Efficacy and Safety of UV1 Vaccination in Combination With Nivolumab and Ipilimumab as First Line Treatment of Patients With Unresectable or Metastatic Melanoma (INITIUM Study)
Phase: PHASE2
Conditions: Malignant Melanoma
Sponsor: Ultimovacs ASA

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INITIUM Protocol 
A Randomized Phase II, Open-label, Active-controlled, Multicenter Study 
Investigating the Efficacy and Safety of UV1 Vaccination in Combination with 
Nivolumab and Ipilimumab as First-line Treatment of Patients with 
Unresectable or Metastatic Melanoma (UV1-202)  
 
Protocol Number, Version and Date: 
UV1-202, Version 5.0 (Final), 22 Sep 2023 
Study Phase: 
Phase II 
Sponsor Name and Legal Registered Address: 
Ultimovacs ASA 
Ullernchausséen 64, N-0379 Oslo, Norway 
 
Regulatory Agency Identifying Numbers: 
Investigational New Drug: 
17546 
EudraCT:  
 
 
2019-002026-75 
 
 
Information described herein is confidential and may be disclosed only with the express written 
permission of the Sponsor. 
 
 

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Sponsor: 
 
 
Øivind Foss, DrSc 
Head of Clinical Operations, Ultimovacs ASA 
 
Date 
 
 
Kevin J. Carroll, Dr 
Consultant Statistician, KJC Statistics 
 
Date 
 
 
Jens Bjørheim, MD, PhD 
Chief Medical Officer, Ultimovacs ASA 
 
Date 
 
 
 
 
 

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Table of Contents 
 
Table of Contents ............................................................................................................................ 3 
List of In-text Tables and Figures ................................................................................................... 7 
1 
Synopsis .................................................................................................................................... 8 
2 
Introduction............................................................................................................................. 18 
2.1 
Malignant Melanoma...........................................................................................................18 
2.2 
Checkpoint Inhibitors for Advanced Malignant Melanoma ................................................18 
2.2.1 
Checkpoint Inhibitors Monotherapy ............................................................................... 18 
2.2.2 
Combination of Nivolumab and Ipilimumab ................................................................. 19 
2.3 
The UV1 Vaccine ................................................................................................................20 
2.4 
Clinical Data on UV1 Vaccination ......................................................................................21 
2.5 
Rationale for Combination of UV1 with Checkpoint Inhibitors .........................................24 
2.6 
Rationale for Dose and Administration Regimen ................................................................25 
2.7 
Rationale for Study Design .................................................................................................27 
2.8 
Benefit/Risk Assessment .....................................................................................................28 
3 
Objectives and Endpoints ....................................................................................................... 30 
4 
Study Design ........................................................................................................................... 31 
4.1 
Overall Design .....................................................................................................................31 
4.2 
Measures to Minimize Bias: Randomization and Blinding .................................................34 
5 
Study Population ..................................................................................................................... 35 
5.1 
Inclusion Criteria .................................................................................................................35 
5.2 
Exclusion Criteria ................................................................................................................36 
6 
Treatments .............................................................................................................................. 38 
6.1 
Study Drugs .........................................................................................................................38 
6.1.1 
Sargramostim .................................................................................................................. 38 
6.1.2 
UV1 ................................................................................................................................ 39 
6.1.3 
Nivolumab ...................................................................................................................... 40 
6.1.4 
Ipilimumab ..................................................................................................................... 40 
6.1.5 
Administration of Study Drugs ...................................................................................... 40 
6.1.6 
Preparation/Handling/Storage/Accountability ............................................................... 41 
6.1.7 
Treatment of Allergic Reactions to UV1 Vaccination .................................................... 42 

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6.1.8 
Dose Modification .......................................................................................................... 42 
6.1.9 
Overdose ......................................................................................................................... 42 
6.2 
Concomitant Medication .....................................................................................................43 
6.2.1 
Prohibited Medications During Induction Period ........................................................... 43 
6.2.2 
Permitted Medications During Induction Period ............................................................ 43 
6.2.3 
New Anticancer Treatment ............................................................................................. 44 
6.3 
Treatment After Progressive Disease ..................................................................................44 
7 
Study Duration and Schedule of Activities ............................................................................. 45 
7.1 
Screening .............................................................................................................................50 
7.1.1 
Screen Failures ............................................................................................................... 50 
7.2 
Induction Period ..................................................................................................................50 
7.2.1 
Discontinuation of Induction Therapy ............................................................................ 50 
7.3 
Follow-up Period .................................................................................................................52 
7.3.1 
Safety Follow-up Visit .................................................................................................... 52 
7.3.2 
Response Follow-up Visits ............................................................................................. 52 
7.3.3 
Survival Follow-up Visits ............................................................................................... 53 
7.4 
Withdrawal of Consent ........................................................................................................54 
7.5 
Lost to Follow-up ................................................................................................................54 
7.6 
End of Study ........................................................................................................................55 
8 
Study Assessments and Procedures ........................................................................................ 56 
8.1 
Efficacy Assessments ..........................................................................................................56 
8.1.1 
Assessment of Tumor Response ..................................................................................... 56 
8.2 
Safety Plan and Assessments ...............................................................................................57 
8.2.1 
Independent Data Monitoring Committee ...................................................................... 58 
8.2.2 
Physical Examinations .................................................................................................... 59 
8.2.3 
Vital Signs ...................................................................................................................... 59 
8.2.4 
Eastern Cooperative Oncology Group ............................................................................ 59 
8.2.5 
Clinical Safety Laboratory Assessments ........................................................................ 59 
8.2.6 
Toxicity of the Study Drugs............................................................................................ 60 
8.3 
Adverse Events ....................................................................................................................60 
8.3.1 
Definitions ...................................................................................................................... 60 
8.3.2 
Classification of Adverse Events .................................................................................... 63 
8.3.3 
Adverse Event Reporting and Follow-up ....................................................................... 65 
8.3.4 
Expedited Reporting ....................................................................................................... 67 
8.3.5 
Regulatory Reporting Requirements for Investigator and Sponsor ............................... 67 

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8.3.6 
Pregnancy ....................................................................................................................... 68 
8.4 
Exploratory Assessments .....................................................................................................69 
8.4.1 
Biomarkers ..................................................................................................................... 70 
8.5 
Extended Exploratory Cohort ..............................................................................................70 
8.6 
Single Arm UV1 Cohort ......................................................................................................70 
9 
Statistical Methods.................................................................................................................. 71 
9.1 
Statistical Hypothesis ..........................................................................................................71 
9.2 
Sample Size Determination .................................................................................................71 
9.3 
Analysis Populations ...........................................................................................................72 
9.4 
Statistical Analysis...............................................................................................................72 
9.4.1 
General Considerations .................................................................................................. 72 
9.4.2 
Efficacy Analyses ........................................................................................................... 72 
9.4.3 
Safety Analyses .............................................................................................................. 74 
9.4.4 
Exploratory Analyses ...................................................................................................... 74 
9.5 
Timing of the Analyses ........................................................................................................74 
10 Regulatory, Ethical, and Study Oversight Considerations...................................................... 76 
10.1 Regulatory and Ethical Considerations ...............................................................................76 
10.2 Financial Disclosure ............................................................................................................76 
10.3 Informed Consent Process ...................................................................................................77 
10.4 Data Protection ....................................................................................................................77 
10.5 Dissemination of Clinical Study Data .................................................................................78 
10.6 Data Quality Assurance .......................................................................................................78 
10.7 Source Documents ...............................................................................................................78 
10.8 Study and Site Closure ........................................................................................................79 
10.9 Publication Policy ................................................................................................................80 
10.10 Protocol Approval and Amendment ....................................................................................80 
10.11 Liability and Insurance ........................................................................................................80 
10.12 Access to Source Data .........................................................................................................81 
Appendix 1 Clinical Laboratory Tests .......................................................................................... 82 
Appendix 2 Extended Exploratory Cohort (N= approximately 40 patients) ................................ 84 
Appendix 3 Eastern Cooperative Oncology Group Performance Status Scale ............................ 90 
Appendix 5 Abbreviations ............................................................................................................ 95 

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Appendix 7 Single Arm UV1 Cohort.......................................................................................... 101 
Appendix 8 Protocol Version Log ............................................................................................... 103 
Declaration of the National Coordinating Investigator ................................................................ 112 
Declaration of the Principal Investigator ..................................................................................... 113 

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List of In-text Tables and Figures 
TABLES 
Table 1 
Summary of Completed, Ongoing, and Planned Clinical Studies for UV1 
Vaccination ............................................................................................................ 22 
Table 2 
Study Drugs (Induction Period) ............................................................................ 38 
Table 3 
Instructions for Preparation of Sargramostim ....................................................... 39 
Table 4 
Instructions for Preparation of UV1 ..................................................................... 39 
Table 5 
Schedule of Activities – Experimental Arm.......................................................... 46 
Table 6 
Schedule of Activities – Control Arm ................................................................... 48 
Table 7 
Local Laboratory Analysis (all patients, N=154) .................................................. 82 
Table 8 
Central Laboratory Sampling for Exploratory Analyses (all patients, N=154) .... 83 
Table 9 
Extended Exploratory Cohort Assessments – Experimental Arm ........................ 86 
Table 10 
Extended Exploratory Cohort Assessments – Control Arm .................................. 86 
FIGURES 
Figure 1 
Estimated Timelines .............................................................................................. 32 
Figure 2 
Study Design ......................................................................................................... 32 
Figure 3 
McBurney’s Point ................................................................................................. 41 
Figure 4 
Time Periods for Reporting Adverse Events, Serious Adverse Events ................. 65 
 

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1 Synopsis 
INITIUM Protocol 
Protocol Title: 
A Randomized Phase II, Open-label, Active-controlled, Multicenter Study Investigating the 
Efficacy and Safety of UV1 Vaccination in Combination with Nivolumab and Ipilimumab as 
First-line Treatment of Patients with Unresectable or Metastatic Melanoma (UV1-202) 
Protocol Number, Version: 
UV1-202, Version 5.0 (Final), 22 Sep 2023 
Study Phase: 
Phase II 
Study Sites: 
The study is planned to be conducted at 40 study sites in Europe (approximately 16 sites) and the 
United States (approximately 24 sites). 
Number of Patients: 
A total of 154 patients will be randomized. It is estimated that approximately 200 patients will be 
screened to randomize 154 patients. In addition, 20 patients will be enrolled in a single arm UV1 
cohort for exploratory purposes only. The single arm UV1 cohort is planned to start after 
154 patients have been randomized in the main study.   

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Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• 
To compare progression free survival (PFS) of 
UV1 vaccination* in combination with 
nivolumab and ipilimumab to that of nivolumab 
and ipilimumab  
Primary 
• 
PFS per Response Evaluation Criteria in 
Solid Tumors (RECIST) 1.1 
Time from randomization to progressive 
disease (PD) or death from any cause  
Secondary 
• 
To compare overall survival (OS) of UV1 
vaccination in combination with nivolumab and 
ipilimumab to that of nivolumab and ipilimumab  
Secondary 
• 
OS 
Time from randomization to death from 
any cause  
• 
To compare the objective response rate (ORR) of 
UV1 vaccination in combination with nivolumab 
and ipilimumab to that of nivolumab and 
ipilimumab  
• 
ORR per RECIST 1.1  
Proportion of patients with a best response 
of complete response (CR) or partial 
response (PR)  
• 
To compare duration of response (DOR) of UV1 
vaccination in combination with nivolumab and 
ipilimumab to that of nivolumab and ipilimumab  
• 
DOR per RECIST 1.1  
Time from first CR or PR to PD or death 
from any cause  
• 
To compare the safety of UV1 vaccination in 
combination with nivolumab and ipilimumab to 
that of nivolumab and ipilimumab  
• 
Adverse events (AEs), deaths, vital signs, 
laboratory assessments, and Eastern 
Cooperative Oncology Group (ECOG) 
performance status 
Exploratory 
• 
To elucidate the immunological mechanisms 
underlying the interplay between immune 
activation provoked by UV1 vaccination and 
inhibition of tumor resistance mechanisms and 
peripheral immune tolerance induced by 
checkpoint blockade, and how biological factors 
affect the efficacy of the combination therapy 
Exploratory 
• 
Change in immune- and tumor-related 
gene, cell, and protein profiles in blood 
over time in both treatment arms (analysis 
of plasma proteins, cell-free plasma DNA, 
and cellular genomic DNA) 
• 
Other endpoints related to analysis 
conducted on biological material collected 
from the Extended Exploratory Cohort 
* UV1 vaccination includes sargramostim, used as a vaccine adjuvant, and UV1 
 

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Study Design and Methodology 
This is a randomized, open-label, active-controlled, multicenter study to investigate efficacy and 
safety of UV1 vaccination in combination with nivolumab and ipilimumab as first-line treatment 
of adult patients (≥18 years) with histologically confirmed unresectable metastatic melanoma.  
This study will consist of 3 phases: Screening, Induction period, and a Follow-up period. The 
Follow-up period includes safety, response, and survival follow-up visits. 
After a Screening period of up to 28 days, eligible patients will be randomized in a 1:1 ratio to 
receive induction therapy: UV1 vaccination in combination with nivolumab and ipilimumab in 
an experimental arm, and nivolumab and ipilimumab in a control arm. Randomization can occur 
after all Screening procedures have been completed (up to 3 days [from Day -3 until Day 1] prior 
to first dosing on Day 1) and eligibility has been confirmed. 
Patients in the experimental arm will receive 8 UV1 vaccinations over 4 cycles of nivolumab and 
ipilimumab. The UV1 vaccination will be administered alone on Days 1, 3 to 7 (2 UV1 
vaccinations within Day 3 to Day 7; consecutive dosing days not allowed), and 26, and in 
combination with nivolumab and ipilimumab on Days 10, 31, 52, and 73. 
Patients in the control arm will receive 4 cycles of nivolumab and ipilimumab on Days 1, 22, 43, 
and 64. 
Patients in both arms will start maintenance therapy 6 weeks after last dose of induction therapy. 
The maintenance therapy is nivolumab at a dose of 480 mg every 4 weeks (Q4W) according to 
the label. It is not allowed to use any other dose of maintenance therapy (eg, 240 mg every 
2 weeks). 
The study is event driven. The primary and secondary endpoints will be analyzed at the earliest 
of either (hereinafter referred to as “PFS cut-off date”) 70 PFS events reached across both 
treatment arms or 18 months post last patient randomized, at which time sponsor will notify the 
sites. From the PFS cut-off date, patients will be followed for a further 24 months for additional 
survival data; further analyses of OS data will be performed until defined end of study to provide 
evidence supportive of PFS. 
All patients will be followed up until death or until the end of study (EOS), whichever comes 
first. Estimated timelines at start of the study are outlined below. 
 
First Patient In 
 
Last Patient In 
70 PFS events reached 
 
End of Study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 months 
 
15 months 
27 months 
 
51 months 
The estimated inclusion period is 15 months; the estimated time from last randomization to 70 
PFS events reached is 12 months; the estimated time from 70 PFS events to EOS is 24 months 
and the total study duration is estimated to be 51 months from first patient in. 

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The study design and treatment are outlined below. 
 
 
 
 
 
 
 
 
 
 
The UV1 vaccination includes sargramostim, used as a vaccine adjuvant, at a dose of 75 µg and 
UV1 at a dose of 300 µg. Sargramostim is a granulocyte-macrophage-colony-stimulating factor. 
Nivolumab and ipilimumab are dosed according to label in both treatment arms: induction 
therapy of nivolumab (1 mg/kg every 3 weeks [Q3W]) and ipilimumab (3 mg/kg every 3 weeks 
[Q3W]), and maintenance therapy of nivolumab (480 mg every 4 weeks [Q4W]). 
Sargramostim and UV1 should be administered intradermally and injected at the same 
injection site (McBurney’s point) each time, located 1/3 of the distance from the anterior 
superior iliac spine to the umbilicus on the right side of the abdomen (or corresponding spot on 
the left side in case of appendectomy scar). Sargramostim is administered 10 to 15 minutes prior 
to each UV1 treatment. Nivolumab and ipilimumab are administered intravenously, starting at 
least 1 hour after the administration of UV1. 
Following the last dose of induction therapy, the patient will then enter the Follow-up period and 
perform a safety follow-up visit 30 days post last dose of induction therapy. 
Tumor assessment will be done locally at the study site using RECIST 1.1 and immune Response 
Evaluation Criteria in Solid Tumors (iRECIST) criteria. Tumor imaging will be performed 
within 14 days prior to randomization and then on Week 12 and Week 19 post randomization. 
Subsequent response follow-up imaging will be performed every 8 weeks for 32 weeks and then 
every 12 weeks. 
Patients with PD per RECIST 1.1 will have a new scan 4 to 8 weeks later to confirm PD per 
iRECIST. Patients with immune unconfirmed PD per iRECIST (iUPD), will continue at the 
Screening period  
 
 
    Induction period  
 
 
          Follow-up period  
 (Days -28 to -1) 
 
 
 
    (Days 1 to 73 / Days 1 to 64)  
                          (4 - 5 years) 
 
 
 
 
 
       
 
 
First-line 
unresectable IIIB-D 
or unresectable IV 
metastatic melanoma 
Experimental arm 
 
UV1 vaccination:  
Administered on Days 1, 3-7 (2 UV1 
vaccinations), 10, 26, 31, 52, and 73 
 
Nivolumab and ipilimumab:  
Administered on Days 10, 31, 52, and 
73 
All patients 
Safety follow-up 
Response follow-up 
Survival follow-up 
 
At the earliest of either 70 PFS 
events reached or 18 months 
post last patient randomized, 
all patients will be followed-
up for 2 years 
 
Nivolumab maintenance 
therapy (480 mg Q4W) 
according to label 
Rand 
1:1  
N = 154 
Control arm 
 
Nivolumab and ipilimumab:  
Administered on Days 1, 22, 43 and 64 

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Investigator’s discretion, with tumor imaging and treatment per protocol until immune confirmed 
PD per iRECIST (iCPD), until 70 PFS events are reached or until 18 months post last patient 
randomized (whatever comes first). Patients with iCPD per iRECIST will be discontinued from 
treatment and will proceed into the survival follow-up phase and be contacted per phone (or, at 
the investigator’s discretion visit the hospital) every 12 weeks until the earliest of either 70 PFS 
events reached or 18 months post last patient randomized. From the PFS cut-off date, the 
survival follow-up will continue in all patients every 6 months for 2 years.  
To reduce bias in evaluation of the efficacy endpoints, tumor evaluation for the statistical 
analysis of the efficacy endpoints will be done by Blinded Independent Central Review (BICR) 
according to the RECIST 1.1 criteria. All images must be submitted to the central imaging 
vendor, but the results from the BICR will not be provided to the study site. Two independent 
radiologists will perform the central imaging review without knowledge of treatment 
assignments. If there are discrepancies between the 2 readers, a standardized procedure involving 
a third reviewer for adjudication will take place. 
From signing of the Informed Consent Form (ICF) until the first dose of induction therapy, only 
AEs/serious AEs (SAEs) caused by study-specific procedures should be reported. Non-serious 
AEs should be reported from the first dose of induction therapy until 30 days after the last dose 
of induction therapy, or until new anticancer treatment is initiated (whichever comes first). All 
SAEs should be reported from the first dose of induction therapy until 70 PFS events are 
reached, until 18 months post last patient randomized or until new anticancer treatment is 
initiated (whichever comes first). Adverse events and SAEs that are ongoing beyond the required 
reporting timelines shall be followed up locally per institutional practice until resolution or 
stabilization or the patient is lost to follow up.  
During the study, an Independent Data Monitoring Committee will monitor safety information to 
ensure patient safety. 
Patients at selected sites will have the option to be Included in the Extended Exploratory Cohort 
of the study. This cohort of approximately 40 patients, randomized in a 1:1 ratio to either of the 
2 treatment arms, will have additional sampling of blood, tissue, and feces for exploratory 
purposes. A biobank will be established for current and future analysis of the samples collected. 
To support the Extended Exploratory Cohort of the study, an additional 20 patients will be 
enrolled in a single arm UV1 cohort for collection of additional biological material (Appendix 7 
Single Arm UV1 Cohort). These patients will receive the same study treatment as patients in the 
experimental arm. 
Study Population 
Inclusion Criteria 
Patients are eligible for randomization if all of the following criteria are met: 
1. Male or female patients at least 18 years of age at the time of signing the ICF. 

