.10 Procedures for Reporting Deviations from Original Statistical Plan 
Any deviations from the statistical analysis outlined in this protocol will be described, and 
reasons for the deviations listed, in the final CSR. 
13 
ADMINISTRATION, DOCUMENTATION, AND RECORD 
KEEPING 
13.1 Ethics Committee or Institutional Review Board  
Before starting this study, the protocol (authorized by the Sponsor) will be submitted to the 
regulatory bodies/local health authorities (in accordance with local regulations) and to the 
IRB for evaluation. The protocol will also be signed by the Principal Investigator before 
submission to the IRB. The study will not start before the IRB gives written approval or a 
favorable opinion in accordance with ICH E6-GCP and all applicable regulatory bodies/local 
health authorities give approval or a favorable opinion as required. 
No changes from the final approved (authorized) protocol will be initiated without prior 
written approval from the Sponsor and without the IRB’s favorable opinion of a written 
amendment, except when necessary to eliminate immediate hazards to the subjects or when 
the change involves only logistics or administration. The Sponsor will authorize and the 
Principal Investigator(s) will sign the protocol amendment prior to submission to the IRB. 
Protocol amendments should be submitted to the IRB without delay. Any significant 
deviation from the protocol when no approved amendment exists will be regarded as a 
protocol violation, and will be addressed as such during the reporting of the study. 
13.2 Investigator’s Responsibilities 
13.2.1 
Overall Responsibilities 
The Investigator(s) is/are responsible for conducting the study in full accordance with the 
Protocol and the 2013 revision of the Declaration of Helsinki, the GCP: Consolidated 
Guideline, approved by the ICH, and any applicable national and local laws and regulations.  
13.2.2 
Subject Informed Consent 
Written and oral information about the study in a language understandable by the subject will 
be given to all subjects. Each subject’s willingness to participate in the study will be 
documented in a signed and dated ICF before any protocol-specific procedures or 
assessments are done and after the aims, methods, anticipated benefits, potential hazards, and 

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insurance arrangements in force are explained. It will also be explained to the subjects that 
they are free to refuse entry into the study and free to withdraw from the study at any time 
without prejudice to future treatment. The informed consent process will be documented in 
the subject's medical record and the Investigator will sign, date, and time the ICF after the 
subject has signed, dated, and recorded the time of informed consent. The Investigator(s) will 
keep the original consent forms and copies will be given to the subjects. 
13.2.3 
Confidentiality Regarding Study Subjects 
The Investigator(s) must assure that the privacy of the subjects, including their personal 
identity and all other personal medical information, will be maintained at all times. In eCRFs 
and other documents or image material (including materials from all examinations, e.g., MRI, 
CT scan) submitted to the Sponsor, subjects will not be identified by their names, but by 
subject ID numbers. 
Personal medical information may be scrutinized for the purpose of verifying data recorded 
in the eCRF. This may be done by the monitor(s), properly authorized persons on behalf of 
the Sponsor and/or designee, the quality assurance unit, or regulatory authorities. Personal 
medical information will always be treated as confidential. 
13.2.4 
Record Retention 
Study data and other essential documents should be retained for a minimum of 2 years after 
the last approval of a marketing application in an ICH region and until there are no pending 
or contemplated marketing applications in an ICH region or until at least 2 years have elapsed 
since the formal discontinuation of clinical development of the IMP. However, these 
documents should be retained for a longer period if required by the applicable legal 
requirements. Kyowa Kirin Pharmaceutical Development, Inc. or its designee will inform the 
Investigator, in writing, as to when these documents no longer need to be maintained.  
13.2.5 
Investigator Information 
By signing this protocol, the Investigator recognizes that certain personal identifying 
information with respect to the Investigator, and all sub-Investigators and study site 
personnel, may be used and disclosed for study management purposes, as part of a regulatory 
submissions, and as required by law. This information may include: 
• 
Name, address, telephone number, and email address; 
• 
Hospital or clinic address and telephone number; 
• 
Curriculum vitae or other summary of qualifications and credentials; 

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• 
Other professional documentation. 
Consistent with the purposes described above, this information may be transmitted to the 
Sponsor, affiliates, and agents of the Sponsor, in your country and other countries, including 
countries that do not have laws protecting such information. Additionally, the Investigator’s 
name and business contact information may be included when reporting certain SAEs to 
regulatory agencies or to other Investigators. By signing this protocol, the Investigator 
expressly consents to these uses and disclosures. 
In order to facilitate contact among Investigators, the Sponsor may share an Investigator’s 
name and contact information with other participating Investigators upon request. 
13.2.6 
Compliance with Law, Audit, and Debarment 
By signing this protocol, the Investigator agrees to:  
1) Conduct the study in an efficient and diligent manner and in compliance with this 
protocol, GCP, and all applicable regulatory requirements. 
a) Complete, and/or update the Food and Drug Administration (FDA) Form 1572 in 
a timely manner, and conduct the study in accordance with the specifications on 
Page 2 of FDA Form 1572. 
2) Allow monitoring, audits, IRB review, and regulatory agency inspection of 
trial-related documents and procedures and provide for direct access to all 
study-related source data and documents. 
b) Promptly and fully disclose to the Sponsor, and make available at the 
Investigator’s site upon request for inspection all source documentation by 
representatives of the Sponsor, IRB, or any regulatory agencies.  
c) Promptly inform the Sponsor of any regulatory agency inspection conducted for 
this study. 
d) The Investigator agrees to promptly take any reasonable steps that are requested 
by the Sponsor as a result of an audit to cure deficiencies in the study 
documentation and worksheets/eCRFs.  
3) Provide all data, and upon completion or termination of the clinical study submit any 
other reports to the Sponsor as required by this protocol or as otherwise required 
pursuant to any agreement with the Sponsor. 
4) Immediately disclose in writing to the Sponsor if any person who is involved in 
conducting the study is debarred or if any proceeding for debarment is pending or, to 
the best of the Investigator’s knowledge, threatened. Persons debarred from 
conducting or working on clinical studies by any court or regulatory agency will not 
be allowed to conduct or work on this Sponsor’s studies. 
5) The Investigator agrees to provide to the Sponsor accurate financial information to 
allow the Sponsor to submit complete and accurate certification and disclosure 
statements as required by US FDA regulations (21 Code of Federal Regulations 

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[CFR] Part 54), and other financial regulatory agencies. The Investigator further 
agrees to provide this information on a Financial Disclosure/Certification Form that is 
provided. This requirement extends to sub-Investigators. This may involve the 
transmission of information to countries that do not have laws protecting personal 
data.   
The ICH E6-GCP guidelines recommend that the Investigator inform the subject’s primary 
physician about the subject’s participation in the trial if the subject has a primary physician 
and if the subject agrees to the primary physician being informed. 
In the event the Sponsor prematurely terminates a particular trial site, the Investigator will 
promptly notify that site’s IRB. 
13.3 Financial Disclosure 
According to 21 CFR, Part 54, the Sponsor is required to completely and accurately disclose 
or certify information concerning the financial interests of a clinical Investigator (or 
investigating institution) who is not a full-time or part-time employee of the Sponsor. 
Therefore, the Investigator(s) (or investigating institution) must provide the Sponsor with 
sufficient, accurate financial certification to ensure that any financial arrangements will not 
introduce potential bias from the Investigator into the interpretation or outcome of the study. 
13.4 Insurance 
A Certificate of Insurance and/or an information leaflet containing essential information 
about the insurance coverage can be provided upon request. 
13.5 Publication Policy 
The study is part of a multicenter study; accordingly, the Institution and Principal Investigator 
of the study agree that the first publication of the results of the study shall be made in 
conjunction with the presentation of a joint, multicenter publication of the study results with 
the Investigators and the Institutions from all appropriate sites contributing data, analyses and 
comments. However, if such a multicenter publication is not submitted within twelve (12) 
months after the database has been locked, abandonment or termination of the study at all 
sites, or after Sponsor confirms there will be no multicenter study publication, the Institution 
and/or such Principal Investigator may publish the results from the institution site 
individually in accordance with the following requirements. Prior to submission of any 
materials for publication or presentation, the Institution will provide such materials or 
manuscript to the Sponsor for review. Details of the Sponsor’s publication policy can be 
found in the Clinical Trial Agreement. 