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2. Histologically confirmed diagnosis of unresectable stage IIIB-D, or unresectable stage IV 
malignant melanoma. Patient must have at least 1 measurable lesion at Screening 
according to the RECIST 1.1 criteria. 
Note that lesions not measurable on computed tomography or magnetic resonance 
imaging (MRI) will be considered as non-measurable lesions. 
3. Eligible for combination treatment with nivolumab and ipilimumab. 
4. An ECOG performance status of 0 or 1. 
5. Adequate organ function as indicated by the following laboratory values: 
Hematological 
a. Absolute neutrophil count ≥1,500/µL 
b. Platelet count ≥100 x 103/µL 
c. Hemoglobin ≥9 g/dL or ≥5.6 mmol/L 
Renal 
d. Creatinine ≤1.5 x upper limit of normal (ULN) 
Hepatic 
e. Total bilirubin ≤1.5 x ULN or  
direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 ULN 
f. Aspartate aminotransferase/glutamic-oxaloacetic transaminase and alanine 
aminotransferase/glutamic-pyruvic transaminase ≤2.5 x ULN for patients without 
liver metastasis or ≤5 x ULN for patients with liver metastasis. 
6. Male patients who are sexually active with a female of childbearing potential must agree 
to use an adequate method of contraception prior to the first dose through 5 months after 
the last dose of UV1 vaccination, nivolumab, or ipilimumab, whichever is administered 
last. The recommended method is using a male condom. 
7. Women of childbearing potential (WOCBP) must have a negative urine or serum/plasma 
pregnancy test. If the urine test is positive or cannot be confirmed as negative, a 
serum/plasma pregnancy test will be performed. The serum/plasma pregnancy test must 
be negative for the patient to be eligible. 
8. WOCBP must use adequate contraception. Adequate contraception must be maintained 
throughout the study, starting with the first dose through 5 months after the last dose of 
UV1 vaccination, nivolumab, or ipilimumab, whichever is administered last. The 
acceptable contraceptive methods for WOCBP included in the study are: 
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal 
contraception associated with inhibition of ovulation (oral, injectable, or implantable), 
Intrauterine device (IUD), Intrauterine hormone-releasing system (IUS), bilateral tubal 
occlusion, vasectomized partner (provided that the partner is the sole sexual partner of the 
WOCBP trial participant and that the vasectomized partner has received medical 

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assessment of the surgical success), or sexual abstinence (if this is the preferred and usual 
lifestyle of the subject)  
9. Written informed consent prior to any study-specific procedures. 
Exclusion Criteria 
Patients are not eligible for randomization if any of the following criteria are met: 
1. Previous non-melanoma malignancies unless curatively-treated and complete remission 
was achieved at least 2 years prior to randomization. Patients with prior curatively-treated 
basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or 
carcinoma in situ of the breast, or other in situ cancers are allowed irrespective of time 
passed since curative treatment. Patients with prior completely resected malignant 
melanoma are also allowed. 
2. Known brain metastases or leptomeningeal metastases. If a patient experiences 
neurological symptoms indicative of brain metastases, a brain MRI should be performed. 
3. Diagnosis of uveal or ocular melanoma. 
4. Known history or any evidence of active, non-infectious pneumonitis. 
5. History of New York Heart Association class 3-4 congestive heart failure or history of 
myocardial infarction within 6 months of starting induction therapy. 
6. Active infection requiring systemic treatment. 
7. Diagnosis of immunodeficiency. 
8. Known history of severe hypersensitivity reactions to nivolumab, ipilimumab, 
sargramostim, or their excipients. 
9. Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). No HIV 
testing is required unless mandated by local health authority. 
10. History of or active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C 
(hepatitis C virus antibody). Testing must be performed to determine eligibility. 
11. Women who are breastfeeding. 
12. Prior systemic treatment for unresectable stage IIIB-D or unresectable stage IV malignant 
melanoma. Prior systemic BRAF/MEK inhibitors or immunotherapy as neoadjuvant or 
adjuvant or other setting treatment of stage I-IIIA, resectable IIIB-D, or resectable IV if 
patient progressed earlier than 6 months after last dose of such treatment. 
13. Systemic corticosteroid treatment (doses exceeding 10 mg daily of prednisone or 
equivalent) or any other form of immunosuppressive treatment within 7 days prior to the 
first dose of induction therapy. Topical, ocular, intra-articular, intranasal, and inhalational 
corticosteroids (with minimal systemic absorption) are allowed. Physiologic replacement 
doses of systemic corticosteroids, a brief course of corticosteroids for prophylaxis 
(eg, contrast dye allergy) or for treatment of non-autoimmune conditions is permitted even 
with >10 mg/day prednisone equivalents. 

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14. Receipt of a live vaccine within 30 days prior to start of induction therapy. 
15. Receipt of any other investigational treatment within 4 weeks of the first dose of induction 
therapy. 
16. Any medical, psychological, or social condition that would make it difficult for the patient 
to participate in the study and comply with the study procedures, restrictions, and 
requirements. 
Statistical Methods 
Statistical Hypothesis 
The primary endpoint is PFS. Under the null hypothesis, the PFS hazard ratio (HR) for UV1 
vaccination in combination with nivolumab and ipilimumab versus nivolumab and ipilimumab is 
assumed to be unity. Under the alternative hypothesis, the PFS HR is assumed to be 0.60 or 
better, representing a beneficial effect on PFS for UV1 vaccination in combination with 
nivolumab and ipilimumab compared to nivolumab and ipilimumab. 
Sample Size Determination 
To test the PFS null hypothesis with 80% power and a 1-sided alpha level of 0.10, a total of 
70 PFS events are required. To generate the required 70 PFS events, 154 patients will be 
randomized over a 15-month period and followed thereafter for a minimum of 12 months. This 
will give a mean follow-up of PFS events of approximately 20 months. 
As of 19 September 2023, blinded event accrual stood at 63 PFS events. A blinded examination 
of the overall PFS Kaplan Meier curve made as of 23 July 2023, and then repeated as of 19 
September 2023, showed strong evidence for a plateau at 54 to 55% of subjects alive and without 
progression. Such a PFS curve plateau is not uncommon for IO therapies. In CheckMate 67, 
nivolumab plus ipilimumab, nivolumab alone and ipilimumab alone were evaluated in advanced 
melanoma (Hodi 2018). This study formed the basis of the sample size calculations for the 
current study and showed a prolonged PFS tail for nivolumab plus ipilimumab plateauing at 
approximately 40% subjects alive and without progression. However, the blinded data realized 
thus far, has shown a higher plateau at 54 to 55% subjects alive and without progression. 
Specifically, there seems to be very little contribution to PFS events after 18 months in the study, 
with the PFS curve nearing asymptote. The plateau in the current study commences at 
approximately 21 months post first subject randomized with an estimated 56.02% of subjects 
alive and without progression and persists thereafter for 15 months, out to 36 months at which 
time 54.32% subjects are alive and without progression, i.e. an increase in the progression rate of 
only 1.7% over 15 months. Based on the projected PFS curve, 70 PFS events are not expected to 
be reached until late 2028 at which time 69.3 events, 90% CI of (69.2, 72.3), are expected.  
Given the observed plateau in the accrual of PFS events, it has been decided to execute the 
primary analysis of PFS at the earliest of either 70 PFS events reached across both treatment 
arms or 18 months post last patient randomized.   

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Timing of Analyses 
It should be noted that this study is event driven so that the timing of the primary endpoint 
analysis is dependent upon the attainment of 70 PFS events and is not calendar based. Based on 
the assumptions supporting the sample size calculation (Hodi, 2018), it is expected that 70 PFS 
events will have accrued at around 27 months after the first patient is randomized. 
However, as of 19 September 2023, blinded event accrual stood at 63 PFS events. A blinded 
examination of the overall PFS Kaplan Meier curve made as of 23 July 2023, and then repeated 
as of 19 September 2023, showed strong evidence for a plateau at 55% of subjects alive and 
without progression. Given the observed plateau in the accrual of PFS events, it has been decided 
to execute the primary analysis of PFS at the earliest of either 70 PFS events reached across both 
treatment arms or 18 months post last patient randomized.     
The secondary endpoints will also be analyzed at the earliest of either 70 PFS events reached 
across both treatment arms or 18 months post last patient randomized. Follow-up for survival 
will continue for an additional 24 months after the PFS cut-off date at which time 60 deaths are 
expected to have accrued. 
Primary Efficacy Analyses 
A Cox proportional hazards regression model will be used to analyze PFS. The HR will be 
estimated from the model along with the associated 2-sided confidence interval (CI) and 2-sided 
p-value. The data will also be displayed using Kaplan-Meier curves and median PFS times will 
be estimated. The PFS at 12 months will be estimated from the Kaplan-Meier curves along with 
the associated 80% and 95% CIs. 
Note, patients who withdraw consent to follow-up may have missing PFS data. The impact of 
such patients on the analysis will be explored via imputation and possibly tipping point analyses. 
Full details will be provided in the Statistical Analysis Plan (SAP). 
Secondary Efficacy Analyses 
Overall Survival will be analyzed in a fashion similar to that described for PFS at the time of the 
PFS analysis. Patients who withdraw consent to follow-up may have missing OS data. The 
impact of such patients on the analysis will be explored via imputation and possibly tipping point 
analyses. Full details will be provided in the SAP. Additionally, follow-up for survival will 
continue for a further 24 months after the PFS analysis at which time 60 deaths are expected to 
have accrued. 
Objective Response Rate will be analyzed by exact logistic regression. Patients who have 
missing tumor assessment data leading to missing objective response data will be included in the 
analysis as non-responders.  
Duration of Response will be analyzed via Cox regression modelling.  
 

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Safety Analyses 
Adverse events will be summarized descriptively by treatment group, in terms of body system 
and Medical Dictionary for Regulatory Activities preferred term. Adverse events will be 
summarized in terms of the number of patients and percentage of patients experiencing related 
AEs, SAEs, AEs leading to dose interruption, AEs leading to withdrawal from randomized 
treatment, and AEs leading to death. 
Laboratory values, ECOG performance status, and vital signs will be summarized. 
Planned Timelines 
First patient in: 
 
 
 
 
 
Q2 2020 
Last patient in:  
 
 
 
 
 
H1 2022 
Primary endpoint read out: 
 
 
 
 
H1 2024 
End of study:   
 
 
 
 
 
H1 2026 
The First Patient In is defined as the timepoint when the first patient is randomized.  
 

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2 Introduction 
2.1 Malignant Melanoma 
Worldwide over 280,000 new cases of malignant melanoma were diagnosed in 2018, and it is 
estimated that more than 60,000 persons died from the disease.1  
There are 4 main subtypes of cutaneous melanomas: superficial spreading melanoma, nodular 
melanoma, lentigo malignant melanoma, and acral lentiginous melanoma. These can be 
clinically and histologically defined based on overall appearance, location, and histologic 
features of the melanocytes. The most common risk factors are of phenotypic (fair skin), genetic 
(inheriting melanocortin-1 receptor variant; presence of high numbers of common naevi, large 
congenital naevi, multiple, and/or dysplastic naevi), and external (exposure to ultraviolet 
irradiation) types. 
Melanoma is categorized into 5 stages: Stage 0 is in situ (intraepithelial) melanoma, Stages I and 
II are localized invasive cutaneous disease, Stage III is regional spread disease, and Stage IV is 
disease with distant metastasis. Over 90% of new cases are diagnosed as primary tumors without 
any evidence of metastasis and surgical excision can be curative. 
The preferred treatment options for later stages of malignant melanoma include targeted therapy 
and immunotherapy. Targeted therapy is approved for patients with gene encoding B-Raf protein 
(BRAF) mutations and includes BRAF/mitogen-activated protein kinase (MEK) inhibitor 
combinations. Approved immune therapies include the anti-cytotoxic T-lymphocyte-associated 
protein-4 antibody ipilimumab and anti-programmed cell death 1 (PD-1) antibodies 
pembrolizumab and nivolumab. 
In September 2015, the Food and Drug Administration (FDA) granted accelerated approval of 
nivolumab in combination with ipilimumab in patients with BRAF V600 wild-type, unresectable, 
or metastatic melanoma. Positive opinion from the Committee for Medicinal Products for 
Human Use for the combination recommending a change to the terms of the marketing 
authorization for nivolumab was received in April 2016. 
Many patients with unresectable or metastatic melanoma benefit from monotherapy or 
combination therapy with immune checkpoint inhibitors, but still many patients do not respond 
or become long-time survivors. Further therapeutic advances exploring additional 
immunotherapy combinations are therefore warranted. 
2.2 Checkpoint Inhibitors for Advanced Malignant Melanoma   
2.2.1 
Checkpoint Inhibitors Monotherapy 
Ipilimumab monotherapy for advanced malignant melanoma gives a median progression free 
survival (PFS) of 3 to 4 months and a median overall survival (OS) of 6 to 20 months. 
2,3,4,5,6,7,8,9,10  

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In the CheckMate-066 study, nivolumab monotherapy showed a median PFS of 5.1 months and a 
1-year OS rate of 72.9%. The median OS was not reached; however, the study demonstrated a 
statistically significant improvement in OS for the nivolumab arm compared with the 
dacarbazine arm in an interim analysis based on 47% of the total planned events for OS (hazard 
ratio [HR] for death, 0.42; 99.79% confidence interval [CI], 0.25 to 0.73; p<0.001).11 
Pembrolizumab demonstrated a median PFS of 3 to 6 months, median OS of 13 to 15 months, 
and a 2-year survival of 36% to 55%.11,12  
2.2.2 
Combination of Nivolumab and Ipilimumab 
The combination of nivolumab and ipilimumab was approved based on study CheckMate-067 
(NCT01844505), a multicenter, double-blind study in which 945 patients with previously 
untreated, unresectable, or metastatic melanoma were randomized 1:1:1 into one of the following 
arms: nivolumab and ipilimumab, nivolumab, or ipilimumab. Patients received either nivolumab 
1 mg/kg with ipilimumab 3 mg/kg intravenously every 3 weeks (Q3W) for 4 doses, followed by 
nivolumab as a single agent at a dose of 3 mg/kg by intravenous infusion every 2 weeks (Q2W) 
(nivolumab plus ipilimumab arm); nivolumab 3 mg/kg by intravenous infusion Q2W (nivolumab 
arm); or ipilimumab 3 mg/kg intravenously Q3W for 4 doses, followed by placebo Q2W 
(ipilimumab arm). Randomization was stratified by PD-L1 expression (≥5% versus <5% tumor 
cell membrane expression) as determined by a clinical study assay, BRAF V600 mutation status, 
and M stage per the American Joint Committee on Cancer staging system, 8th edition (M0, M1a, 
M1b versus M1c). Tumor assessments were conducted 12 weeks after randomization then every 
6 weeks for the first year, and every 12 weeks thereafter. The major efficacy outcome measures 
were Investigator assessed PFS per Response Evaluation Criteria in Solid Tumors (RECIST) 
v1.1 and OS. Additional efficacy outcome measures were confirmed objective response rate 
(ORR) and duration of response (DOR). 
The median PFS was 11.5 months (95% CI, 8.9 to 16.7) in the nivolumab plus ipilimumab 
group, 6.9 months (95% CI, 4.3 to 9.5) in the nivolumab group, and 2.9 months (95% CI, 2.8 to 
3.4) in the ipilimumab group. A significant improvement in PFS was observed in the nivolumab 
plus ipilimumab group as compared with the ipilimumab group (HR, 0.42; 95% CI, 0.31 to 0.57; 
p<0.0001). A significant improvement in PFS was also observed in the nivolumab group as 
compared with the ipilimumab group (HR, 0.57; 95% CI, 0.43 to 0.76; p<0.0001). The HR for 
the comparison between nivolumab plus ipilimumab and nivolumab groups was 0.74 (95% CI, 
0.60 to 0.92).6 
The analysis results at 4 years of follow-up confirmed the improvement in PFS from the 
combination treatment over ipilimumab alone and showed a survival benefit of nivolumab plus 
ipilimumab or nivolumab alone over ipilimumab. At a minimum follow-up of 48 months from 
the date that the final patient was enrolled and randomized, median OS was not reached (95% CI, 
38.2 to not reached) in the nivolumab plus ipilimumab group, 36.9 months (28.3 to not reached) 
in the nivolumab group, and 19.9 months (16.9 to 24.6) in the ipilimumab group. The HR for 
death for the combination versus ipilimumab was 0.54 (95% CI, 0.44 to 0.67; p<0.0001) and for 
nivolumab versus ipilimumab was 0.65 (0.53 to 0.79; p<0.0001). Median PFS was 11.5 months 
(95% CI, 8.7 to 19.3) in the nivolumab plus ipilimumab group, 6.9 months (5.1 to 10.2) in the 
nivolumab group, and 2.9 months (2.8 to 3.2) in the ipilimumab group. The HR for PFS for the 
combination versus ipilimumab was 0.42 (95% CI, 0.35 to 0.51; p<0.0001) and for nivolumab 

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versus ipilimumab was 0.53 (0.44 to 0.64; p<0.0001).6 At 5 years, the OS was 52% in the 
nivolumab plus ipilimumab group and 44% in the nivolumab group, as compared with 26% in 
the ipilimumab group.13,14,15 Five-year PFS was 36%, 29%, and 8% in the nivolumab plus 
ipilimumab, nivolumab, and ipilimumab groups, respectively. Among patients with tumors with 
BRAF mutations and those with tumors without BRAF mutations, OS at 5 years was 60% and 
48%, respectively, in the nivolumab plus ipilimumab group, 46% and 43% in the nivolumab 
group, and 30% and 25% in the ipilimumab group.  
Despite advances in the development of new treatment options, advanced malignant melanoma 
remains a condition with a large unmet medical need. 
2.3 The UV1 Vaccine 
UV1 is a therapeutic cancer vaccine consisting of 3 synthetically-produced peptides covering an 
epitope rich sequence within the active site of the human telomerase reverse transcriptase 
(hTERT).  
Role of Telomerase in Cancer Cell Pathogenesis 
Human telomerase reverse transcriptase is one of 2 major components of the enzyme telomerase 
which catalyses the synthesis and extension of telomeric deoxyribonucleic acid (DNA) in order 
to maintain telomere length.16  
Telomerase activity is associated with stem cell proliferation, and telomerase is highly active in 
embryonal cells and less active in stem cells and germinal cells. During embryonic development, 
telomerase activity decreases as cells differentiate17 and telomerase activity and hTERT 
messenger ribonucleic acid (RNA) are not detectable in the majority of normal adult tissues, 
including cardiac/skeletal muscle, liver, prostate, breast, pancreas, brain, lung, and kidney.18  
Telomerase activation is the major mechanism implicated in human cell immortalization and 
cancer cell pathogenesis.16 In the absence of functional telomeres, chromosomes become highly 
unstable, and this can ultimately be lethal to the cell. Tumor cells avoid this situation by turning 
on the expression of telomerase activity. Thus, immortalization involves the arrest of the process 
of telomere shortening, and telomerase is the key enzyme in this process. Telomerase activity is 
present in approximately 100% of immortal cell lines and in >85% of human tumors of various 
histological types.17,18,19 Telomerase is expressed in cancer cells at every stage of tumor 
evolution, from the cancer stem cell to circulating tumor cells. Due to its essential role for the 
immortality of tumor cells and its universal expression by most human tumors, telomerase 
represents a unique cancer antigen as a basis for immunotherapy.20 Telomerase activity is 
reflected in the up-regulated expression of hTERT.21 
The UV1 Peptides 
The hTERT peptides composing the UV1 vaccine have been selected based on analyses of 
clinical and immunological response data from long-term cancer survivors responding 
immunologically to an unrelated first-generation hTERT vaccine. It was shown that epitope 