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14 
QUALITY ASSURANCE 
The trial will be conducted in accordance with the current approved protocol, ICH GCP, 
relevant regulations and standard operating procedures. Regular monitoring will be 
performed according to ICH GCP. Data will be evaluated for compliance with the protocol 
and accuracy in relation to source documents. Following written standard operating 
procedures, the monitors will verify that the clinical trial is conducted and data are generated, 
documented and reported in compliance with the protocol, GCP and the applicable regulatory 
requirements. 

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15 
REFERENCES 
1. Dunn GP, Bruce AT, Ikeda H, et al. Cancer immunoediting: from immunosurveillance to 
tumor escape. Nat Immunol. 2002;3:991-8. 
2. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid 
tumours: Revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228-47. 
3. Greenwald RJ, Freeman GH, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 
2004;23:515-48. 
4. Habicht A, Dada S, Jurewicz M, et al. A link between PDL1 and T regulatory cells in 
fetomaternal tolerance. J Immunol. 2007;179:5211-9. 
5. Ishida T, Joh T, Uike N, et al. Defucosylated Anti-CCR4 monoclonal antibody 
(KW-0761) for relapsed adult T-cell leukemia-lymphoma:  a multicenter Phase II study. 
J Clin Oncol. 2012;30:837-42. 
6. Jemal A, Bray F, Center MM. et al. Global Cancer Statistics CA Cancer J Clin 
2011;61:69–90. 
7. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyting AD. PD-1 blockade in 
tumors with Mismatch-Repair Deficiency. N Engl J Med. 2015;372:2509-20. 
8. Opdivo® [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2015. 
9. Pardoll D. Does the immune system see tumors as foreign or self? Annu Rev Immunol. 
2003;21:807-39. 
10. Paz-Ares L, Horn L, Borghaei H, Spigel DR, Steins M, Ready N, et al. Phase III, 
randomized trial (CheckMate 057) of nivolumab (NIVO) versus docetaxel (DOC) in 
advanced non-squamous cell (nonSQ) non-small cell lung cancer (NSCLC). J Clin 
Oncol. 2015;33 (suppl; abstr LBA109). 
11. Rizvi NA, Mazières J, Planchard D, et al. Activity and safety of nivolumab, an anti-PD-1 
immune checkpoint inhibitor, for patients with advanced, refractory squamous non-
small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015; 
Published online February 20, 2015 http://dx.doi.org/10.1016/S1470-2045(15):70054-9. 
12. Rodriquez-Bigas MS, Boland CR, Hamilton DEH, Henson, DE, Jass JR, Khan PM, et al. 
Commentary: a national cancer institute workshop on hereditary nonpolyposis colorectal 
cancer syndrome: meeting highlights and Bethesda guidelines. J Nat Cancer Institute. 
1997;89(23):1758-62. 

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13. Seiwert T, Haddad R, Gupta S, Mehra R, Tahara M, Berger R, et al. Anti-tumor activity 
of the anti-PD-1 antibody pembrolizumab in biomarker-unselected patients with R/M 
head and neck cancer: preliminary results from the KEYNOTE-012 expansion cohort. 
Presented at the ASCO 2015 Annual Meeting;  
14. Sharpe AH, Wherry EJ, Ahmed R, et al. The function of programmed cell death 1 and its 
ligands in regulating autoimmunity and infection. Nature Immunol. 2007;8:237-45. 
15. Spigel DR, Reckamp KL, Rizvi NA, et al. A phase III study (CheckMate 017) of 
nivolumab (anti-programmed death-1) vs docetaxel in previously treated advanced or 
metastatic squamous (SQ) cell non-small cell lung cancer (NSCLC). J Clin Oncol. 
2015;33:5s (suppl; abstr8009). 
16. Sugiyama D, Nishikawa H, Maeda Y, et al. Anti-CCR4 mAb selectively depletes 
effector-type Foxp3+CD4+ regulatory T-cells, evoking antitumor immune responses in 
humans. PNAS. 2013;110:17945-50. 
17. Svensson H, Olofsson V, Lundin S, et al. Accumulation of CCR4+ CTLA-4hi 
Foxp3+CD25aahi regulatory T-cells in colon adenocarcinomas correlate to reduced 
activation of conventional T-cells. PLoS One. 2012;7:1-11. 
18. Tobinai K, Takahashi T, Akinaga S. Targeting chemokine receptor CCR4 in adult T-cell 
leukemia-lymphoma and other T-cell lymphomas. Curr Hematol Malig Rep. 
2012;7:235-40. 
19. Velu V, Titanji K, Zhu B, et al. Enhancing SIV-specific immunity in vivo by PD-1 
blockade. Nature. 2009;458:206-10. 
20. Wang C, Thudium KB, Han M, et al. In vitro characterization of the anit-PD-1 antibody 
nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer 
Immunol Res. 2014;2:846-56. 
21. Zitvogel L, Tesniere A, Kroemer G. Cancer despite immunosurveillance: 
immunoselection and immunosubversion. Nat Rev Immunol. 2006;6:715-27. 
22. Zou W. Immunosuppressive networks in the tumour environment and their therapeutic 
relevance. Nat Rev Cancer. 2005;5:263-74. 

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16 
APPENDICES 

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Appendix 1 Response Evaluation Criteria in Solid Tumors, Version 1.1 
(RECIST v. 1.1) 
This Appendix has been excerpted from the full RECIST v. 1.1 criteria. For information 
pertaining to RECIST v. 1.1 criteria not contained in the study protocol or in this Appendix, 
please refer to the full publication (Eisenhauer, 2009). 
1 
ASSESSMENT OF OVERALL TUMOR BURDEN AND MEASURABLE 
DISEASE 
To assess objective response or future progression, it is necessary to estimate the overall 
tumor burden at baseline and use this as a comparator for subsequent measurements. 
Measurable disease is defined by the presence of at least one measurable lesion. 
1.1 
Measurability of Tumor 
At baseline, tumor lesions/lymph nodes will be categorized measurable or non-measurable as 
follows. All baseline evaluations should be performed as close as possible to the treatment 
start and never more than 4 weeks before the beginning of the treatment. 
Measurable lesions must be accurately measured in at least one dimension (longest diameter 
in the plane of the measurement to be recorded) with a minimum size of:  
• 
10 mm by CT scan - (CT scan slice thickness no greater than 5 mm) 
• 
10 mm caliper measurement by clinical exam (lesions which cannot be accurately 
measured with calipers should be recorded as non-measurable) 
• 
20 mm by chest x-ray 
• 
Malignant lymph nodes: To be considered pathologically enlarged and measurable, a 
lymph node must be ≥ 15 mm in short axis when assessed by CT scan (CT scan slice 
thickness recommended to be no greater than 5 mm). At baseline and in follow-up, only 
the short axis will be measured and followed. 
All measurements should be recorded in metric notation, using calipers if clinically assessed. 
Special considerations regarding lesion measurability include:  
Bone Lesions: 
• 
Bone scan, positron emission tomography scan or plain films are not considered adequate 
imaging techniques to measure bone lesions. However, these techniques can be used to 
confirm the presence or disappearance of bone lesions. 
• 
Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue components, 
that can be evaluated by cross sectional imaging techniques such as CT or MRI can be 
considered as measurable lesions if the soft tissue component meets the definition of 
measurability described above. 
• 
Blastic bone lesions are non-measurable 