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spreading within hTERT and T-helper type 1 (Th1) reactivity (ie, secretion of interferon gamma, 
tumor necrosis factor alpha, and interleukin-2) were associated with prolonged survival. Based 
on these analyses, 3 long novel hTERT peptides associated with clinical benefit, shown to elicit 
strong CD4 T cell responses in blood from patients across several cancer types and predicted to 
contain multiple human leukocyte antigen epitopes, were selected for the next-generation hTERT 
vaccine UV1.22,23  
The UV1 Vaccine 
The mode of action of UV1 is to activate the immune system to induce T cells that recognize 
hTERT. The efficacy of the vaccine is thought to be mediated through these T cells.  
Expression of telomerase is essential for unlimited growth and immortality of cancer cells (ie, 
the antigen is present throughout the tumorigenesis and the tumor cannot escape from 
dependence on telomerase). 21 Due to the temporo-spatial presence of the target, the CD4 T cells 
induced by UV1 can provide a pro-immunological environment in the tumor and tumor-draining 
lymph node, continuously over time, regardless of the genetic makeup of the individual tumor 
cell. The vaccine mediated the CD4 immune response to optimize for priming of de novo 
immune responses (epitope spreading) and tumor cell killing in an otherwise highly dynamic 
tumor. 
UV1 is administered together with granulocyte-macrophage colony-stimulating factor 
(GM-CSF) as vaccine adjuvant. The GM-CSF used is sargramostim. Peptide-based vaccines 
generally are poorly immunogenetic due to their small size. Adjuvants provide “danger signals” 
for cells of the innate immune system to present vaccine epitopes in the context of major 
histocompatibility complex molecules, surface adherence molecules, and costimulatory 
molecules which are required for induction of a robust adaptive immune response. Sargramostim 
is selected as adjuvant for UV1 since it is documented to favor induction of peptide-specific 
Th11 immune responses after intradermal injections with peptides.24,25,26 UV1 vaccination refers 
to administration of both sargramostim and UV1.  
2.4 Clinical Data on UV1 Vaccination 
UV1 was brought into clinical development in 2013. Two dose-evaluation studies including 
40 patients with prostate cancer27 and non-small cell lung cancer (NSCLC)28 have completed 
treatment and patients are in follow-up for survival. One safety study combining UV1 
vaccination with ipilimumab in patients with melanoma has completed treatment of 12 patients. 
One safety study combining UV1 vaccination and pembrolizumab in patients with melanoma is 
ongoing for safety follow-up, with 30 patients enrolled and treated. A tabulated summary of 
completed, ongoing, and planned clinical studies is provided in Table 1.  
 
 

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Table 1 
Summary of Completed, Ongoing, and Planned Clinical Studies for UV1 
Vaccination 
As of November 2019, 72 patients have received UV1 vaccinations in the context of clinical 
trials, and of these 68 patients have completed the UV1 vaccination therapy. The completed 
studies have shown that UV1 is generally safe and well tolerated. Common adverse events (AEs) 
related to UV1 include pruritus, erythema, fatigue, diarrhoea, pain, and rash. Serious AEs were 
reported in 18% of the patients, and related SAEs in 10%. A few patients (7%) have reported 
serious allergic reactions to the UV1 vaccination. Four prostate cancer patients and 1 patient with 
metastatic malignant melanoma experienced serious allergic reactions occurring within 3 to 
30 minutes after injection of 9 or more doses of UV1 and sargramostim. All events resolved 
without sequelae.  
Protocol no. 
(EudraCT) 
/country 
Study design 
Study population Enrolled/ 
planned 
Dose and dosage regimen 
Completed studiesa) 
UV1/hTERT-
2012-L 
(2012-001852-
20)/ 
Norway 
Phase I/IIa open-
label, single-center 
dose-evaluation 
study of UV1 
Up to 10-year 
follow-up 
Locally advanced 
and/or metastatic 
NSCLC with 
stable disease after 
radiation and/or 
chemotherapy 
18 
Dose:  
UV1 100/300/700 µg, sargramostim 75 µg 
(intradermal injection) 
Week 1: Three UV1 vaccinations (D1, 3, 5) 
Weeks 2, 3, 4, 6, 8, 10, 14, 18, 22, 26: One 
UV1 vaccination 
From Week 39: UV1 vaccination every 
3 months up to Week 91 
UV1/hTERT-
2012-P 
(2012-002411-
26)/ 
Norway 
Phase I/IIa 
open-label, 
single-center dose-
evaluation study of 
UV1 
Up to 10-year 
follow-up 
Hormone-sensitive 
metastatic prostate 
cancer 
22 
Dose:  
UV1 100/300/700 µg, sargramostim 75 µg 
(intradermal injection) 
Week 1: Three UV1 vaccinations (D1, 3, 5) 
Weeks 2, 3, 4, 6, 8, 10, 14, 18, 22, 26: One 
UV1 vaccination 
From Week 52: UV1 vaccination every 
3 months up to Week 104 
UV1/hTERT-
MM 
(2013-005582-
39)/ 
Norway 
Phase I/IIa, 
open-label, 
single-center study 
of UV1 and 
ipilimumab 
Up to 10-year 
follow-up 
Unresectable or 
metastatic 
melanoma 
12 
Dose:  
UV1 300 µg, sargramostim 75 µg 
(intradermal injection) 
Ipilimumab according to label 
Week 1b): Three UV1 vaccinations (D1, 3, 5) 
Weeks 3, 4, 7, 10, 13, 17, 21: One UV1 
vaccination 
Weeks 2, 5, 8, 11: Ipilimumab 
Ongoing studies 
UV1/hTERT-
MM-103/ 
US 
Phase I open-label, 
multicenter study of 
UV1 and 
pembrolizumab 
2-year follow-up 
Unresectable or 
metastatic 
melanoma 
30/ 
30 
Dose: UV1 300 µg, sargramostim 37.5/75 µg 
(intradermal injection) 
Pembrolizumab according to label 
Week 1: Three UV1 vaccinations (D1, 3, 5) 
Weeks 2, 5, 8, 11, 14: One UV1 vaccination 
and pembrolizumab 
After Week 14: Pembrolizumab continued 
according to label 
a) Enrollment and UV1 treatment is completed and patients are in follow-up 
b) In the clinical study report, the first week of UV1 vaccination is referred to as “introduction week” and the week of first 
ipilimumab administration is “Week 1” 

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Across the three Phase I/IIa studies conducted with UV1 vaccination, vaccine-specific T cells 
were induced in 78% (range 67% to 91%) of the patients. This supports the universal utility of 
the vaccine across different individuals and cancer types, and thus pre-screening of patients for 
human leukocyte antigen-type or other biomarkers before treatment with UV1 is not needed.  
In the study investigating the use of the UV1 vaccine in combination with ipilimumab in 
metastatic malignant melanoma patients, UV1-specific immune responses were induced in 91% 
of the patients. The vaccine-specific T cells appeared more frequently and rapidly in this study 
than in the studies investigating patients with prostate cancer and late-stage NSCLC, suggesting 
a synergistic effect of blocking of CTLA-4 and vaccination with UV1. Nine patients were 
evaluable for tumor response according to RECIST 1.1. Of these, 3 patients obtained a partial 
response (PR) as best overall response, 3 achieved stable disease (SD), and 3 experienced 
progressive disease (PD). The median PFS was 6.5 months and the 3-year survival rate was 67% 
(8/12).  
The ongoing study combining UV1 and pembrolizumab in treatment of melanoma 
(UV1/hTERT-MM-103) has currently enrolled and treated 30 patients who are now in follow-up. 
Serious AEs and AEs of special interest (AESIs) are reported expedited to the sponsor and are 
the basis for the continuous safety assessment in this study. The collection of non-serious adverse 
is ongoing and will be reported when the study is completed, and all data have been finally 
verified. A thorough assessment of the safety profile of UV1 vaccination used in combination 
with pembrolizumab will include an evaluation of possible increase in frequency and severity of 
adverse reactions to pembrolizumab, the proportion of patients who have to terminate 
pembrolizumab treatment due to adverse reactions, and if the combination treatment enhances 
the UV1 related side effects.  
Up to the date of this protocol, the safety information available from study 
UV1/hTERT-MM-103 include nine serious adverse events (SAEs) for 7 patients (23.3%) in the 
study, the majority of which were considered unrelated to study treatment. One SAE of grade 3 
arthritis was assessed as possibly related to administration of UV1 vaccine and pembrolizumab, 
but the patient continued with treatment after resolution of the SAE. No AESIs (anaphylactic 
reaction, anaphylactic shock or hypersensitivity) have been reported among the patients. The 
number of UV1 vaccinations in this study is reduced to 8 compared to 12 to 18 in the completed 
Phase I studies as a measure to reduce the risk for serious allergic reactions following UV1 
vaccination treatment. 
Based on the currently available safety information, study UV1/hTERT-MM-103 has not 
revealed any immediate safety hazard for the use of UV1 vaccination as add-on to treatment to 
pembrolizumab for patients with malignant melanoma.  
Conclusion on the safety of UV1 vaccination in combination with checkpoint inhibitors 
With the safe treatment of 42 patients with UV1 vaccination in combination with either 
ipilimumab or pembrolizumab the safety of the product does not preclude continued clinical 
development of UV1 vaccination in combination with CTLA-4 inhibitors or PD-1/PD-L1 
inhibitors. 

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2.5 Rationale for Combination of UV1 with Checkpoint Inhibitors 
Checkpoint inhibition has become one of the main pillars in immune-based cancer therapies and 
involves inhibition of regulatory signalling pathways which normally reduces or modulates 
T cell activation in order to promote immune tolerance and suppress autoimmunity.29 Central to 
these processes are the CTLA-4 and PD-1 immune checkpoint pathways. These 2 pathways 
operate on different stages of an immune response. CTLA-4 mainly regulate activation of naïve 
T cells in the lymph nodes, and PD-1 regulates previously activated T cells at the later stages of 
an immune response, primarily in the peripheral tissue.30   
The mode of action of checkpoint inhibitors is to block the interaction between PD-1 and 
CTLA-4 expressed on T cells with their respective ligands, reducing negative effects on T cell 
activation and T effector mechanisms, and hence to promote T-cell-mediated immune activity.  
The immune checkpoint inhibitor ipilimumab is a monoclonal antibody specific for CTLA-4. 
The proposed mechanism of action for ipilimumab is the disruption of the interaction of CTLA-4 
which is expressed in the cell surface of naïve T cells following stimulatory signals, with B7 
co-stimulatory molecules (CD80 or CD86) expressed on antigen presenting cells.31 The result is 
inhibition of the down-modulatory function of CTLA-4, and hence potentiation of a 
T-cell-mediated immune response.32 Ipilimumab also interferes with the negative action of 
regulatory T-cells. The combined effect is a release of pre-existing immune responses and 
generation of a subsequent wave of secondary immune responses.  
Nivolumab is a monoclonal antibody specific for PD-1 which is expressed by T cells after 
persistent antigen exposure. PD-1 interacts with its ligands, PD-L1 and PD-L2, which is 
normally expressed on a range of different types of leucocytes, such as natural killer cells and 
macrophages and plays a role in modulation of immune system response. This interaction leads 
to inhibition of kinase-mediated signaling pathways, and thus, inhibition of T-cell activation and 
response. PD-L1 can be expressed on the surface of tumor cells as well and interaction between 
PD-1 on T cells and PD-L1 on tumor cells inhibits immune response against malignant cell. 
Blocking of the PD-1 receptor interaction with PD-L1 or PD-L2 reverses this immune 
suppression and releases T-cell effector function.  
Blockade of both CTLA-4 and PD-1 aims to induce proliferation of a higher number of T cells 
early in an immune response, and to restore immune responses of previously activated T cells 
that have become exhausted by chronic antigen stimulation. Combination therapy with 
nivolumab and ipilimumab in clinical studies has been shown to provide enhanced clinical 
benefit compared to single-agent therapy with either nivolumab or ipilimumab.  
Efficacy of the combined treatment of ipilimumab and nivolumab depends on the presence of a 
spontaneously induced T cell response against relevant tumor antigens. Patients who lack or have 
few tumor-specific T cells in their tumor are less likely to obtain durable benefit from 
combination therapy with nivolumab plus ipilimumab. UV1 vaccination has the potential to 
increase the efficacy of the combination therapy in patients where the immune response 
spontaneously primed by tumor antigens is insufficient for induction of long-term clinical 
benefit. Vaccination with UV1 amplifies the pool of hTERT specific tumor-reactive CD4 T cells 
from the naïve repertoire and has the potential to increase the breadth and diversity of the 

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tumor-reactive T cell response (epitope spread). Reciprocally, the efficacy of UV1 vaccination 
may be enhanced since the checkpoint inhibitors can augment the clonal expansion and effector 
activity of UV1-induced T cells that is otherwise restricted by intrinsic immune regulatory and 
tumor induced suppressor mechanisms. The addition of UV1 vaccination to checkpoint inhibitors 
thus have the potential to produce synergistic immunological activity which may transfer into 
increased clinical benefit compared to dual CTLA-4 and PD-1 checkpoint inhibitor therapy. 
2.6 Rationale for Dose and Administration Regimen 
Three Phase I/II studies investigating the use of UV1 vaccinations have been completed (n=52). 
One study in NSCLC and one study in prostate cancer were dose-finding studies comparing the 
safety of 100, 300, and 700 µg UV1 using 75 µg sargramostim per vaccination for up to 
18 vaccinations. No dose-limiting toxicities were observed in doses up to 700 µg. Signals of 
efficacy have been observed in all 3 studies in the form of vaccine-specific immune responses 
and PFS and OS which compares favorably to historical controls. 
Across the 3 completed Phase I/II studies with UV1 vaccination, 78% (40/51) of the patients 
with samples available for analysis had detectable vaccine-specific immune response. A higher 
proportion of patients with vaccine-specific immune response was seen in the group of patients 
receiving the 300 µg UV1 dose; 88% compared to 69% and 71% in the 100 and 700 µg groups, 
respectively. In the study where 300 µg UV1 was used in combination with ipilimumab in 
patients with melanoma, 91% of the patients showed an immune response to UV1.  
No clear dose relationship was observed in the proportion of patients experiencing AEs, although 
a tendency towards a lower frequency of related AEs, injection site events, and Grade 3 events 
was observed in the 300-µg dose group. Across the 3 studies, a total of 17 SAEs were reported, 
and 9 patients (17%) had related SAEs. Three patients had events that were related to 
ipilimumab, and 6 patients (12%) experienced 6 SAEs that were related to UV1 vaccination. Of 
these, 5 events in 5 patients (10%) were serious allergic reactions: anaphylactic reaction, 
anaphylactic shock, and hypersensitivity. Three events of serious allergic reactions occurred in 
the 700 µg UV1 dose group, 2 in the 300 µg UV1 dose group, and none in the 100 µg UV1 dose 
group. 
Taken together, the data on efficacy in terms of vaccine-specific immune response and safety 
related to dose of UV1 from the completed Phase I/II studies with UV1 support the use of the 
300 µg UV1 dose for further clinical development of UV1.  
Across the 3 completed Phase I/II studies, UV1 was administered with 75 µg of the adjuvant 
sargramostim per vaccination for up to 18 vaccinations. Localized dermal injection site reactions 
indicative of an inflammatory reaction to sargramostim and hence recruitment of dendritic cells 
to the injection site were seen in 63% of patients and 78% developed a vaccine-specific immune 
response. This supports the use of 75 μg sargramostim per UV1 vaccination for the further 
clinical development of UV1.  
To reduce the risk for serious allergic reactions to UV1 and/or sargramostim, the number of 
vaccinations with UV1 and sargramostim have been limited to 8 vaccinations over a period of 
73 days in the current protocol. The serious allergic reactions observed in 5 patients (10%) 

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occurred within 3 to 30 minutes after administration of the 9th or more vaccinations (>20 weeks 
of exposure). The immune response data from the completed study investigating the use of UV1 
with ipilimumab in patients with malignant melanoma support that 8 UV1 doses sufficed to 
generate a vaccine-specific immune response. The patients in that study received an average of 
5.5 UV1 vaccinations (range 3 to 9), and 91% of the evaluable patients had immune response 
within 12 weeks after first vaccination.  
In the current study, a dose of 75 µg sargramostim will be injected intradermally 10 to 
15 minutes prior to intradermal injection of UV1 at the same site.  
The 75 µg sargramostim dose is the same dose that has been used in the 3 completed Phase I/II 
studies with UV1 and in 10 out of 30 patients in the UV1/hTERT-MM-103 study.  
Patients in the experimental arm will receive 8 UV1 vaccinations over 4 cycles of nivolumab and 
ipilimumab. UV1 vaccination will be administered alone on Days 1, 3-7 (2 UV1 vaccinations 
within Day 3 to Day 7, consecutive dosing days not allowed) and 26, and in combination with 
nivolumab and ipilimumab on Days 10, 31, 52 and 73. The administration regimen for UV1 
vaccination during Days 1-10 is optimized for synergy with ipilimumab leading to effective 
priming and expansion of naïve hTERT specific T cells in the local lymph node draining the 
vaccine injection site. At Days 26 and 73, the UV1 vaccinations are optimized for re-activation 
and effector activity of the vaccine induced T cells in the tumor micro-environment in synergy 
with nivolumab and ipilimumab. 
The proposed vaccine administration regimen for study UV1 202 is similar to the vaccination 
regimen used in the Phase I studies UV1-hTERT-L (NSCLC), UV1-hTERT-P (prostate cancer) 
and UV1-hTER-MM (malignant melanoma) respectively. The Phase I administration regimen 
was based on animal studies of immune responses to peptide vaccines using sargramostim as 
adjuvant.24,25 It was documented that an intradermal co-administration regimen with 3 injections 
of the UV1 peptides with sargramostim during Week 1, followed by regular vaccinations is 
effective for induction of a vaccine-specific immune responses. This regimen aims to provide a 
gradient of sargramostim over time to attract Langerhans cells in the dermis to the vaccine 
injection site, allowing them to take up intact peptides while maturing into proper antigen 
presenting cells, migrate to the local lymph node and present the vaccine epitopes to naïve T cell, 
thereby priming vaccine-specific T cells.  
Since CTLA-4 is expressed on the cell surface of T cells within 72 hours of activation and will 
limit clonal expansion and induce G1 arrest of proliferating T cells.32,33 The first ipilimumab dose 
was administered subsequent to three initial UV1 vaccinations in study UV1-hTERT-MM. The 
following UV1 vaccinations were administered intermittent to the ipilimumab doses. UV1 
vaccination and ipilimumab administration was spaced in time to allow for CTLA-4 to be 
expressed in the cell membrane of clonally expanded T cells primed and activated by UV1 
vaccinations before blocking of the signaling through CTLA-4 with ipilimumab. The 
vaccine-specific immune response in study UV1-hTERT-MM appeared more frequently and 
rapidly than in the studies investigating the use of UV1 vaccination as monotherapy,27 supporting 
that ipilimumab act synergistically with UV1 to induce a vaccine-specific immune response. A 
similar regimen with spacing between UV1 vaccinations and administration of the first and 
second ipilimumab doses is proposed for the present study. 