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Cystic Lesions: 
• 
Lesions that meet the criteria for radiographically defined simple cysts should not be 
considered as malignant lesions (neither measurable nor non-measurable) since they are, 
by definition, simple cysts. 
• 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above. However, if non-
cystic lesions are present in the same patient, these are preferred for selection as target 
lesions. 
Lesions With Prior Local Treatment: 
• 
Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
loco-regional therapy, are usually not considered measurable unless there has been 
demonstrated progression in the lesion. 
Non-measurable Lesions are all other lesions, including small lesions (longest diameter 
< 10 mm or pathological lymph nodes with ≥ 10 to < 15 mm short axis), as well as non-
measurable lesions. Lesions considered non-measurable include: leptomeningeal disease, 
ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic 
involvement of skin or lung, abdominal masses/abdominal organomegaly identified by 
physical exam that is not measurable by reproducible imaging techniques. 
1.2 
Method of Assessment 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging based evaluation 
should always be performed rather than clinical examination unless the lesion(s) being 
followed cannot be imaged but are assessable by clinical examination. 
CT, MRI: CT is the best currently available and reproducible method to measure lesions 
selected for response assessment. Measurability of lesions on CT scan is based on the 
assumption that CT slice thickness is 5 mm or less. When CT scans have slice thickness 
greater than 5 mm, the minimum size for a measurable lesion should be twice the slice 
thickness. 
Chest x-ray: Chest CT is preferred over chest x-ray, particularly when progression is an 
important endpoint, since CT is more sensitive than x-ray, particularly in identifying new 
lesions. However, lesions on chest x-ray may be considered measurable if they are clearly 
defined and surrounded by aerated lung. 
Clinical lesions: Clinical lesions will only be considered measurable when they are 
superficial and ≥ 10 mm diameter as assessed using calipers. For the case of skin lesions, 
documentation by color photography including a ruler to estimate the size of the lesion is 

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suggested. As noted above, when lesions can be evaluated by both clinical exam and 
imaging, imaging evaluation should be undertaken since it is more objective and may be 
reviewed at the end of the study. 
Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be used as a 
method of measurement. If new lesions are identified by ultrasound in the course of the 
study, confirmation by CT or MRI is advised. 
Endoscopy, laparoscopy: The utilization of these techniques for objective tumor evaluation is 
not advised. 
Tumor markers: Tumor markers alone cannot be used to assess objective tumor response. 
2 
BASELINE DOCUMENTATION OF ‘TARGET’ AND ‘NON-TARGET’ 
LESIONS 
Target lesions: When more than one measurable lesion is present at baseline all lesions up to 
a maximum of 5 lesions total (and a maximum of 2 lesions per organ) representative of all 
involved organs should be identified as target lesions and will be recorded and measured at 
baseline. 
Target lesions should be selected on the basis of their size (lesions with the longest diameter), 
be representative of all involved organs, and should lend themselves to reproducible repeated 
measurements. 
Lymph nodes merit special mention since they are normal anatomical structures which may 
be visible by imaging even if not involved by tumor. Pathological nodes which are defined as 
measurable and may be identified as target lesions must meet the criterion of a short axis of 
≥ 15 mm by CT scan. Only the short axis of these nodes will contribute to the baseline sum. 
All other pathological nodes (those with short axis ≥ 10 mm but < 15 mm) should be 
considered non-target lesions. Nodes that have a short axis < 10 mm are considered non-
pathological and should not be recorded or followed. 
A sum of the diameters (longest for non-non-nodal lesions, short axis for nodal lesions) for 
all target lesions will be calculated and reported as the baseline sum diameters. The baseline 
sum diameters will be used as reference to further characterize any objective tumor 
regression in the measurable dimension of the disease. 
Non-target Lesions: All other lesions (or sites of disease) including pathological lymph 
nodes should be identified as non-target lesions and should also be recorded at baseline. 
Measurements are not required and these lesions should be followed as ‘present’, ‘absent’, or 
‘unequivocal progression’. In addition, it is possible to record multiple non-target lesions 

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involving the same organ as a single item on the case record form (e.g., ‘multiple enlarged 
pelvic lymph nodes’ or ‘multiple liver metastases’). 
3  
TUMOR RESPONSE EVALUATION AND RESPONSE CRITERIA 
3.1  
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 diameters of target lesions, 
taking as reference the baseline sum diameters 
Progressive Disease (PD): At least a 20% increase in the sum of 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 from the baseline study to qualify for PR 
nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while 
on study. 
Special notes on the assessment of target lesions 
• 
Lymph nodes: Lymph nodes identified as target lesions should always have the actual 
short axis measurement recorded and should be measured in the same anatomical plane as 
the baseline examination, even if the nodes regress to below 10 mm on study. This means 
that when lymph nodes are included as target lesions, the ‘sum’ of lesions may not be 
zero even if complete response criteria are met, since a normal lymph node is defined as 
having a short axis of < 10 mm. 
• 
Target lesions that become ‘too small to measure’: All lesions (nodal and non-nodal) 
recorded at baseline should have their actual measurements recorded at each subsequent 
evaluation, even when very small (e.g., 2 mm). If the radiologist is able to provide an 
actual measure, that should be recorded, even if it is below 5 mm. 
However, when such a lesion becomes difficult to assign an exact measure to then: 
(i) if it is the opinion of the radiologist that the lesion has likely disappeared, the 
measurement should be recorded as 0 mm. 
(ii) if the lesion is believed to be present and is faintly seen but too small to measure, a 
default value of 5 mm should be assigned (note: in case of a lymph node believed to 
be present and faintly seen but too small to measure, a default value of 5 mm should 

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be assigned in this circumstance as well). This default value is derived from the 5 mm 
CT slice thickness (but should not be changed with varying CT slice thickness). 
Lesions That Split or Coalesce on Treatment: When non-nodal lesions ‘fragment’, the 
longest diameters of the fragmented portions should be added together to calculate the target 
lesion sum. Similarly, as lesions coalesce, a plane between them may be maintained that 
would aid in obtaining maximal diameter measurements of each individual lesion. If the 
lesions have coalesced such that they are no longer separable, the vector of the longest 
diameter in this instance should be the maximal longest diameter for the ‘coalesced lesion’. 
3.2  
Evaluation of Non-target Lesions 
While some non-target lesions may actually be measurable, they need not be measured and 
instead should be assessed only qualitatively at the time points specified in the protocol. 
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). 
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): Unequivocal progression of existing non-target lesions. (Note: the 
appearance of one or more new lesions is also considered progression). 
The concept of progression of non-target disease requires additional explanation as follows: 
• 
When the patient also has measurable disease: To achieve ‘unequivocal progression’ on 
the basis of the non-target disease, there must be an overall level of substantial worsening 
in non-target disease such that, even in presence of SD or PR in target disease, the overall 
tumor burden has increased sufficiently to merit discontinuation of therapy. A modest 
‘increase’ in the size of one or more non-target lesions is usually not sufficient to qualify 
for unequivocal progression status. 
• 
When the patient has only non-measurable disease: To achieve ‘unequivocal progression’ 
on the basis of the non-target disease, there must be an overall level of substantial 
worsening such that the overall tumor burden has increased sufficiently to merit 
discontinuation of therapy. A modest ‘increase’ in the size of one or more non-target 
lesions is usually not sufficient to qualify for unequivocal progression status. Because 
worsening in non-target disease cannot be easily quantified (by definition: if all lesions 
are non-measurable) a useful test that can be applied when assessing patients for 
unequivocal progression is to consider if the increase in overall disease burden based on 
the change in non-measurable disease is comparable in magnitude to the increase that 
would be required to declare PD for measurable disease: i.e., an increase in tumor burden 
representing an additional 73% increase in ‘volume’ (which is equivalent to a 20% 
increase diameter in a measurable lesion). Examples include an increase in a pleural 