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Nivolumab is administered every third week and will block signaling through PD-1 on 
tumor-specific T cells, thus releasing the effector activity of T cells activated by UV1 vaccination 
and T cells spontaneously activated by antigens in the tumor. The UV1 vaccinations at Days 52 
and 73 are administered concurrent with nivolumab and ipilimumab to optimize for boosting of 
an ongoing vaccine-specific immune response and release of effector activity of T cells in the 
tumor and draining lymph nodes. 
2.7 Rationale for Study Design 
Study UV1-202 is a randomized, multicenter, open-label, active-controlled clinical study to 
document the efficacy and safety of adding UV1 vaccination to dual checkpoint blockade 
therapy with nivolumab plus ipilimumab. 
Primary Endpoint 
Progression free survival is the primary endpoint of the study. In line with European Medicines 
Agency and FDA anticancer guidance, PFS is an acceptable primary endpoint in first-line 
metastatic disease, being reflective of clinical benefit. Progression free survival is considered an 
appropriate choice of endpoint especially when effective second-line therapies are available that 
would serve to confound subsequent OS outcome, as is the case in advanced malignant 
melanoma.  
Median PFS with nivolumab plus ipilimumab in unresectable or metastatic melanoma has been 
reported to be 11.5 months (95% CI, 8.9 to 16.5) in the nivolumab plus ipilimumab group.14 
Upon progression to more advanced melanoma, patients will likely receive subsequent effective 
anticancer treatment, including checkpoint monotherapy, chemotherapy, and targeted therapy, 
thus ruling out OS as a viable primary endpoint due to the diluting effect of these additional 
therapies.  
Progression free survival is appropriate for evaluating the effect of a therapeutic cancer vaccine. 
The expected mode of action for a therapeutic peptide cancer vaccine is to induce proliferation of 
T cells recognizing epitopes within the vaccine peptides. The secondary effects of these T cells 
will depend on the individual patient’s genetic, biochemical, and immunological status and may 
include increased frequency of tumor responses (increased ORR), prolonged DOR34, and 
increased frequency and duration of SD. Progression free survival, unlike DOR or ORR, as 
primary endpoints is suited to capture all tentative efficacy attributes of the vaccine. The study is 
therefore formally powered for analysis of PFS. Overall survival will be analyzed as supportive 
evidence. 
Treatment Arms 
UV1-202 is a randomized study with 2 arms, with the objective of documenting the add-on effect 
of UV1 vaccination to nivolumab and ipilimumab: 
• Experimental arm: UV1 vaccination in combination with nivolumab and ipilimumab 
• Control arm: nivolumab and ipilimumab 

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A 2-armed study will provide data on the efficacy and safety of UV1 vaccination as add-on to 
nivolumab and ipilimumab in patients with unresectable stage IIIB-D or unresectable metastatic 
melanoma which will suffice for hypothesis generation. 
In addition to the 2-armed part of the study, 20 patients will be enrolled in a single arm UV1 
cohort for collection of additional biological material to support the Extended Exploratory 
Cohort of the study. The single arm UV1 cohort is intended for exploratory purposes only 
(Appendix 7 Single Arm UV1 Cohort). 
2.8 Benefit/Risk Assessment 
The clinical studies completed to date (n=52) have demonstrated that UV1 vaccination is 
generally well tolerated, both as monotherapy and in combination with ipilimumab. There were 
no dose-limiting toxicities observed in the 2 dose-finding studies completed, and no apparent 
dose relationships in the rate of patients experiencing the most common related AEs (injection 
site related AEs). Anaphylactic reaction, anaphylactic shock, and hypersensitivity have been 
identified as AESIs for UV1 vaccination based on 5 events in 5 patients included in the 
completed studies.  
Study UV1/hTERT-MM-103, investigating the use of UV1 in combination with the anti-PD-1 
monoclonal antibody pembrolizumab, is currently ongoing for follow-up. 30 patients have been 
included and treated with UV1 and pembrolizumab. The combination of pembrolizumab and 
UV1 appears to be generally well tolerated. Nine serious adverse events (SAEs) for 7 patients 
(23.3%) in the study, the majority of which were considered unrelated to study treatment. 
To reduce the risk for AESIs, a maximum of 8 UV1 vaccinations will be administered to the 
patients under the current protocol. Patients will remain at the study site for observation for at 
least 4 hours after each UV1 vaccination. Patients who develop serious allergic reactions during 
treatment with UV1 vaccinations will be discontinued from further UV1 vaccinations.  
No information on the effects of UV1 vaccination on fertility and reproduction is available, and 
patients of childbearing potential must agree to use an adequate method of contraception prior, 
during, and after completion of treatment with UV1 vaccination. 
Nivolumab and ipilimumab are approved for the patient population suggested in the current 
study, and the toxicity profile of the combination is well characterized. The toxicities reported in 
the studies investigating the use of UV1 vaccination in combination with single agent 
ipilimumab and single agent pembrolizumab in malignant melanoma have so far been modest. 
Since the use of UV1 vaccination combined with nivolumab and ipilimumab has not been 
investigated previously, the protocol specifies specific safety monitoring for the study. 
The UV1 vaccine induces vaccine-specific CD4 T cell response in the majority of patients across 
indications. The immunogenicity of the peptides in UV1 is further supported by data from 
several long-term surviving patients with pancreatic cancer, lung cancer, and malignant 
melanoma treated with an earlier hTERT vaccine.28,29 The available clinical data on efficacy and 
reported AEs versus exposure from the completed and ongoing studies with UV1 indicates a 
favorable risk/benefit profile for UV1 vaccination. The underlying scientific rationale for 

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expected immunological synergy the use of UV1 vaccination in combination with nivolumab and 
ipilimumab justifies the present clinical study. 

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3 Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• 
To compare progression free survival (PFS) of 
UV1 vaccination* in combination with 
nivolumab and ipilimumab to that of nivolumab 
and ipilimumab  
Primary 
• 
PFS per Response Evaluation Criteria in 
Solid Tumors (RECIST) 1.1 
Time from randomization to progressive 
disease (PD) or death from any cause 
Secondary 
• 
To compare overall survival (OS) of UV1 
vaccination in combination with nivolumab and 
ipilimumab to that of nivolumab and ipilimumab  
Secondary 
• 
OS 
Time from randomization to death from 
any cause 
• 
To compare the objective response rate (ORR) of 
UV1 vaccination in combination with nivolumab 
and ipilimumab to that of nivolumab and 
ipilimumab  
• 
ORR per RECIST 1.1  
Proportion of patients with a best response 
of complete response (CR) or partial 
response (PR) 
• 
To compare duration of response (DOR) of UV1 
vaccination in combination with nivolumab and 
ipilimumab to that of nivolumab and ipilimumab  
• 
DOR per RECIST 1.1  
Time from first CR or PR to PD or death 
from any cause  
• 
To compare the safety of UV1 vaccination in 
combination with nivolumab and ipilimumab to 
that of nivolumab and ipilimumab  
• 
Adverse events (AEs), deaths, vital signs, 
laboratory assessments, and Eastern 
Cooperative Oncology Group (ECOG) 
performance status 
Exploratory 
• 
To elucidate the immunological mechanisms 
underlying the interplay between immune 
activation provoked by UV1 vaccination and 
inhibition of tumor resistance mechanisms and 
peripheral immune tolerance induced by 
checkpoint blockade, and how biological factors 
affect the efficacy of the combination therapy 
Exploratory 
• 
Change in immune- and tumor-related 
gene, cell, and protein profiles in blood 
over time in both treatment arms (analysis 
of plasma proteins, cell-free plasma DNA, 
and cellular genomic DNA).  
Other endpoints related to analysis 
conducted on biological material collected 
from the Extended Exploratory Cohort 
(refer to Appendix 2). 
*UV1 vaccination includes sargramostim, used as a vaccine adjuvant, and UV1 
 
 

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4 Study Design 
4.1 Overall Design 
This is a randomized, open-label, active-controlled, multicenter study to investigate efficacy and 
safety of UV1 vaccination in combination with nivolumab and ipilimumab as first-line treatment 
of adult patients (≥18 years) with histologically confirmed unresectable metastatic melanoma. 
The study is planned to be conducted at 40 study sites in Europe (approximately 16 sites) and the 
United States (approximately 24 sites). 
This study will consist of 3 phases: Screening, Induction period, and Follow-up period. The 
Follow-up period includes safety, response, and survival follow-up visits. 
After a Screening period of up to 28 days, eligible patients will be randomized in a 1:1 ratio to 
receive induction therapy: UV1 vaccination in combination with nivolumab and ipilimumab in 
an experimental arm, or nivolumab and ipilimumab in a control arm. Randomization can occur 
after all Screening procedures have been completed (up to 3 days [from Day -3 until Day 1] prior 
to first dosing on Day 1) and eligibility has been confirmed. It is estimated that approximately 
200 patients will need to be screened in order to randomize the required 154 patients. 
Patients in the experimental arm will receive 8 UV1 vaccinations over 4 cycles of nivolumab and 
ipilimumab. UV1 vaccination will be administered alone on Days 1, 3 to 7 (2 UV1 vaccinations 
within Day 3 to Day 7; consecutive dosing days not allowed), and 26, and in combination with 
nivolumab and ipilimumab on Days 10, 31, 52, and 73. 
Patients in the control arm will receive 4 cycles of nivolumab and ipilimumab on Days 1, 22, 43, 
and 64. 
Patients in both arms will start maintenance therapy 6 weeks after the last dose of induction 
therapy. The maintenance therapy is nivolumab at a dose of 480 mg every 4 weeks (Q4W) 
according to the label. It is not allowed to use any other dose of maintenance therapy (eg, 240 mg 
Q2W).  
The study is event driven. The primary and secondary endpoints will be analyzed at the earliest 
of either 70 PFS events reached across both treatment arms or 18 months post last patient 
randomized, at which time the sponsor will notify the sites. From the PFS cut-off date, patients 
will be followed for a further 24 months for additional survival data; further analyses of OS data 
will be performed until defined end of study to provide evidence supportive of PFS.   
All patients will be followed up until death or until the end of the study (EOS), whichever comes 
first. Estimated timelines at start of the study are outlined in Figure 1. 
 
 
 

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Figure 1 
Estimated Timelines 
First Patient In 
 
Last Patient In 
70 PFS events reached 
 
End of Study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
0 months 
 
15 months 
27 months 
 
51 months 
The estimated enrollment period is 15 months; the estimated time from last randomization to 70 
PFS events reached is 12 months; the estimated time from 70 PFS events to EOS is 24 months 
and the total study duration is estimated to be 51 months from first patient in. 
The study design and treatment are outlined in Figure 2.  
Figure 2 
Study Design 
 
 
 
 
 
 
 
 
 
 
The UV1 vaccination includes sargramostim, used as a vaccine adjuvant, at a dose of 75 µg and 
UV1 at a dose of 300 µg. Nivolumab and ipilimumab are dosed according to label in both 
treatment arms: induction therapy of nivolumab (1 mg/kg Q3W) and ipilimumab (3 mg/kg 
Q3W), and maintenance therapy of nivolumab (480 mg Q4W). 
Sargramostim and UV1 should be administered intradermally and injected at the same 
injection site (McBurney’s point) each time, located 1/3 of the distance from the anterior 
superior iliac spine to the umbilicus on the right side of the abdomen (or corresponding spot on 
the left side in case of appendectomy scar). Sargramostim is administered 10 to 15 minutes prior 
to each UV1 injection. Nivolumab and ipilimumab are administered intravenously, starting at 
least 1 hour after the administration of UV1. 
Following the last dose of induction therapy, the patient will then enter the Follow-up period and 
perform a safety follow-up visit 30 days post last dose of induction therapy. 
Screening period  
 
 
    Induction period  
 
 
          Follow-up period  
 (Days -28 to -1) 
 
 
 
    (Days 1 to 73 / Days 1 to 64)  
                          (4 - 5 years) 
 
 
 
 
 
       
 
 
First-line 
unresectable IIIB-D 
or unresectable IV 
metastatic melanoma 
Experimental arm 
 
UV1 vaccination:  
Administered on Days 1, 3-7 (2 UV1 
vaccinations), 10, 26, 31, 52, and 73 
 
Nivolumab and ipilimumab:  
Administered on Days 10, 31, 52, and 
73 
All patients 
Safety follow-up 
Response follow-up 
Survival follow-up 
 
At the earliest of either 70 PFS 
events reached or 18 months 
post last patient randomized, 
all patients will be followed-
up for 2 years 
 
Nivolumab maintenance 
therapy (480 mg Q4W) 
according to label 
Rand 
1:1  
N = 154 
Control arm 
 
Nivolumab and ipilimumab:  
Administered on Days 1, 22, 43 and 64 

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Tumor assessment will be done locally at the study site using RECIST 1.1 and immune Response 
Evaluation Criteria in Solid Tumors (iRECIST) criteria. Tumor imaging will be performed within 
14 days prior to randomization and then on Week 12 and Week 19 post randomization. 
Subsequent response follow-up imaging will be performed every 8 weeks for 32 weeks and then 
every 12 weeks. Patients with PD per RECIST 1.1 will have a new scan 4 to 8 weeks later to 
confirm PD per iRECIST. Patients with immune unconfirmed PD per iRECIST (iUPD) will 
continue at the Investigator’s discretion, with tumor imaging and treatment per protocol until 
immune confirmed PD per iRECIST (iCPD), until 70 PFS events are reached or until 18 months 
post last patient randomized (whatever comes first). Patients with iCPD per iRECIST will be 
discontinued from treatment and will proceed into the survival follow-up phase and be contacted 
per phone (or, at the investigator’s discretion visit the hospital) every 12 weeks until the earliest 
of either 70 PFS events reached or 18 months post last patient randomized. From the PFS cut-off 
date, the survival follow-up will continue in all patients every 6 months for 2 years. 
To reduce bias in evaluation of the efficacy endpoints, tumor evaluation for the statistical 
analysis of the efficacy endpoints will be done by blinded independent central review (BICR) 
according to the RECIST 1.1 criteria. All images must be submitted to the central imaging 
vendor, but the results from the BICR will not be provided to the study site. Two independent 
radiologists will perform the central imaging review without knowledge of treatment 
assignments. If there are discrepancies between the 2 readers, a standardized procedure involving 
a third reviewer for adjudication will take place.  
From signing of the Informed Consent Form (ICF) until the first dose of induction therapy, only 
AEs/SAEs caused by study-specific procedures should be reported. Non-serious AEs should be 
reported from the first dose of induction therapy until 30 days after the last dose of induction 
therapy, or until new anticancer treatment is initiated (whichever comes first). All SAEs should 
be reported from the first dose of induction therapy until 70 PFS events are reached, until 18 
months post last patient randomized or until new anticancer treatment is initiated (whichever 
comes first). Adverse events and SAEs that are ongoing beyond the required reporting timelines 
shall be followed up locally per institutional practice until resolution or stabilization or the 
patient is lost to follow up.  
During the study, an Independent Data Monitoring Committee (IDMC) will monitor safety 
information to ensure patient safety (refer Section 8.2.1).  
Patients at selected sites will have the option to be included in the Extended Exploratory Cohort 
of the study (Appendix 2) provided that the cohort is still open for inclusion. This cohort of 
approximately 40 patients, randomized in a 1:1 ratio to either of the 2 treatment arms, will have 
additional sampling of blood, tissue, and feces for exploratory purposes (see Table 9 and 
Table 10). The biologic sampling will be in addition to blood samples planned for all patients in 
the study. Fecal samples will be collected in the Screening period while tumor biopsies 
(snap-frozen tissue and formalin fixated paraffin embedded tissue) will be harvested in the 
Screening period and at the safety follow-up visit. In the experimental arm, delayed-type 
hypersensitivity (DTH) response will be assessed at 5 timepoints during the study. A biobank 
will be established for current and future analysis of the samples collected. 

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In addition to the 2-armed part of the study, 20 patients will be enrolled in a single arm UV1 
cohort for collection of additional biological material to support the Extended Exploratory 
Cohort of the study. The single arm UV1 cohort is intended for exploratory purposes only 
(Appendix 7 Single Arm UV1 Cohort). 
Planned Timelines 
First patient in: 
 
 
 
 
 
Q2 2020 
Last patient in:  
 
 
 
 
 
H1 2022 
Primary endpoint read out: 
 
 
 
 
H1 2024 
End of study:   
 
 
 
 
 
H1 2026 
The First Patient In is defined as the timepoint when the first patient is randomized.  
4.2 Measures to Minimize Bias: Randomization and Blinding 
Patients who satisfy all eligibility criteria will be randomly assigned by the central interactive 
web response system (IWRS; or equivalent) to receive induction therapy as either UV1 
vaccination in combination with nivolumab and ipilimumab in the experimental arm, or 
nivolumab and ipilimumab in the control arm. Randomization will be at a 1:1 ratio between the 
2 treatment arms.  
Randomization will be done by the IWRS provider using a validated software. Randomization 
can occur after all Screening procedures have been completed (up to 3 days [from Day -3 until 
Day 1] prior to first dosing on Day 1) and eligibility has been confirmed, to prevent the 
Investigator’s knowledge of treatment allocation influencing the decision to include the patient. 
Given the study design, with visits occurring at different timepoints in the 2 treatment arms, 
neither patients nor Investigators will be blinded to the study treatment arms. To limit bias in 
evaluation of the efficacy endpoints, the statistical efficacy analyses will be based on tumor 
assessments by BICR. 
Patients in the single arm UV1 cohort will not be randomized and will therefore not be included 
in the data used for analysis of primary and secondary endpoints.  
 

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5 Study Population 
The study population will consist of male and female patients at least 18 years of age with a 
histologically confirmed diagnosis of unresectable stage IIIB-D or unresectable stage IV 
metastatic melanoma. Patients must provide written consent and meet all the inclusion criteria 
and none of the exclusion criteria. 
Prospective approval of protocol deviations to the inclusion criteria, also known as protocol 
waivers or exemptions, will not be given. 
5.1 Inclusion Criteria 
To be eligible for randomization all of the following criteria must be met: 
Age and Sex 
1. Male or female patient at least 18 years of age at the time of signing the ICF. 
Type of Patient and Disease Characteristics 
2. Histologically confirmed diagnosis of unresectable stage IIIB-D or unresectable stage IV 
malignant melanoma. Patient must have at least 1 measurable lesion at Screening 
according to the RECIST 1.1 criteria. 
Note that lesions not measurable on a computed tomography (CT) scan or a magnetic 
resonance imaging (MRI) will be considered as non-measurable lesions. 
3. Eligible for combination treatment with nivolumab and ipilimumab. 
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 
5. Adequate organ function as indicated by the following laboratory values: 
Hematological 
a. Absolute neutrophil count (ANC) ≥1,500/µL 
b. Platelet count ≥100 x 103/µL 
c. Hemoglobin ≥9 g/dL or ≥5.6 mmol/L 
Renal 
d. Creatinine ≤1.5 x upper limit of normal (ULN) 
Hepatic 
e. Total bilirubin ≤1.5 x ULN or  
direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 ULN 
f. Aspartate aminotransferase/glutamic-oxaloacetic transaminase and alanine 
aminotransferase/glutamic-pyruvic transaminase ≤2.5 x ULN for patients without 
liver metastasis or ≤5 x ULN for patients with liver metastasis. 