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effusion from ‘trace’ to ‘large’, an increase in lymphangitic disease from localized to 
widespread, or may be described in protocols as ‘sufficient to require a change in 
therapy’. If ‘unequivocal progression’ is seen, the patient should be considered to have 
had overall PD at that point. 
3.3  
New Lesions 
The appearance of new malignant lesions denotes disease progression. The finding of a new 
lesion should be unequivocal: i.e., not attributable to differences in scanning technique, 
change in imaging modality or findings thought to represent something other than tumor (for 
example, some ‘new’ bone lesions may be simply healing or flare of pre-existing lesions). 
This is particularly important when the patient’s baseline lesions show partial or complete 
response. For example, necrosis of a liver lesion may be reported on a CT scan report as a 
‘new’ cystic lesion, which it is not. 
A lesion identified on a follow-up study in an anatomical location that was not scanned at 
baseline is considered a new lesion and will indicate disease progression. An example of this 
is the patient who has visceral disease at baseline and while on study has a CT or MRI brain 
ordered which reveals metastases. The patient’s brain metastases are considered to be 
constitute PD even if he/she did not have brain imaging at baseline. 
If a new lesion is equivocal, for example because of its small size, continued therapy and 
follow-up evaluation will clarify if it represents new disease. If repeat scans confirm that 
there is a new lesion, then progression should be declared using the date of the initial scan. 
3.4  
Tumor Markers 
Tumor markers alone cannot be used to assess objective tumor responses. If markers are 
initially above the upper normal limit, however, they must normalize in order for a patient to 
be considered as having attained a complete response. 
4  
EVALUATION OF BEST OVERALL RESPONSE 
4.1  
Time Point Response 
A response assessment should occur at each time point specified in the protocol. 
For patients who have measurable disease at baseline Appendix Table 1 provides a summary 
of the overall response status calculation at each time point. 

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Appendix Table 1:  Summary of the Overall Response Status Calculation (Time Point 
Response) - Patient with Target (+/-) Non-target Disease 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CR=complete response; NE=inevaluable; PD=progressive disease; PR=partial response; SD=stable disease 
 
4.2  
Missing Assessments and Inevaluable Designation 
When no imaging/measurement is done at all at a particular time point, the patient is not 
evaluable (NE) at that time point. If only a subset of lesion measurements are made at an 
assessment, usually the case is also considered NE at that time point, unless a convincing 
argument can be made that the contribution of the individual missing lesion(s) would not 
change the assigned time point response. This would be most likely to happen in the case of 
PD. 
4.3  
Best Overall Response: all Timepoints 
Best response determination in trials where confirmation of complete or partial response IS 
required: Complete or partial responses may be claimed only if the criteria for each are met at 
a subsequent time point as specified in the protocol. In this circumstance, the best overall 
response can be interpreted as in Appendix Table 2. 

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Appendix Table 2:  Best Overall Response When Confirmation of Complete Response 
and Partial Response Required 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NE 
NE 
NE 
a: If a CR is truly met at first time point, then any disease seen at a subsequent time point, even disease meeting PR criteria 
relative to baseline, makes the disease PD at that point (since disease must have reappeared after CR). Best response 
would depend on whether minimum duration for SD was met. However, sometimes ‘CR’ may be claimed when 
subsequent scans suggest small lesions were likely still present and in fact the patient had PR, not CR at the first time 
point. Under these circumstances, the original CR should be changed to PR and the best response is PR. 
CR=complete response; NE=inevaluable; PD=progressive disease; PR=partial response; SD=stable disease. 
 
4.4  
Special Notes on Response Assessment 
When nodal disease is included in the sum of target lesions and the nodes decrease to 
‘normal’ size (< 10 mm), they may still have a measurement reported on scans. This 
measurement should be recorded even though the nodes are normal in order not to overstate 
progression should it be based on increase in size of the nodes. As noted earlier, this means 
that patients with CR may not have a total sum of ‘zero’ on the case report form (CRF). 
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 objective progression 
even after discontinuation of treatment. Symptomatic deterioration is not a descriptor of an 
objective response: it is a reason for stopping study therapy. The objective response status of 
such patients is to be determined by evaluation of target and non-target disease as shown in 
Appendix Table 1 and Table 2. 
For equivocal findings of progression (e.g., very small and uncertain new lesions; cystic 
changes or necrosis in existing lesions), treatment may continue until the next scheduled 

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assessment. If at the next scheduled assessment, progression is confirmed, the date of 
progression should be the earlier date when progression was suspected. 
5 
ADDITIONAL CONSIDERATIONS 
5.1  
Duration of Response 
Duration of overall response: The duration of overall response is measured from the time 
measurement criteria are first met for CR/PR (whichever is first recorded) until the first date 
that recurrent or progressive disease is objectively documented (taking as reference for 
progressive disease the smallest measurements recorded on study). 
The duration of overall complete response is measured from the time measurement criteria 
are first met for CR until the first date that recurrent disease is objectively documented. 
Duration of stable disease: Stable disease is measured from the start of the treatment (in 
randomized trials, from date of randomization) until the criteria for progression are met, 
taking as reference the smallest sum on study (if the baseline sum is the smallest, this is the 
reference for calculation of PD). 
5.2  
Lesions That Disappear and Reappear 
If a lesion disappears and reappears at a subsequent time point it should continue to be 
measured. However, the patient’s response at the point in time when the lesion reappears will 
depend upon the status of his/her other lesions. For example, if the patient’s tumour had 
reached a CR status and the lesion reappeared, then the patient would be considered PD at the 
time of reappearance. In contrast, if the tumour status was a PR or SD and one lesion which 
had disappeared then reappears, its maximal diameter should be added to the sum of the 
remaining lesions for a calculated response: in other words, the reappearance of an apparently 
‘disappeared’ single lesion amongst many which remain is not in itself enough to qualify for 
PD: that requires the sum of all lesions to meet the PD criteria. The rationale for such a 
categorization is based upon the realization that most lesions do not actually ‘disappear’ but 
are not visualized because they are beyond the resolving power of the imaging modality 
employed. 
5.3  
Use of Fluorodeoxyglucose-Positron Emission Tomography 
While fluorodeoxyglucose-positron emission tomography (FDG-PET) response assessments 
need additional study, it is sometimes reasonable to incorporate the use of FDG-PET 
scanning to complement CT scanning in assessment of progression (particularly possible 
‘new’ disease). New lesions on the basis of FDG-PET imaging can be identified according to 
the following algorithm: 

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a) Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of 
PD based on a new lesion. Confirmatory CT is recommended. 
b) No FDG-PET at baseline and a positive FDG-PET at follow-up: 
– If the positive FDG-PET at follow-up corresponds to a new site of disease 
confirmed by CT, this is PD. 
– If the positive FDG-PET at follow-up is not confirmed as a new site of disease 
on CT, additional follow-up CT scans are needed to determine if there is 
progression occurring at that site (if so, the date of PD will be the date of the 
initial abnormal FDG-PET scan). 
If the positive FDG-PET at follow-up corresponds to a pre-existing site of disease on CT that 
is not progressing on the basis of the anatomic images, this is not PD.  
 
 
 
 

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Appendix 2 Child-Pugh Score 
 
Measure 
1 point 
2 points 
3 points