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Male Patients: 
6. Male patients who are sexually active with a female of childbearing potential must agree 
to use an adequate method of contraception prior to the first dose through 5 months after 
the last dose of UV1 vaccination, nivolumab, or ipilimumab, whichever is administered 
last. The recommended method is using a male condom. 
Female Patients: 
7. Women of childbearing potential (WOCBP) must have a negative urine or serum/plasma 
pregnancy test. If the urine test is positive or cannot be confirmed as negative, a 
serum/plasma pregnancy test will be performed. The serum/plasma pregnancy test must 
be negative for the patient to be eligible. 
8. WOCBP (refer to Section 8.3.6) must use adequate contraception Adequate contraception 
must be maintained throughout the study, starting with the first dose through 5 months 
after the last dose of UV1 vaccination, nivolumab, or ipilimumab, whichever is 
administered last. The acceptable contraceptive methods for WOCBP included in the 
study are: 
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal 
contraception associated with inhibition of ovulation (oral, injectable, or implantable), 
Intrauterine device (IUD), Intrauterine hormone-releasing system (IUS), bilateral tubal 
occlusion, vasectomized partner (provided that the partner is the sole sexual partner of the 
WOCBP trial participant and that the vasectomized partner has received medical 
assessment of the surgical success), or sexual abstinence (if this is the preferred and usual 
lifestyle of the subject)  
Informed Consent 
9. Written informed consent prior to any study-specific procedures. 
5.2 Exclusion Criteria 
Patients are not eligible for randomization if any of the following criteria are met: 
Medical Conditions 
1. Previous non-melanoma malignancies unless curatively treated and complete remission 
was achieved at least 2 years prior to randomization. Patients with prior curatively-treated 
basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or 
carcinoma in situ of the breast, or other in situ cancers are allowed irrespective of time 
passed since curative treatment. Patients with prior completely resected malignant 
melanoma are also allowed. 
2. Known brain metastases or leptomeningeal metastases. If a patient experiences 
neurological symptoms indicative of brain metastases, a brain MRI should be performed. 
3. Diagnosis of uveal or ocular melanoma. 

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4. Known history or any evidence of active, non-infectious pneumonitis. 
5. History of New York Heart Association class 3-4 congestive heart failure or history of 
myocardial infarction within 6 months of starting study treatment. 
6. Active infection requiring systemic treatment. 
7. Diagnosis of immunodeficiency. 
8. Known history of severe hypersensitivity reactions to nivolumab, ipilimumab, 
sargramostim, or their excipients. 
9. Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies). No HIV 
testing is required unless mandated by local health authority. 
10. History of or active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C 
(hepatitis C virus antibody). Testing must be performed to determine eligibility. 
11. Women who are breastfeeding. 
Prior/Concomitant Therapy – Also Prohibited During the Induction Therapy 
12. Prior systemic treatment for unresectable stage IIIB-D or unresectable stage IV malignant 
melanoma. Prior systemic BRAF/MEK inhibitors or immunotherapy as neoadjuvant or 
adjuvant or other setting treatment of stage I-IIIA, resectable IIIB-D, or resectable IV if 
patient progressed earlier than 6 months after last dose of such treatment.   
13. Systemic corticosteroid treatment (doses exceeding 10 mg daily of prednisone or 
equivalent) or any other form of immunosuppressive treatment within 7 days prior to the 
first dose of induction therapy. Topical, ocular, intra-articular, intranasal, and inhalational 
corticosteroids (with minimal systemic absorption) are allowed. Physiologic replacement 
doses of systemic corticosteroids, a brief course of corticosteroids for prophylaxis (eg, 
contrast dye allergy) or for treatment of non-autoimmune conditions is permitted even 
with >10 mg/day prednisone equivalents. 
14. Receipt of a live vaccine within 30 days prior to the start of induction therapy. 
Prior/Concurrent Clinical Study Experience 
15. Receipt of any other investigational therapy within 4 weeks of the first dose of study 
treatment. 
Other Exclusions 
16. Any medical, psychological, or social condition that would make it difficult for the patient 
to participate in the study and comply with the study procedures, restrictions, and 
requirements. 
 

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6 Treatments 
6.1 Study Drugs 
Table 2 
Study Drugs (Induction Period) 
 
Investigational Medicinal Products 
Non-Investigational Medicinal Products 
Study drug name: 
Sargramostim 
UV1 
Nivolumab 
Ipilimumab 
Dosage Formulation: 
Reconstituted for 
injection 
Reconstituted for 
injection 
Reconstituted 
according to the 
prescribing 
information 
Reconstituted 
according to the 
prescribing 
information 
Dose Strengths/ Dosage 
Levels: 
75 µg 
300 µg 
1 mg/kg 
3 mg/kg 
Route of 
Administration: 
Intradermal injection 
Intradermal injection 
Intravenous infusion 
Intravenous infusion 
Dosing Instructions: 
75 µg administrated in a 
volume of 150 µL 
300 μg administered 
in a volume of 100 μL 
1 mg/kg according to 
the prescribing 
information 
3 mg/kg according to 
the prescribing 
information 
Packaging and Labeling: 
Lyophilized 
sargramostim provided 
in a glass vial. 
 
Labelled according to 
GCP/GMP and local 
regulations 
Lyophilized UV1 
provided in a glass 
vial.  
 
 
Labelled according to 
GCP/GMP and local 
regulations 
According to the 
prescribing 
information 
According to the 
prescribing 
information 
Storage conditions: 
Lyophilized: 
2ºC to 8ºC 
 
Reconstituted: 
2ºC to 8ºC  
(maximum 6 hours) 
Do not freeze or shake 
Lyophilized: 
2ºC to 8ºC 
 
Reconstituted: 
2ºC to 8ºC  
(maximum 6 hours) 
According to the 
prescribing 
information 
According to the 
prescribing 
information 
Manufacturer: 
Partner Therapeutics, 
Inc. 
Corden Pharma SpA 
Bristol-Myers Squibb 
Bristol-Myers Squibb 
Abbreviations: GCP = Good Clinical Practice; GMP = Good Manufacturing Practice; N/A = not applicable.  
6.1.1 
Sargramostim 
Sargramostim will be used as an adjuvant to UV1 in this study.  
Lyophilized sargramostim vials must be stored refrigerated (2°C to 8°C) and protected from 
light.  
Lyophilized sargramostim (250 µg) should be reconstituted with 0.5 mL water for injection to a 
concentration equal to 500 µg/mL giving a clear liquid ready for use. The volume to be 
administered is 150 μL, giving a dose of 75 μg. See also Table 3.  
Reconstituted sargramostim must be stored at 2ºC to 8ºC for a maximum of 6 hours prior to 
administration. Discard unused portion of reconstituted sargramostim. 

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Table 3 
Instructions for Preparation of Sargramostim 
Dose of Sargramostim 
per injection 
Package Format 
Content 
Water  
Concentration 
Volume 
injected 
75 µg 
Lyophilized sargramostim 
glass vial 
250 µg 
0.5 mL 
500 µg/mL 
150 µL 
Sargramostim is not approved as a vaccine adjuvant to UV1 and is considered an investigational 
medicinal product (IMP) in this study. 
6.1.2 
UV1 
UV1 is produced by lyophilization of a sterile aqueous solution of drug substances. No 
additional excipients are present in the UV1 product.  
Lyophilized UV1 vials must be stored refrigerated (2°C to 8°C) and protected from light. The 
vials may also be stored at room temperature (≤27ºC) for a maximum of 3 days to cover 
short-term excursions.  
Lyophilized UV1 (0.9 mg) should be reconstituted with 0.3 mL water for injection to a 
concentration equal to 3.0 mg/mL giving a clear liquid ready for use. The volume to be 
administered is 100 μL, giving a dose of 300 μg. See also Table 4.  
Reconstituted UV1 must be stored at 2°C to 8ºC for a maximum of 6 hours prior to 
administration. Excursions up to room temperature (≤27ºC) are allowed for a maximum of 
1 hour in total. Unused portion of reconstituted UV1 should be discarded.  
Table 4 
Instructions for Preparation of UV1 
Dose of UV1 per 
injection 
Package Format 
Content 
Water  
Concentration 
Volume 
injected 
300 µg 
Lyophilized UV1 
glass vial 
0.9 mg 
0.30 mL 
3.0 mg/mL 
100 µL 
UV1 is not approved as a therapeutic cancer vaccine and is considered an IMP in this study. 
6.1.2.1 
UV1 Used for Delayed-type Hypersensitivity Testing 
For patients who are participating in the Extended Exploratory Cohort, and who are randomized 
to the experimental arm, a DTH skin test will be performed as described in Appendix 2 and at 
timepoints described in Table 9.  
For the DTH testing, 20 μL of the reconstituted UV1 solution should be injected (intradermally) 
without sargramostim in the skin of the anterior forearm. For the visits where both UV1 
vaccination and DTH testing are performed, the UV1 solution prepared for the vaccination 

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should also be used for the DTH testing. The injection for the DTH testing should be done prior 
to the UV1 vaccination.  
6.1.3 
Nivolumab 
Nivolumab will be reconstituted according to the prescribing information/product characteristic. 
Patients will receive an induction therapy dose of 1 mg/kg, administered intravenously. 
Six weeks following the last dose of induction therapy, patients will receive maintenance therapy 
at a dose of 480 mg Q4W according to the label. It is not allowed to use any other dose of 
maintenance therapy (eg, 240 mg Q2W).  
Nivolumab is to be used according to the prescribing information and is a non-investigational 
medicinal product (NIMP) in this study. 
6.1.4 
Ipilimumab 
Ipilimumab will be reconstituted according to the prescribing information. Patients will receive 
an induction therapy dose of 3 mg/kg, administered intravenously. 
Ipilimumab is to be used according to the prescribing information and is a NIMP in this study. 
6.1.5 
Administration of Study Drugs 
The administration of study drugs should be done as the last procedure at each applicable study 
visit per the schedule of activities (Table 5 and Table 6). 
Sargramostim and UV1 should be administered intradermally in an area corresponding to 
McBurney’s point (Figure 3) on the right side of the abdomen (or corresponding spot on the left 
side in case of appendectomy scar). It is important that both injections are strictly intradermal. 
The utmost care must be taken so no material is administered subcutaneously. When done 
correctly, a small bleb should appear following the injection. An injection too superficial will 
result in loss of volume from the injection site during injection or after withdrawal of the needle. 
All 16 injections (8 sargramostim and 8 UV1) should be injected at the exact same site. 
Permanent marker-pens may be used to ensure that the same site is utilized each time. 

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Figure 3 
McBurney’s Point 
 
Administration of UV1 should be done 10 to 15 minutes after the administration of 
sargramostim. The UV1 is to be administrated at the exact same site as the sargramostim.  
Allergic reactions may occur after sargramostim and UV1 injections. Therefore, patients should 
remain at the site for observation for at least 4 hours after each UV1 injection. 
Nivolumab and ipilimumab are administered intravenously according to the label and 
administration is to be started at least 1 hour after the injection of UV1. 
Patients in the experimental arm will receive 8 UV1 vaccinations over 4 cycles of nivolumab and 
ipilimumab. The UV1 vaccination will be administered alone on Days 1, 3 to 7 (2 UV1 
vaccinations), and 26, and in combination with nivolumab and ipilimumab on Days 10, 31, 52, 
and 73. 
Patients in the control arm will receive 4 cycles of nivolumab and ipilimumab, on Days 1, 22, 43, 
and 64. 
The administration of sargramostim, UV1, nivolumab, and ipilimumab must be recorded in the 
patients’ medical files and the appropriate section of the electronic Case Report Form (eCRF). 
The reason for dose interruption, reduction, or omission will also be recorded in the medical files 
of patient and later in the eCRF. This information will be used to assess compliance with 
treatment. 
Following the induction therapy, patients in both treatment arms will start maintenance therapy 
and receive nivolumab at a dose of 480 mg Q4W according to the label. It is not allowed to use 
any other dose of maintenance therapy (eg, 240 mg Q2W). Nivolumab is the standard of care and 
should be monitored according to the institutional practice (including routine blood sampling). 
6.1.6 
Preparation/Handling/Storage/Accountability 
Unless stated otherwise, sargramostim, nivolumab, and ipilimumab should be stored and handled 
according to the prescribing information. All handling of study drug should be compliant with 
normal handling of sterile products for injection. 

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UV1 and sargramostim will be supplied to the study sites by the Sponsor. Nivolumab and 
ipilimumab will be sourced locally by the study sites. 
The Investigator or designee must maintain accurate records of study drugs received from the 
Sponsor, and documentation of preparation and administration of sargramostim, UV1, 
nivolumab, and ipilimumab. Drug name, dose, and batch number/study treatment ID (if required) 
will be documented for all study drugs administered. 
Only patients randomized in the study may receive study drug and only site staff authorized by 
the Investigator may supply or administer the study drug(s). All study drugs must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area with access 
limited to the Investigator and authorized site staff. 
The Investigator or designee must maintain a log to confirm appropriate temperature conditions 
have been maintained during storage for all study drugs received by the Sponsor and any 
discrepancies must be reported and resolved before use of the study drug. 
The Investigator or designee is responsible for study drug accountability, reconciliation, and 
record maintenance (ie, receipt, reconciliation, and final disposition records). 
Where appropriate facilities and procedures for drug destruction exist and prior approval from 
the site monitor has been received, site personnel will account for appropriate destruction. 
6.1.7 
Treatment of Allergic Reactions to UV1 Vaccination 
Investigators are advised to follow the standard treatment of anaphylaxis and allergies per local 
guidelines.  
6.1.8 
Dose Modification 
Dose modification of sargramostim or UV1 is not allowed in this study. Nivolumab and 
ipilimumab should be dosed according to the label.  
6.1.9 
Overdose 
There is no information on overdose of UV1 vaccination, but the distribution route and 
degradation of the UV1 vaccination suggests that there would be few consequences, if any. 
Therefore, in the event of an overdose, the patient should be observed for any reactions and 
treated symptomatically. 
There is no information on overdose with ipilimumab and nivolumab, given either as 
monotherapies or concomitantly. In case of overdosage, patients must be closely monitored for 
signs or symptoms of adverse reactions and appropriate symptomatic treatment instituted. 

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6.2 Concomitant Medication 
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins, 
and/or herbal supplements) that the patient is receiving at the time of randomization or receives 
during the study must be recorded along with: 
• reason for use 
• dates of administration including start and end dates 
• dosage information including dose and frequency. 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
All ongoing and new medications will be recorded from 28 days prior to randomization, until 
30 days after the last dose of induction, or until new anticancer treatment is initiated (whichever 
comes first). Ongoing and new medications shall also be recorded in connection with any SAEs. 
6.2.1 
Prohibited Medications During Induction Period 
The following medications and vaccinations are not allowed during the Induction period: 
• Immunosuppressive agents  
• Systemic corticosteroids >10 mg daily prednisone equivalent (except as stated in 
Section 6.2.2) 
• Any concurrent anticancer therapy (ie, chemotherapy, hormonal therapy, immunotherapy, 
radiation therapy, or investigational agents for treatment of cancer). Radiation therapy to 
a symptomatic lesion may be allowed after consultation with the sponsor. Supportive care 
for disease-related symptoms, including bisphosphonates and denosumab, may be offered 
to all patients in the study. 
• Live vaccines within 30 days prior to the first dose of induction therapy and while 
participating in the study. Examples of live vaccines include, but are not limited to, 
measles, mumps, rubella, chicken pox, yellow fever, seasonal flu, H1N1 flu, rabies, BCG, 
and typhoid vaccine. 
• Other investigational agents. 
6.2.2 
Permitted Medications During Induction Period 
Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational 
corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic 
corticosteroids, a brief course of corticosteroids for prophylaxis (e.g. contrast dye allergy) or for 
treatment of non-autoimmune conditions is permitted even with >10 mg/day prednisone 
equivalents. 

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6.2.3 
New Anticancer Treatment 
Details of any new anticancer treatments, from the time of the last dose of induction therapy until 
the earliest of either 70 PFS events reached or 18 months post last patient randomized, must be 
recorded in the eCRF. The reason for end of treatment for IMP and NIMP (nivolumab and 
ipilimumab) must be recorded. 
6.3 Treatment After Progressive Disease 
Clinical evidence indicates that some patients treated with immune system-stimulating agents 
may develop PD by conventional response criteria (ie, pseudo-progression per iRECIST), before 
demonstrating clinical overall responses and/or SD. This may be explained by:  
• Enhanced inflammation within tumors leading to increased tumor size which would 
appear as an enlarged index lesion and as newly visible small non-index lesions. Over 
time, both the malignant and inflammatory portions of the mass may then decrease 
leading to overt signs of clinical improvement. 
• Initially, the kinetics of tumor growth may outpace anti-tumor immune activity. With 
sufficient time, the anti-tumor activity will dominate and become clinically apparent. 
For patients who have initial radiological evidence of PD by RECIST 1.1 or iUPD (per 
iRECIST), it is at the discretion of the Investigator to keep the patient on induction/maintenance 
therapy (in the absence of clinical deterioration) until repeat imaging is obtained 4 to 8 weeks 
afterwards (iRECIST-based management). The decision to continue induction/maintenance 
therapy should only be made if the patient is assessed to be clinically stable, deriving clinical 
benefit, and tolerating the treatment. 
At a minimum, patients must meet the following criteria for continuing induction/maintenance 
therapy after PD per RECIST 1.1/iUPD is identified: 
• Absence of worsening symptoms and signs (including worsening of laboratory values) 
• No decline in ECOG performance status 
• Absence of rapid PD or of progressive tumor at critical anatomical sites (eg, cord 
compression) requiring urgent alternative medical intervention. 
If repeat imaging fails to demonstrate iCPD (by iRECIST) and the patient continues to be 
clinically stable, induction/maintenance therapy should continue per protocol. 
If repeat imaging demonstrates iCPD, induction/maintenance therapy should be discontinued.  
The continuation/discontinuation of nivolumab as maintenance therapy will be recorded in the 
patients’ medical file and in the eCRF.  

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7 Study Duration and Schedule of Activities 
This study will consist of 3 phases: Screening, an Induction period, and a Follow-up period. The 
Follow-up period includes safety, response, and survival follow-up visits.  
 

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Table 5 
Schedule of Activities – Experimental Arm 
 
Screening 
Induction period 
Follow-up period 
Visit/Cycle 
 
V1 
 
V2 + 3 
 
V4 
C1 
V5 
 
V6 
C2 
V7 
C3 
V8 
C4 
Safety follow-
up 
Response follow-up 
 
Survival follow-upa 
 
Survival follow-
upa 
 
Visit window 
 
0 
0 
± 2d ± 2d ± 2d 
± 2d ± 2d 
+7d 
±1w 
±1w 
+2w 
Days/Weeks 
D -28 to -1 
D1 
D3-7 
D10 D26 D31 D52 
D73 
30 days post 
last dose of 
induction 
therapy 
10w post last dose of   
induction therapy 
then every 8w for 32w.  
Subsequent visits every 12w until 
iCPD per iRECIST or PFS cut-off 
date reached 
Every 12w from 
iCPD per iRECIST 
until PFS cut-off date 
reached 
From time of the 
PFS cut-off date 
reached:  
Every 6 months for 
2 years 
UV1 vaccinations 
Consecutive 
dosing days not 
allowed 
Signed consent  
X 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs & ECOG 
X 
X 
 
 
X 
 
X 
X 
X 
X 
 
 
 
Physical examination 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
Local lab analysis (all patients)b 
• Hematology & chemistrym 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
• Hepatitis B & C virus 
X 
 
 
 
 
 
 
 
 
 
 
 
 
• Pregnancy testc 
X 
 
 
 
X 
 
X 
X 
X 
X 
 
 
 
Central lab sampling (all 
patients)d 
 
X 
 
 
 
 
X 
X 
 
X 
X (2nd visit only) 
 
 
Randomizatione 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Treatment: 
• UV1 vaccination  
 
X 
X 
X 
X 
X 
X 
X 
X 
 
• Nivolumab  
 
 
 
 
X 
 
X 
X 
X 
Nivolumab 480 mg Q4W according to label (maintenance therapy)f 
• Ipilimumab 
 
 
 
 
X 
 
X 
X 
X 
 
Adverse Eventsg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant medicationh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Subsequent anticancer treatment 
 
 
 
 
 
 
 
 
 
X 
X 
X 
 
Survival status 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
Tumor imagingi 
FIRST tumor imaging during Screening at Day -14 to -1 
SECOND tumor imaging at Week 12 and THIRD tumor imaging at Week 19 post randomization 
SUBSEQUENT tumor imaging every 8 weeks for 32 weeks and then every 12 weeks until PD per iRECIST or until PFS cut-off date is reached (whichever comes first) 
ADDITIONAL tumor imaging if premature treatment discontinuation due to any cause 
Extended Exploratory Cohort (40 patients)j 
Signed consent (exploratory 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Fecal sample 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Tumor biopsy (FFPE & 
f
)k
X 
 
 
 
 
 
 
 
 
X 
 
 
 
DNA & SNP 
 
X 
 
 
 
 
 
 
 
 
 
 
 
PBMC 
 
X 
 
 
 
 
X 
 
 
X 
X (2nd visit only) 
 
 
DTHl 
 
X 
 
 
 
 
X 
X 
 
X 
X (2nd visit only) 
 
 

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Abbreviations: AE = adverse event; C = cycle; D/d = day; DNA = deoxyribonucleic acid; DTH = delayed-type hypersensitivity; ECOG = Eastern Cooperative Oncology Group; FFPE = formalin fixed, 
paraffin embedded; ICF = Informed Consent Form; iCPD = immune confirmed progressive disease; iRECIST = immune Response Evaluation Criteria in Solid Tumors; PFS = Progression Free 
Survival; PBMC = peripheral blood mononuclear cell; Q4W = every 4 weeks; SAE = serious adverse event; SNP = single nucleotide polymorphisms; V = visit; w = week. 
a Patients with iCPD per iRECIST will be discontinued from treatment and will proceed into the survival follow-up phase and be contacted per phone (or, at the Investigator’s discretion visit the 
hospital) every 12 weeks until PFS cut-off date is reached (earliest of either 70 PFS events or 18 months post last patient randomized). From the PFS cut-off date, the survival follow-up visits will 
continue every 6 months for 2 years.    
b Local lab analysis for verification of eligibility criteria is required during Screening at Day -14 to -1. See Table 7 for protocol-required safety laboratory assessments. 
c WOCBP require negative pregnancy test within 72 hours prior to randomization, at Days 10, 31,52, 73 and at the safety follow-up visit. Additional pregnancy tests according to local regulations for 
treatment of nivolumab and ipilimumab, if required.  
d See Table 8 for collection of samples for exploratory analysis.  
e Patients can be randomized up to 3 days (from Day -3 until Day 1) prior to first dosing on Day 1 but only after all Screening assessments are completed.   
f Patients will start maintenance therapy 6 weeks after last dose of induction therapy. 
g From signing of the ICF until the first dose of induction therapy only AEs/SAEs caused by study-specific procedures should be reported. All non-serious AEs should be reported from the first dose of 
induction therapy until 30 days after the last dose of induction therapy, or until new anticancer treatment is initiated (whichever comes first). All SAEs should be reported from the first dose of 
induction therapy until the PFS cut-off date is reached or until new anticancer treatment is initiated (whichever comes first).  
h All ongoing and new medications will be recorded from 28 days prior to randomization, until 30 days after the last dose of induction, or until new anticancer treatment is initiated (whichever comes 
first). Ongoing and new medications shall also be recorded in connection with any SAEs. 
i Tumor imaging should be performed regardless of treatment stop or delays and within a visit window of ± 7 days. Tumor imaging will be performed using CT/MRI scans of the chest, abdomen, and 
pelvis. CT scans are the required modality for measurable disease unless a patient has a clinical condition (e.g. severe contrast allergy) or the lesions are better visualized through the use of MRI. 
The same imaging technique has to be used in a patient throughout the study. If an unscheduled CT/MRI is performed during the study, subsequent protocol planned CTs/MRIs should be performed 
unless the time interval between the CTs/MRIs is <4 weeks.  
j A cohort of approximately 40 patients at selected sites will be asked to volunteer for additional biological sampling and analysis. See Table 9 and Table 10 for collection of samples and DTH for the 
Extended Exploratory Cohort. 
k If the patient has only one target lesion, the biopsy should be taken either subsequent or at least 7 days prior to the screening imaging scan. 
l UV1 without sargramostim injected intradermally in the skin of the anterior forearm. Patient will measure and record the skin reaction 48±4 hours after the injection.  
m It is recommended to have blood sampling on day of treatment. If the sampling was not done on the day of treatment and the most current Liver Function Test (LFT) results warrant a safety concern, 
the site must repeat the LFT panel on the day of treatment and review the results prior to study drug administration.  
 

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Table 6 
Schedule of Activities – Control Arm 
Extended Exploratory Cohort (40 patients)j 
Signed consent (exploratory cohort) 
X 
 
 
 
 
 
 
 
Fecal sample 
X 
 
 
 
 
 
 
 
Tumor biopsy (FFPE & snap-frozen) k 
X 
 
 
 
 
X 
 
 
DNA & SNP 
 
X 
 
 
 
 
 
 
PBMC 
 
X 
 
X 
 
X 
X (2nd visit only) 
 
 
Screening 
Induction therapy 
Follow-up period 
Visit/Cycle 
 
V1 
C1 
V2 
C2 
V3 
C3 
V4 
C4 
Safety 
follow-up  
Response follow-up 
Survival follow- upa 
 
Survival follow- upa 
 
Visit window 
0 
± 2d 
± 2d 
± 2d 
+7d 
±1w 
±1w 
+2w 
Days/Weeks 
D -28 to -1  
D1 
D22 
D43 
D64 
30 days post 
last dose of 
induction 
therapy 
10w post last dose of 
induction therapy  
then every 8w for 
32w. Subsequent 
visits every 12w until 
iCPD per iRECIST or 
PFS cut-off date 
reached 
Every 12w from iCPD per 
iRECIST  
until PFS cut-off date reached 
From time of thePFS cut-off date 
reached:  
Every 6 months for  
2 years 
Signed consent  
X 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
Vital signs & ECOG 
X 
X 
X 
X 
X 
X 
 
 
 
Physical examination 
X 
 
 
 
 
X 
 
 
 
Local lab analysis (all patients)b 
• Hematology & chemistryl) 
X 
X 
X 
X 
X 
X 
 
 
 
• Hepatitis B & C virus 
X 
 
 
 
 
 
 
 
 
• Pregnancy test c 
X 
X 
X 
X 
X 
X 
 
 
 
Central lab sampling (all patients)d 
 
X 
 
X 
X 
X 
X (2nd visit only) 
 
 
Randomizatione 
 
X 
 
 
 
 
 
 
 
Treatment: 
 
• Nivolumab  
 
X 
X 
X 
X 
Nivolumab 480 mg Q4W according to label (maintenance therapy)f 
• Ipilimumab 
 
X 
X 
X 
X 
 
Adverse Eventsg 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant medicationh 
X 
X 
X 
X 
X 
X 
 
 
 
Subsequent anticancer treatment 
 
 
 
 
 
X 
X 
X 
 
Survival status 
 
 
 
 
 
 
 
X 
X 
Tumor imagingi 
FIRST tumor imaging during Screening at Days -14 to -1 
SECOND tumor imaging at Week 12 and THIRD tumor imaging at Week 19 post randomization 
SUBSEQUENT tumor imaging every 8 weeks for 32 weeks and then every 12 weeks until PD per iRECIST or until the PFS cut-off date is reached (whichever comes 
first) 

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Abbreviations: AE = adverse event; C = cycle; D/d = day; DNA = deoxyribonucleic acid; ECOG = Eastern Cooperative Oncology Group; FFPE = formalin fixed, paraffin embedded; ICF = Informed 
Consent Form; iCPD = immune confirmed progressive disease; iRECIST = immune Response Evaluation Criteria in Solid Tumors; PFS = Progression Free Survival; PBMC = peripheral blood 
mononuclear cell; Q4W = every 4 weeks; SAE = serious adverse event; SNP = single nucleotide polymorphisms; V = visit; w = week. 
a Patients with iCPD per iRECIST will be discontinued from treatment and will proceed into the survival follow-up phase and be contacted per phone (or, at the Investigator’s discretion visit the 
hospital) every 12 weeks until PFS cut-off date is reached (earliest of either 70 PFS events or 18 months post last patient randomized). From the PFS cut-off date, the survival follow-up visits will 
continue every 6 months for 2 years.   
b Local lab analysis for verification of eligibility criteria is required during Screening at Day -14 to -1. See Table 7 for protocol-required safety laboratory assessments. 
c WOCBP require negative pregnancy test within 72 hours prior to randomization, at Days 1, 22, 43, 64 and at the safety follow-up visit. Additional pregnancy tests according to local regulations for 
treatment of nivolumab and ipilimumab, if required.  
d See Table 8 for collection of samples for exploratory analysis.  
e Patients can be randomized up to 3 days (from Day -3 until Day 1) prior to first dosing on Day 1 but only after all Screening assessments are completed.  
f Patients will start maintenance therapy 6 weeks after last dose of induction therapy. 
g From signing of the ICF until the first dose of induction therapy only AEs/SAEs caused by study-specific procedures should be reported. All non-serious AEs should be reported from the first dose of 
induction therapy until 30 days after the last dose of induction therapy, or until new anticancer treatment is initiated (whichever comes first). All SAEs should be reported from the first dose of 
induction therapy until the PFS cut-off date is reached or until new anticancer treatment is initiated (whichever comes first).  
h All ongoing and new medications will be recorded from 28 days prior to randomization, until 30 days after the last dose of induction, or until new anticancer treatment is initiated (whichever comes 
first). Ongoing and new medications shall also be recorded in connection with any SAEs. 
i Tumor imaging should be performed regardless of treatment stop or delays and within a visit window of ± 7 days. Tumor imaging will be performed using CT/MRI scans of the chest, abdomen, and 
pelvis. CT scans are the required modality for measurable disease unless a patient has a clinical condition (e.g. severe contrast allergy) or the lesions are better visualized through the use of MRI. 
The same imaging technique has to be used in a patient throughout the study. If an unscheduled CT/MRI is performed during the study, subsequent protocol planned CTs/MRIs should be performed 
unless the time interval between the CTs/MRIs is <4 weeks.  
j A cohort of approximately 40 patients at selected sites will be asked to volunteer for additional biological sampling and analysis. A separate ICF will be used for the Extended Exploratory Cohort and 
will be different than the main study. See Table 9 and Table 10 for collection of samples for the Extended Exploratory Cohort. 
k If the patient has only one target lesion, the biopsy should be taken either subsequent or at least 7 days prior to the screening imaging scan. 
l It is recommended to have blood sampling on day of treatment. If the sampling was not done on the day of treatment and the most current Liver Function Test (LFT) results warrant a safety concern, 
the site must repeat the LFT panel on the day of treatment and review the results prior to study drug administration.  
 
 
 
 
 

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7.1 Screening 
Within 28 days prior to randomization, potential patients will be evaluated to determine if they 
fulfill the eligibility criteria described in Section 5.1 and Section 5.2. Procedures conducted as 
part of the patient’s routine clinical management (eg, blood count) obtained before signing of the 
ICF may be utilized for Screening or Baseline purposes provided the procedure met the 
protocol-specified criteria and was performed within the timeframe defined in the schedule of 
activities (Table 5 and Table 6). 
7.1.1 
Screen Failures 
Screen failures are defined as patients who consent to participate in the clinical study but who are 
not subsequently randomized. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure patients to meet the consolidated standards of reporting 
trials publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demographics, screen failure details, eligibility criteria, and any AEs caused 
by study-specific procedures. 
Individuals who do not meet the criteria for randomization (screen failures) may be re-screened 
once. Re-screened patients should be assigned a new screening number and be re-consented. 
The Investigator must account for all patients screened and randomized. A patient participation 
log is to be completed with the patient’s screening number, randomization number (if patient is 
randomized), date of consent, and date of the initial administration of induction therapy. If a 
patient is not randomized, the reason for exclusion from the study will be documented in the 
eCRF. 
7.2 Induction Period  
Patients who satisfy all eligibility criteria will be randomized in a 1:1 ratio between the 
2 treatment arms and start treatment with induction therapy:   
• Experimental arm: UV1 vaccination in combination with nivolumab and ipilimumab 
• Control arm: nivolumab and ipilimumab. 
The combination of nivolumab and ipilimumab as induction therapy is administered Q3W for 
4 doses. Patients randomized to the experimental arm will undergo 4 additional visits to receive 
single doses with UV1 vaccination.  
7.2.1 
Discontinuation of Induction Therapy  
If, during the Induction period, both nivolumab and ipilimumab are temporarily discontinued for 
patients randomized to the experimental arm, study visits and treatment with UV1 vaccination 
should also be temporarily discontinued. However, UV1 vaccination at visit 5 (monotherapy) can 
be administered if the patient would have been considered eligible to receive nivolumab and 
ipilimumab at that time point. 

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If, during the Induction period, nivolumab and ipilimumab are permanently discontinued, study 
visits and treatment with UV1 vaccination should be permanently discontinued. If the decision to 
permanently discontinue induction therapy is done during a scheduled study visit, the procedures 
and assessments applicable for that visit should be performed. However, if it’s been > 30 days 
since last induction dose, the safety follow-up visit should be performed instead. If the decision 
to permanently discontinue induction therapy is done between two scheduled study visits, the 
next visit will be the safety follow-up visit which shall be performed 30-37 days after the last 
induction dose. If it’s been > 37 days since last induction dose, the safety follow-up visit should 
be performed as soon as possible. 
If the UV1 vaccination is discontinued, nivolumab and ipilimumab induction therapy may 
continue as scheduled in the protocol. With the exception of the DTH testing, all study 
procedures and assessments described in the schedule of activities will be performed. 
Discontinuation of induction therapy does not represent withdrawal from the study. All patients 
that permanently discontinue all induction therapies prior to completion of the Induction period 
(Days 1 to 73 in the experimental arm and Days 1 to 64 in the control arm) will attend the safety 
follow-up visit and continue in the study for the determination of PD and survival. 
UV1 vaccination will be discontinued if any of the following situations occur: 
1. Patient requests to stop UV1 vaccination, nivolumab and ipilimumab 
2. Any clinical AE, laboratory abnormality, intercurrent illness which, in the opinion of the 
Investigator, indicates that continuation with UV1 vaccination is not in the best interest of the 
patient 
3. Patient starts another anticancer treatment while receiving UV1 vaccination, nivolumab, and 
ipilimumab 
4. Pregnancy 
5. At the discretion of the Investigator 
6. Termination of the study by the Sponsor. 
Adverse events associated with nivolumab and/or ipilimumab and/or UV1 vaccine exposure may 
represent an immunologic etiology. These AEs may occur shortly after the first dose or several 
months after the last dose of treatment. Nivolumab and/or ipilimumab must be withheld for 
moderate or severe drug-related toxicities and severe or life-threatening AEs.  
Patients who develop serious allergic reactions during treatment with sargramostim and/or UV1 
will be discontinued from further vaccinations independently of the deemed relatedness to 
sargramostim or UV1. Treatment with nivolumab and ipilimumab may continue at the 
Investigator’s discretion. 
Permanent Discontinuation of Induction Therapy Due to Safety Reasons  
If due to safety reasons, all induction therapies are discontinued, the patient will complete the 
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patient will continue with the response follow-up visits (10 weeks post last dose of induction 
therapy).  
Permanent Discontinuation of Induction Therapy Due to Progressive Disease  
If, during the Induction period, a patient has PD confirmed by a repeat CT/MRI scan according 
to iRECIST (iCPD), all induction therapy will be discontinued and the patient will complete the 
safety follow-up visit 30 to 37 days after the last dose of induction therapy. Further anticancer 
treatment will be given at the Investigator’s discretion. If anticancer treatments other than 
nivolumab are planned to start prior to 30 days after the last dose of induction therapy, the safety 
follow-up visit will be performed as soon as possible following the confirmed PD. The patient 
will thereafter continue into the survival follow-up. 
Permanent Discontinuation of Induction Therapy Due or Patient Decision or Investigator’s 
Discretion 
Patients taking part in the study can request to stop treatment with all induction therapies or 
decision to stop can be done at the Investigator’s discretion. If either occurs, the patient will be 
asked to complete the safety follow-up visit 30 to 37 days after the last dose of induction therapy. 
The patient should be encouraged to continue the study as scheduled thereafter. If this is not 
accepted by the patient, he/she should be asked for acceptance to continue in the survival 
follow-up and be contacted by phone (or, at the investigator’s discretion visit the hospital).  
7.3 Follow-up Period 
Six weeks after last dose of induction therapy, patients in both treatment arms will start 
maintenance therapy and receive nivolumab at a dose of 480 mg Q4W according to the label. It 
is not allowed to use any other dose of maintenance therapy (e.g. 240 mg Q2W). 
The Follow-up period includes a safety follow-up visit, response follow-up visits, and survival 
follow-up visits as described below. All patients should be followed for the intended duration of 
the study on an intent-to-treat basis for confirmation of PD and OS, regardless of the receipt of 
any new anticancer treatment. 
7.3.1 
Safety Follow-up Visit 
The safety follow-up visit should be conducted 30 to 37 days after the last dose of induction 
therapy. If anticancer treatments other than nivolumab are planned to start prior to 30 days after 
the last dose of induction therapy, the safety follow-up visit will be performed before the 
initiation of new anticancer treatment if possible.  
7.3.2 
Response Follow-up Visits  
Patients who complete the Induction period and/or who discontinue the Induction period for 
other reasons than confirmed PD will continue with response follow-up visits (after the 
completion of the safety follow-up visit) and should be assessed with imaging and assessments 
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The first response follow-up visit should occur 10 weeks post last dose of induction therapy. 
Subsequent response follow-up visits will be performed every 8 weeks for 32 weeks and then 
every 12 weeks thereafter. Every effort should be made to collect information regarding disease 
status until confirmed PD (iCPD) per iRECIST, until 70 PFS events are reached or until 18 
months post last patient randomized (whichever comes first). If required, images may be 
requested by BICR also after local iRECIST progression. 
Handling Progressive Disease During the Response Follow-up Period 
If, during the response Follow-up period a patient has iCPD confirmed by 2 scans, 4 to 8 weeks 
apart according to iRECIST criteria, the patient will continue with survival follow-up visits and 
will be contacted by phone (or, at the investigator’s discretion visit the hospital) every 12 weeks 
until the earliest of either 70 PFS events reached or 18 months post last patient randomized. 
From the PFS cut-off date is reached, survival follow-up visits will continue every 6 months for 
2 years.  
If PD is not confirmed according to iRECIST criteria, patient should continue with the response 
follow-up visits and imaging schedule according to Table 5 and Table 6.  
Handling Complete Response During the Response Follow-up Period 
If, during the response Follow-up period a patient has complete response (CR) according to 
RECIST 1.1, the patient will be treated according to the Investigator’s discretion. Patients who 
stop anticancer treatment while in CR will continue to undergo tumor imaging as scheduled in 
the study protocol. In the event of disease recurrence, any anticancer treatment including 
nivolumab may be resumed at the Investigator’s discretion. 
7.3.3 
Survival Follow-up Visits 
Patients who have confirmed iCPD according to iRECIST will continue with survival follow-up 
visits and be contacted per phone (or, at the investigator’s discretion visit the hospital) every 
12 weeks for survival status, assessment of SAEs and new anticancer treatments until the earliest 
of either 70 PFS events reached across both treatment arms or 18 months post last patient 
randomized.  
From the PFS cut-off date is reached, the survival follow-up visits will continue every 6 months 
for 2 years and only survival status will be collected. Detailed visit instructions will be provided 
by the sponsor at this time. 
The Sponsor may request survival status to be collected at additional timepoints during the study. 
For example, updated survival status may be requested prior to an IDMC review. 

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7.4 Withdrawal of Consent 
• A patient may withdraw consent from the study at any time at his/her own request. 
Although a patient is not obliged to give his/her reason(s) for withdrawing prematurely 
from a study, the Investigator should make a reasonable effort to ascertain the reason(s), 
while fully respecting the patient’s rights. 
• If the patient withdraws consent for disclosure of future information, the Sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
Survival status post withdrawal of consent can still be obtained from publicly available 
sources such as national cancer registries. 
• If a patient withdraws consent from the study, he/she may request destruction of any 
samples taken and not tested, and the Investigator must document this in the medical 
records. 
If Withdrawal of Consent Occurs During the Induction Period  
If possible, the procedures for the safety follow-up visit should be performed at the time of 
withdrawal. If the withdrawal takes place between 2 study visits, the patient should be asked to 
attend the safety follow-up visit as soon as possible. Any DTH registration card should be 
returned. The patient will no longer receive induction therapy or be followed at scheduled 
protocol visits.  
If Withdrawal of Consent Occurs During the Follow-up Period  
If possible, the procedures for the applicable visit where withdrawal takes place should be 
performed. If withdrawal takes place between 2 study visits, the patient should be asked to attend 
the next visit as soon as possible. Any DTH registration card should be returned. The patient will 
no longer be followed at scheduled protocol visits. 
7.5 Lost to Follow-up 
A patient will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. A patient is not considered lost to follow-up 
until the study is declared stopped. 
The following actions must be taken if a patient fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the patient and reschedule the missed visit as soon as 
possible and counsel the patient on the importance of maintaining the assigned visit 
schedule and ascertain whether the patient wishes to and/or should continue in the study 
or not. 

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• In cases in which the patient is deemed lost to follow-up, the Investigator or designee 
must make every effort to regain contact with the patient (where possible, 3 telephone 
calls and, if necessary, a certified letter to the patient’s last known mailing address or 
local equivalent methods). These contact attempts should be documented in the patient’s 
medical record. 
• For lost to follow-up patients, survival status can still be obtained from publicly available 
sources such as national cancer registries. 
7.6 End of Study 
The primary and secondary endpoint analysis will be conducted at the earliest of either 70 PFS 
events reached across both treatment arms or 18 months post last patient randomized. From the 
PFS cut-off date is reached, all patients will have survival follow-up visits every 6 months for 2 
years. The EOS is defined as the date of the last survival follow-up visit of the last patient 
undergoing the study.   

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8 Study Assessments and Procedures 
• Study procedures and their timing are summarized in the schedule of activities (Table 5 
and Table 6). Adherence to the study design requirements is essential and required for 
study conduct. 
• Protocol waivers or exemptions are not allowed with the exception of immediate safety 
concerns. These should be discussed with the Sponsor immediately upon occurrence or 
awareness to determine if the patient should continue or discontinue study treatment. 
• All screening evaluations must be completed and reviewed prior to randomization to 
confirm that potential patients meet all eligibility criteria. The Investigator will maintain a 
screening log to record details of all patients screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
• The maximum amount of blood collected from each patient over the duration of the 
study, including any extra assessments that may be required, is estimated to be 30 mL for 
local analysis and 95 mL for exploratory analysis. Patients who volunteer to take part in 
the extended exploratory sampling (Section 8.5) will have approximately 326 mL extra 
volume of blood collected. 
• Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples. 
8.1 Efficacy Assessments 
8.1.1 
Assessment of Tumor Response 
8.1.1.1 
Tumor Imaging 
Tumor imaging will be performed as detailed in the schedule of activities (Table 5 and Table 6) 
and should not be adjusted for dosing delays. It is important that patients are assessed according 
to the intended scanning schedule to prevent bias in analysis that may occur if one treatment arm 
is assessed differently compared to the other. If an unscheduled CT/MRI is performed during the 
study, subsequent protocol planned CTs/MRIs should be performed unless the time interval 
between the CTs/MRIs is <4 weeks.  
Mandatory tumor imaging consists of: 
• Contrast enhanced CT or MRI of chest, abdomen, and pelvis and all other known sites of 
disease. The CT scans are the preferred modality for measurable disease unless a patient 
has a severe iodine contrast allergy or other clinical condition that precludes optimal CT 
imaging, or the lesions are better visualized through the use of MRI. An MRI is the 
preferred modality for central nervous system (CNS) imaging in the case of suspected 
new CNS involvement. For a given patient, the same imaging modality should be used 
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• A CT or MRI of other body regions where lesions are present or suspected and can be 
visualized on CT or MRI (does not apply to superficial skin lesions). Once a lesion has 
been identified and documented with CT/MRI scanning, follow-up CT/MRI scans must 
be consistently repeated at all subsequent tumor assessment timepoints 
• Digital photography and documentation with label and ruler of all skin lesions  
All scheduled tumor images will be submitted for BICR. In addition, images that are obtained at 
an unscheduled timepoint and which relate to tumor assessment should also be submitted for 
BICR. Further details on tumor imaging and data transfer will be provided in a separate Imaging 
Guidance document. 
8.1.1.2 
Tumor Assessments 
Tumor assessments will be performed by the local Investigator/site and by BICR according to 
RECIST 1.1. In addition, the Investigator will evaluate new lesions and any potential PD by 
iRECIST (Appendix 4). For this protocol, target skin lesions are considered measurable only if 
measurable on CT or MRI. Measurable lesions that have previously been irradiated will not be 
considered target lesions unless size increase has been observed following completion of 
radiation treatment. 
As a clarification to RECIST 1.1, the following applies if a lesion is resected or receives any 
form of treatment or local therapy during the study: 
• The procedure itself, the pathology result (positive, negative, non-evaluable [NE]), and 
all post-procedure lesion assessments should always be recorded in the eCRF 
• Subsequent assessments for such patients will be NE until PD has been determined from 
the nadir 
Patients with PD per RECIST 1.1 and unconfirmed PD (iUPD) per iRECIST will have a new 
scan 4 to 8 weeks later to confirm PD per iRECIST (iCPD). A detailed description of response 
criteria is given in Appendix 4.  
If confirmatory scan performed 4 to 8 weeks after iUPD does not confirm progression, further 
scans continue as originally planned.  
Patient treatment will be determined by the Investigator. The BICR will perform assessments for 
statistical endpoint analysis only and will not interfere with Investigator assessments or treatment 
decisions. Treatment should continue until iCPD has been confirmed. 
8.2 Safety Plan and Assessments 
The administration of study treatment will be performed in a setting with emergency medical 
facilities and staff who are trained to monitor for and respond to medical emergencies. Eligibility 
criteria were selected to guard the safety of patients in this study. During the study, patients will 
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autoimmune conditions. Patients receiving UV1 injections will be observed in study site for 
4 hours following each treatment with UV1 and sargramostim. 
Planned timepoints for all safety assessments are provided in the schedule of activities. Adverse 
events will be reported throughout the study as described in Section 8.3. Any clinically 
significant abnormalities persisting at the PFS cut-off date reached will be followed by the 
Investigator until resolution or until a stable clinical status is reached but will not be recorded in 
the eCRF; however, clinically significant abnormalities should be noted in the patient’s medical 
file. 
8.2.1 
Independent Data Monitoring Committee 
During the course of the study, an IDMC will monitor safety information to ensure patient safety. 
The primary responsibility of the IDMC is to safeguard the interests of patients in the study. The 
IDMC will provide recommendations regarding stopping, modifying, or continuing the trial. The 
IDMC will consist of medical and statistical experts and provide their recommendations to the 
Sponsor. The safety and well-being of the study patients are the most important considerations. 
An organizational IDMC meeting will be held and an IDMC charter developed prior to the first 
patient screened in the study. The first operational IDMC meeting will take place approximately 
three weeks after the first 6 patients (3 in experimental and 3 in control arm) have completed the 
first treatment cycle (defined as until planned start of C2 dosing) of ipilimumab and nivolumab 
+/- UV1 and will include a safety review of all the included patients. The second IDMC meeting 
will take place approximately three weeks after the first 6 (3+3) patients have finished or 
discontinued the second cycle (defined as until planned start of C3 dosing), and the third meeting 
will take place approximately seven weeks after the 6 (3+3) patients have finished or 
discontinued planned cycle 4.  
The safety data of all included patients will be reviewed at each meeting. Subsequent meetings 
will be held every 3 months until the PFS cut-off date is reached or until last dose of induction 
therapy in the single arm UV1 cohort, whichever comes later. 
The IDMC’s assessment will be based on accumulated listings of the safety data collected in the 
study (ie, AEs, SAEs, hematology and chemistry data, withdrawals due to AEs, and treatment 
termination caused by AEs, etc). 
8.2.1.1 
Study Stopping Rules 
A decision to stop the study on the basis of safety findings will be done in accordance with the 
IDMC Charter for the study. Conditions that may warrant halting of the study include, but are not 
limited to the following: 
• The discovery of an unexpected, significant, or unacceptable risk to the patients 
• Subsequent discovery of a detrimental impact on efficacy of UV1 resulting in a negative 
risk/benefit balance 
• Cancellation of drug development  

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8.2.2 
Physical Examinations 
• Height will be measured at Screening only. 
• Weight should be measured using the same scale for a patient. 
• A physical examination of the skin, cardiac, pulmonary, abdomen, and peripheral lymph 
node status will be conducted. 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
• Clinically significant findings observed by the Investigator or symptoms reported 
spontaneously by the patient during the physical examination will be reported as AEs and 
in accordance with Section 8.3.3. 
8.2.3 
Vital Signs 
• Temperature, pulse rate and blood pressure will be assessed. 
• Blood pressure will be assessed in the seated position (after 5 minutes of rest) with a 
completely automated device. Manual techniques will be used only if an automated 
device is not available. 
8.2.4 
Eastern Cooperative Oncology Group 
The ECOG performance status will be measured as indicated in the schedule of activities. See 
Appendix 3 for the ECOG performance status scale. 
8.2.5 
Clinical Safety Laboratory Assessments 
Refer to Appendix 1 Clinical Laboratory Tests for the list of clinical laboratory tests to be 
performed and to the schedule of activities for the timing and frequency. 
The Investigator must review the laboratory report, document this review, and report any 
clinically relevant changes in the AE section of the eCRF. Abnormal laboratory findings should 
be reported as AEs if they are clinically significant (ie, medical intervention or corrective action, 
such as transfusions, initiation of antibiotics, other treatment regimens, or hydration, is required) 
or the abnormality is deemed clinically significant by the treating physician due to any other 
reason. The laboratory reports must be filed with the source documents. Laboratory values must 
be graded using National Cancer Institute Common Terminology Criteria for Adverse Events 
version 5.0. 
All abnormal laboratory tests with values considered clinically significant should be followed up 
per institutional practice. Every attempt should be made to perform repeat assessment until the 
values return to normal or baseline or if a new baseline is established, as determined by the 
Investigator.  

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8.2.6 
Toxicity of the Study Drugs 
There are no data on the toxicity of the combined therapy with all 4 study drugs in the present 
study. The combined toxicity of ipilimumab and nivolumab is known through several studies and 
is mentioned in the respective prescribing information. If a patient receiving ipilimumab and/or 
nivolumab develops suspected immune AEs, this must be handled according to the 
label/prescribing information for the relevant study drug(s). Further, both the IMPs and NIMPs 
may give general symptoms like fatigue. Please refer to the Investigator’s Brochure (IB)/label for 
the IMP/study drug for further information.  
8.3 Adverse Events 
8.3.1 
Definitions 
8.3.1.1 
Definition of AE 
An AE is any untoward medical occurrence in a subject or clinical study patient, temporally 
associated with the use of a study treatment, whether or not considered related to the medicinal 
product. 
Examples of events meeting the AE definition: 
• Any unfavorable laboratory test abnormality (hematology, clinical chemistry, or 
urinalysis) or other unfavorable safety assessment abnormality (eg, electrocardiogram, 
radiological scans, vital signs measurements), including those that worsen from Baseline, 
will be considered an AE. An unfavorable laboratory test abnormality may be one which 
requires medical intervention, requires action on the study drug(s) or is considered one at 
the discretion of the Investigator.  
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition 
• New conditions detected or diagnosed after study treatment administration even though it 
may have been present before the start of the study 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se should not be reported as an AE 
unless it is an intentional overdose taken with possible suicidal/self-harming intent. In 
that case, the overdose should be reported as an AE regardless of sequelae. 
• “Lack of efficacy” or “failure of expected pharmacological action” per se should not be 
reported as an AE. Such instances will be captured in the efficacy assessments. However, 
the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy should be 
reported as an AE if they fulfill the definition of an AE. 

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8.3.1.2 
Events Not Meeting the AE Definition 
The following are examples of events that do not meet the definition of an AE. These events 
should not be reported as AEs, unless there is evidence suggesting a causal relationship between 
the study treatment and the event: 
• The disease being studied. This includes signs, symptoms, clinically significant abnormal 
laboratory findings, or other abnormal safety assessments that are associated with the 
underlying disease, unless more severe than expected for the patient’s condition. 
• Progression from the disease being studied. This includes AEs definitely related to 
disease progression. 
• Death from the disease being studied. 
• Elective medical or surgical procedure (eg, endoscopy, appendectomy). Note: The 
condition that leads to the procedure is the AE (or part of medical history). 
• Situations in which an untoward medical occurrence did not occur, but the patient was 
hospitalized (social and/or convenience admission to a hospital). 
• Minor laboratory deviations outside of normal ranges and anticipated day-to-day 
fluctuations of pre-existing disease(s) or condition(s) present or detected at the start of the 
study that do not worsen. 
• Pregnancy, unless there is a suspicion that the study intervention may have interfered 
with the effectiveness of a contraceptive medication. All pregnancies must be reported in 
a pregnancy report form and should follow the procedures outlined in Section 8.3.4. 
• Elective abortions without complications. 
• Hospitalization for normal delivery of a healthy newborn. All pregnancy outcomes must 
be reported in a pregnancy outcomes form and should follow the procedures outlined in 
Section 8.3.4. 
8.3.1.3 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if seriousness 
conditions are met. 
An SAE is defined as any untoward medical occurrence that, at any dose: 
1. Results in death 
2. Is life-threatening 
The term ‘life-threatening’ in the definition of ‘serious’ refers to an event in which the patient 
was at risk of 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. 
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In general, hospitalization signifies that the patient has been detained (usually involving at 
least an overnight stay) at the hospital or emergency ward for observation and/or treatment 
that would not have been appropriate in the physician’s office or outpatient setting. 
Complications that occur during hospitalization are AEs. If a complication prolongs 
hospitalization or fulfills any other serious criteria, the event is serious. When in doubt as to 
whether ‘hospitalization’ occurred or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
Baseline is not considered an AE. 
4. Results in persistent disability/incapacity 
The term ‘disability’ means a substantial disruption of a person’s ability to conduct normal 
life functions. 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental 
trauma (eg, sprained ankle) which may interfere with or prevent everyday life functions but 
do not constitute a substantial disruption 
5. Is a congenital anomaly/birth defect 
6. Other situations 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the patient or may 
require medical or surgical intervention to prevent one of the other outcomes listed in the 
above definition. These events should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that 
do not result in hospitalization, or development of drug dependency or drug abuse. 
8.3.1.4 
Potential Drug Induced Liver Injury (DILI) 
All occurrences of potential DILIs, meeting the defined criteria, must be reported as SAEs. 
Potential drug induced liver injury is defined as: 
7. ALT or AST elevation > 3 times upper limit of normal (ULN), AND 
8. Total bilirubin > 2 times ULN, without initial findings of cholestasis (elevated alkaline 
phosphatase), AND 
9. No other immediately apparent possible causes of ALT or AST elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, pre-existing chronic or acute 
liver disease, or the administration of other drug(s) known to be hepatotoxic. 

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8.3.1.5 
Definition of Adverse Event of Special Interest 
Adverse events of special interest are events of scientific and medical interest specific to the 
further understanding of the safety of UV1 vaccination. An AESI may be serious or non-serious. 
For all AESIs, the Investigator should provide a description of the event, including but not 
limited to time of onset, treatment given, and outcome. Events falling under the AESI definition 
is an AESI regardless of the investigator’s assessment of relatedness to a study drug, and 
regardless of which treatment arm the patient is randomized to. 
Adverse events of special interest include any of the following events occurring on the same day 
of sargramostim, UV1, nivolumab or ipilimumab administration: 
• Anaphylactic shock 
• Anaphylactic reaction 
• Hypersensitivity (allergic reactions except local injection site reactions). 
8.3.1.6 
Definition of Suspected Unexpected Serious Adverse Reaction 
A suspected unexpected serious adverse reaction (SUSAR) is an SAE that is not expected, and 
for which there is a reasonable possibility that the study treatment caused the event. 
For UV1 and sargramostim, the reference safety information section in the UV1 IB is the 
reference document for what is considered to be expected SAEs. All clinical data in the IB are 
for use of the UV1 vaccination (ie, the combination of UV1 and sargramostim). An event that is 
expected for the UV1 vaccination is considered as expected for both UV1 and sargramostim. 
The causality assessment for SUSARs is the same as for other events, as described in 
Section 8.3.2.2. 
8.3.2 
Classification of Adverse Events 
8.3.2.1 
Severity and Grade 
The National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 
criteria will be used to grade AEs. 
The Investigator will assess severity for each AE and assign it to one of the following categories: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age 
appropriate instrumental Activities of Daily Living (ADL)*.  
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL**.  

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• Grade 4: Life-threatening consequences; urgent intervention indicated. 
• Grade 5: Death related to AE. 
Activities of Daily Living:  
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc.  
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
8.3.2.2 
Causality 
The Investigator is obligated to assess the causal relationship between each study treatment and 
an AE. The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
Causality must be reported as one of the following: 
1. Definitely: The AE is definitely related to the study treatment. 
2. Probably: There is high degree of certainty that the AE is related to the study treatment. 
3. Possibly: The AE could be related to either the study treatment or to concurrent 
disease/medication. 
4. Unlikely: There is high degree of certainty that the AE is NOT related to the study treatment. 
5. Not related: The AE is clearly due to other causes (eg, concurrent medication, underlying 
disease, etc.).  
If causality is assessed as definitely, probably, or possibly related, the event will be considered as 
related for regulatory reporting purposes.  
The Investigator will use clinical judgment to determine the relationship between an event and 
the study drugs. For an event to be assessed as related there should be a reasonable possibility 
that the drug caused the event. ‘Reasonable possibility’ means that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
Alternative causes, such as underlying disease(s), concomitant medication, and other risk factors, 
as well as the temporal relationship of the event to study treatment administration must be 
considered and investigated. 
The Investigator should also consult the IB and/or product information in their assessment. 
For each AE, the Investigator must document in the medical records or other source data that 
he/she has reviewed each AE and has provided an assessment of causality. 
There may be situations in which an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to the Sponsor. However, it is very important that the 
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before the initial transmission of the SAE data to the Sponsor. The Investigator may change 
his/her opinion of causality in light of follow-up information and send an SAE follow-up report 
with the updated causality assessment. 
8.3.3 
Adverse Event Reporting and Follow-up 
8.3.3.1 
Reporting 
Adverse events will be reported by the patient (or, when appropriate, by a caregiver, surrogate, or 
the patient’s legally authorized representative). Care will be taken not to introduce bias when 
detecting AEs. Open-ended and non-leading verbal questioning of the patient is the preferred 
method to inquire about AE occurrence (for example, “Have you experienced any new or 
changed symptoms since we last asked/since your last visit?”). 
From signing of the ICF until the first dose of induction therapy, only AEs/SAEs caused by 
study-specific procedures should be reported. All non-serious AEs should be reported from the 
first dose of induction therapy until 30 days after the last dose of induction therapy, or until new 
anticancer treatment is initiated (whichever comes first).  
All SAEs should be reported from the first dose of induction therapy until 70 PFS events are 
reached, until 18 months post last patient randomized or until new anticancer treatment is 
initiated (whichever comes first).  
The time periods for reporting of AEs and SAEs are outlined in Figure 4.  
Figure 4 
Time Periods for Reporting Adverse Events, Serious Adverse Events 
 
Signing of 
ICF 
1st dose 
induction 
therapy 
30 days post last dose 
induction therapy 
Earliest of 70 PFS events,  
18 month post last patient 
randomized 
or start of  
new anticancer treatment 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Only AEs/SAEs 
related to study 
procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All non-serious AEsa  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All SAEsb 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
a All non-serious AEs should be reported until 30 days after the last dose of induction therapy, or until new anticancer treatment is initiated 
(whichever comes first) 
b All SAEs should be reported until 70 PFS events are reached, until 18 months post last patient randomized or until new anticancer treatment 
is initiated (whichever comes first) 
 
When an AE occurs, it is the responsibility of the Investigator to review all documentation 
(eg, hospital progress notes, laboratory, and diagnostics reports) related to the event. 
The Investigator will then record all relevant AE information in the eCRF. 

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It is not acceptable for the Investigator to send photocopies of the patient’s medical records to 
the site monitor/Contract Research Organization (CRO)/Sponsor in lieu of completion of the AE 
eCRF page. 
There may be instances when copies of medical records for certain cases are requested by the site 
monitor/CRO/Sponsor. In this case, all patient identifiers, with the exception of the screening 
and/or randomization number, will be blinded on the copies of the medical records before 
submission. 
The Investigator should attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. In such cases, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE. 
Investigators are not obliged to actively inquire about AEs after the patient has been withdrawn 
from the study. However, if the Investigator learns of any SAE, including a death, at any time 
after a patient has been discharged from the study, and considers the event to be related to the 
induction therapy or study participation, the Investigator must promptly report to the Sponsor. 
Medical history will include all active conditions and any condition considered to be clinically 
significant by the Investigator. Medical history including demographic information (birth date, 
race, gender, etc.), current and historical medical conditions, cancer history (malignant 
melanoma, melanoma mutations, and other cancer types), and relevant surgical procedures must 
be collected at the Screening visit. Medical history will be recorded up until the first dose of 
induction therapy; however, AEs that occur between the time of signature of the ICF and the first 
dose of induction therapy that are believed to be at least possibly caused by study-specific 
procedures (ie, blood draws, imaging, biopsies, or other study procedures) will be reported as 
AEs as indicated. 
8.3.3.2 
Follow-up 
After the initial detection of an AE, the Investigator is required to proactively follow each patient 
at subsequent visits/contacts. Adverse events and SAEs that are ongoing beyond the required 
reporting timelines shall be followed up locally per institutional practice until resolution or 
stabilization or the patient is lost to follow up. 
The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the Sponsor to 
elucidate the nature and/or causality of the AE as fully as possible. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals. E.g. if an Adverse Event is classified as an AESI CTCAE grade ≥ 3, a 
plasma sample (from ≥ 5 mL whole blood) should be collected the same day as the event and 
stored for shipment to sponsor upon request.  
New or updated information will be reported in the eCRF until 70 PFS events are reached or 
until 18 months post last patient randomized (whichever comes first). 
 

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8.3.4 
Expedited Reporting  
Certain events require immediate reporting to allow the Sponsor to take appropriate measures to 
address potential new risks in a clinical study. The Investigator must report such events to the 
Sponsor immediately; under no circumstances should reporting take place more than 24 hours 
after the Investigator learns of the event. The following events must be reported by the 
Investigator to the Sponsor within 24 hours after learning of the event, regardless of relationship 
to study drug: 
• Serious AEs 
• Pregnancies 
If only limited information is initially available, follow-up reporting is required.  
The minimum information required for an initial report is: 
• Name of person sending the report (ie, name, address of Investigator) 
• Participant identification (screening/randomization number, initials, NOT participant 
name) 
• Protocol number 
• Description of SAE 
• Causality assessment; please refer to Section 8.3.2.2. 
However, as far as possible all information on the SAE form should be covered in the initial 
report. 
If an ongoing SAE changes in its intensity or relationship to study drug or if new information 
becomes available, follow-up SAE reporting should be sent to the Sponsor within 24 hours. 
8.3.5 
Regulatory Reporting Requirements for Investigator and Sponsor 
Prompt notification of SAEs (within 24 hours) by the Investigator to the Sponsor is essential so 
that legal obligations and ethical responsibilities towards the safety of patients and the safety of a 
study drug under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study drug under clinical investigation. The Sponsor 
will comply with country-specific regulatory requirements relating to safety reporting to the 
regulatory authority, Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), 
and Investigators. This includes annual safety updates.  
Suspected unexpected serious adverse reactions have additional reporting requirements. The 
Sponsor will report SUSARs as described below.  

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• If the SUSAR is fatal or life-threatening, regulatory authorities and IRBs/IECs will be 
notified within 7 calendar days after the Sponsor learns of the event. Additional follow-up 
(cause of death, autopsy report, and hospital report) information will be reported within 
an additional 8 days (15 days total). 
• If the SUSAR is not fatal or life-threatening but is otherwise serious, regulatory 
authorities and IRBs/IECs will be notified within 15 calendar days after the Sponsor 
learns of the event. 
The Sponsor will prepare Investigator safety reports for SUSARs according to local regulatory 
requirements and forward to Investigators as necessary. 
Only SUSARs related to the IMPs (UV1 and sargramostim) will be expeditiously reported by the 
Sponsor. 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (eg, summary or listing of SAE) from the Sponsor must file it along with the 
IB and notify the IRB/IEC, if appropriate according to local requirements. 
8.3.6 
Pregnancy 
Details of all pregnancies in female patients and female partners of male patients will be 
collected after the start of induction therapy and until 5 months after the last dose of UV1 
vaccination, nivolumab, or ipilimumab (whichever comes last). For male patients, this still 
applies if their partners become pregnant within 5 months after the last dose of UV1 vaccination, 
nivolumab, or ipilimumab (whichever is administered last.) The pregnancy and outcome of 
pregnancy should be monitored. 
The Sponsor has a responsibility to monitor the outcome of pregnancies where there has been 
maternal exposure to the study drug. 
All pregnancies must be reported by the Investigator to the Sponsor in a pregnancy report form 
within 24 hours after becoming aware of the pregnancy and should follow the procedures 
outlined in Section 8.3.4. The Investigator must follow-up and document the course and outcome 
of all pregnancies even if the patient was discontinued from the study or if the study has ended. 
All pregnancy outcomes must be reported by the Investigator to the Sponsor in a pregnancy 
outcome report form within 30 days after he or she has gained knowledge of the outcome. 
Elective abortions without complications should not be handled as AEs. The outcome of all 
pregnancies (spontaneous miscarriage, elective termination, normal birth, or congenital 
abnormality) must be followed up and documented even if the patient was discontinued from the 
study. 
Pregnancy alone is not regarded as an AE unless there is a suspicion that the study intervention 
may have interfered with the effectiveness of a contraceptive medication. 
Any pregnancy complication should be reported as an AE. Hospitalization for normal delivery of 
a healthy newborn should not be considered an SAE. 

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Any SAE that occurs during pregnancy and abnormal pregnancy outcomes (eg, maternal serious 
complications, spontaneous or therapeutic abortion, ectopic pregnancy, stillbirth, neonatal death, 
congenital anomaly, or birth defect) should be reported even if they occur outside the normal 
SAE reporting period. These events must be reported within 24 hours in accordance with the 
procedure for reporting SAEs. 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with one of the following: 
• Documented hysterectomy 
• Documented bilateral salpingectomy 
• Documented bilateral oophorectomy 
NOTE: Documentation can come from the site personnel’s review of the patient’s medical 
records, medical examination, or medical history interview. 
Post-menopausal female 
• A post-menopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the post-menopausal 
range may be used to confirm a post-menopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient. 
• Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of post-menopausal status before study randomization. 
8.4 Exploratory Assessments 
Blood samples for exploratory analysis of immune-related gene profiling and immune- and 
tumor-related protein and gene profiles will be collected from all patients. In the experimental 
arm, collection will be done on Days 1, 31, and 52; and in the control arm on Days 1, 43, and 64. 
Collection will also be done in both treatment arms on the safety follow-up visit and 18 weeks 
post last dose of induction therapy (2nd response follow-up visit). Assessments related to these 
samples are described in Table 8. 

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8.4.1 
Biomarkers 
Blood samples for DNA and RNA isolation will be collected from all patients. Analysis of DNA 
and RNA isolated from blood will include, but is not limited to, analysis of the T cell receptor 
repertoire, analysis of circulating tumor DNA, and analysis of microRNAs. Blood samples may 
be also used to isolate and analyze circulating tumor cells.  
Blood samples will be stored, and analysis may be performed on biomarker variants thought to 
underlie the interplay between immune activation provoked by vaccination with UV1 and 
inhibition of tumor resistance mechanisms and peripheral immune tolerance induced by 
checkpoint blockade. Analyses may include but are not limited to levels of antibodies specific for 
vaccine peptides, tumor-specific antigens, cytokines, chemokines, and inflammatory factors. 
Assessments of potential biomarkers may be used to evaluate their association with observed 
clinical responses to UV1 vaccination in combination with nivolumab and ipilimumab, or 
nivolumab and ipilimumab alone. 
The final disposition of samples will be conducted per local regulations. 
Samples may be stored for a maximum of 5 years (or according to local regulations) following 
the last patient’s last visit for the study at a facility selected by the Sponsor to enable further 
analysis of biomarker responses. 
8.5 Extended Exploratory Cohort 
A cohort of approximately 40 patients at selected sites will be asked to volunteer for additional 
biological sampling and analysis. Extended blood sampling, tumor biopsy collection, fecal 
sampling, and DTH testing (only for experimental arm) will be conducted on patients in the 
Extended Exploratory Cohort. Exploratory assessments related to the biological samples 
collected from this cohort of patients with rationale and objectives are described in Appendix 2. 
The samples collected in the Extended Exploratory Cohort will be in addition to those required 
elsewhere per protocol for all patients. 
8.6 Single Arm UV1 Cohort 
To support the Extended Exploratory Cohort of the study, an additional 20 patients at selected 
sites will be enrolled in a single arm UV1 cohort for collection of additional biological material.  
(Appendix 7). 
 

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9 Statistical Methods 
The statistical considerations summarized in this section outline the plan for data analysis of this 
study. Any deviations from the planned analyses will be described in the Statistical Analysis Plan 
and justified in the final integrated study report. 
9.1 Statistical Hypothesis 
The primary endpoint is PFS. Under the null hypothesis, the PFS HR for UV1 vaccination in 
combination with nivolumab and ipilimumab versus nivolumab and ipilimumab is assumed to be 
unity. Under the alternative hypothesis, the PFS HR is assumed to be 0.60 or better, representing 
a beneficial effect on PFS for UV1 vaccination in combination with nivolumab and ipilimumab 
compared to nivolumab and ipilimumab. 
9.2 Sample Size Determination 
To test the PFS null hypothesis with 80% power and a 1-sided alpha level of 0.10, a total of 
70 PFS events are required. Hodi et al (2018) 14 provides data on PFS with nivolumab and 
ipilimumab in patients with advanced melanoma. Assuming a similar shape of the PFS curve for 
nivolumab and ipilimumab is observed in the current study, 154 patients randomized over a 
15-month period and followed thereafter for a minimum of 12 months will give a mean 
follow-up of PFS events of approximately 20 months. Follow-up for survival will continue for an 
additional 24 months after the PFS analysis at which time 60 deaths are expected to have 
accrued; this many deaths, an observed OS HR of 0.60 would reach p<0.025 1-sided. 
As of 19 September 2023, blinded event accrual stood at 63 PFS events. A blinded examination 
of the overall PFS Kaplan Meier curve made as of 23 July 2023, and then repeated as of 19 
September 2023, showed strong evidence for a plateau at 54 to 55% of subjects alive and without 
progression. Such a PFS curve plateau is not uncommon for IO therapies. In CheckMate 67, 
nivolumab plus ipilimumab, nivolumab alone and ipilimumab alone were evaluated in advanced 
melanoma (Hodi 2018). This study formed the basis of the sample size calculations for the 
current study and showed a prolonged PFS tail for nivolumab plus ipilimumab plateauing at 
approximately 40% for subjects alive and without progression. However, the blinded data 
realized thus far has shown a higher plateau at 54 to 55% for subjects alive and without 
progression. 
Specifically, there seems to be very little contribution to PFS events after 18 months in the study, 
with the PFS curve nearing asymptote. The plateau in the current study commences at 
approximately 21 months post first subject randomized with an estimated 56.02% of subjects 
alive and without progression and persists thereafter for 15 months, out to 36 months at which 
time 54.32% subjects are alive and without progression, i.e. an increase in the progression rate of 
only 1.7% over 15 months. Based on the projected PFS curve, 70 PFS events are not expected to 
be reached by late 2028 at which time 69.3 events, 90% CI of (69.2, 72.3), are expected.   
Given the observed plateau in the accrual of PFS events, it has been decided to execute the 
primary analysis of PFS at the earliest of either 70 PFS events reached across both treatment 

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arms or 18 months post last patient randomized. An analysis with slightly fewer PFS events has 
negligible impact on the observed HR to reach a given level of statistical significance. 
9.3 Analysis Populations 
For purposes of analysis, the following analysis populations are defined: 
Analysis populations 
Description 
Intention-to-treat (ITT) 
population  
All randomized patients. Efficacy data in this population will be 
summarized by randomized treatment. The primary PFS and secondary 
OS analysis will be assessed in the ITT population. Patients will be 
analyzed by the treatment arm to which they are randomized. 
Response evaluable 
population 
All randomized patients with measurable disease by RECIST 1.1. The 
secondary endpoint analyses of ORR and DOR will be assessed using 
the response evaluable population. Patients will be analyzed by the 
treatment arm to which they are randomized. 
Safety population 
All randomized patients who receive at least one dose (or partial dose) 
of induction therapy. Patients will be assessed by the treatment 
received, based on the first dose of study drug. 
9.4 Statistical Analysis 
9.4.1 
General Considerations 
Demographic data and disease-related baseline characteristics will be summarized using 
descriptive statistics (count and percent, mean, median, standard deviation, minimum, and 
maximum). All patient, efficacy, and safety data will be summarized. In addition to the 
summarized analysis plan outlined below, a Statistical Analysis Plan (SAP) will be written and 
finalized prior to the first planned data analysis. The SAP will provide a detailed and expanded 
description of the statistical methods outlined in this protocol. Additional analyses, such as in 
important subgroups, will also be described in the SAP. 
9.4.2 
Efficacy Analyses 
9.4.2.1 
Primary Efficacy Analyses 
Progression Free Survival  
Progression free survival is defined as time from randomization to progression (by BICR) or 
death from any cause, whichever occurs first. A Cox proportional hazards regression model will 
be used to analyze PFS on an ITT basis. Patients who have not progressed or died will be 
censored at their last follow-up tumor assessment. The model will include a single covariate for 
randomized treatment and covariates for baseline ECOG (0 versus 1) score. The HR will be 
estimated from the model along with the associated 2-sided CI and 2-sided p-value. The data will 
also be displayed using Kaplan-Meier curves and median PFS times will be estimated. The PFS 

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at 12 months will be estimated from the Kaplan-Meier curves along with the associated 80% and 
95% Cis. 
Sensitivity Analyses of the Progression Free Survival 
Several sensitivity analyses will be performed on the primary endpoint: 
i. 
As per FDA guidance, a sensitivity analysis will be performed in patients who started any 
subsequent anticancer treatment without a prior reported progression. Patients will be 
censored at the last evaluable tumor assessment prior to initiation of the subsequent 
anticancer treatment; and 
ii. 
A log rank test on PFS as determined by BICR. The 2-sided p-value will be extracted and 
presented alongside the results of the Cox analysis; and  
iii. 
A Cox regression analysis on PFS as determined by the local Investigator’s review; and 
iv. 
A log rank test on PFS as determined by the local Investigator’s review. The 2-sided 
p-value will be extracted and presented alongside the results of the Cox analysis. 
Additional sensitivity analyses may be specified in the SAP. 
9.4.2.2 
Secondary Efficacy Analyses 
Overall Survival 
Overall survival is defined as the time from randomization to death from any cause. Overall 
survival will be analyzed in a fashion similar to that described for PFS. Overall survival data at 
the time of the PFS analysis and with an additional follow-up thereafter will be analyzed until 
defined end of study to provide evidence supportive of PFS. 
Objective Response Rate 
Objective response rate is defined as the proportion of patients with a best response of CR or PR 
(by BICR). The ORR will be analyzed by exact logistic regression. The model will include a 
single covariate for randomized treatment and covariates for baseline ECOG (0 versus 1) score. 
The exact odds ratio will be estimated from the model along with the associated 80% and 95% 
Cis and 2-sided p-value. Exact Clopper-Pearson 2-sided 80% and 95% confidence limits will be 
calculated for the proportion of patients with ORR in each arm. 
Duration of Response 
Duration of response is defined as the time from first CR or PR (by BICR), whichever is 
recorded first, to progression (by BICR) or death from any cause, whichever occurs first. The 
DOR will be analyzed via Cox regression modelling with a fixed effect term for randomized 
treatment. The HR will be estimated from the model along with the associated 80% and 95% CI 
and 2-sided p-value. The data will also be displayed using Kaplan-Meier curves; median DOR 
and the 80% and 95% Cis will be estimated from the Kaplan-Meier curve by treatment arm. 
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based on the expected duration of response as per Ellis et al (2008)32 as this analysis includes all 
randomized patients, including those who did not respond.  
9.4.3 
Safety Analyses 
Adverse events will be classified using the latest version of the Medical Dictionary for 
Regulatory Activities (MedDRA) classification system. Treatment-emergent AEs (TEAEs) will 
be summarized. A TEAE is defined as an AE that was not present prior to first study treatment 
but appeared following treatment, or was present at treatment initiation but worsened during 
treatment. An AE that was present at treatment initiation but resolved and then reappeared while 
the patient was on treatment is a TEAE (regardless of the intensity of the AE when the treatment 
was initiated). For simplicity, TEAEs will be referred to as AEs in this protocol. Adverse events 
will be summarized descriptively by treatment arm, in terms of body system and MedDRA 
preferred term. Patients with multiple occurrences of the same AE will only be counted once at 
the maximum severity/grade for each preferred term, system organ class, and overall. Adverse 
events will be summarized in terms of the number and percentages of patients experiencing 
related AEs, SAEs, AEs leading to dose interruption, AEs leading to withdrawal from 
randomized treatment, and AEs leading to death. In the event that a patient experiences repeated 
episodes of the same AE, the patient will be counted once within each system organ class and 
similarly counted once within each preferred term and the event with the highest severity grade 
and/or strongest causal relationship to each treatment will be used for incidence tabulations.  
Laboratory values and change from Baseline will be summarized using descriptive statistics at 
scheduled visits by treatment. Shift tables of the worst on-study laboratory toxicity relative to 
Baseline will be presented by treatment arm. Patient listings of Grades ≥3 laboratory toxicities 
will be provided. 
Vital signs and ECOG performance status (observed and change from Baseline) will be 
summarized using descriptive statistics by timepoint and treatment. 
9.4.4 
Exploratory Analyses 
Biomarkers and parameters for immunological mode of action (eg, T-cell response) will be 
summarized per timepoint with descriptive statistics. The potential relationship between 
exploratory biomarkers and treatment response/immune response will be summarized using 
cross-tabulation (biomarker measured as present Yes/No) and level of biomarker (mean, standard 
deviation, median, minimum, and maximum) for each response group (biomarkers measured on 
continuous scales). 
9.5 Timing of the Analyses 
This study is event driven so that the timing of the primary endpoint analysis is dependent upon 
the attainment of 70 PFS events and is not calendar based. Based on the assumptions supporting 
the sample size calculation (Hodi, 2018), it is expected that 70 PFS events will have accrued at 
around 27 months after the first patient is randomized. 

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However, as of 19 September 2023, blinded event accrual stood at 63 PFS events. A blinded 
examination of the overall PFS Kaplan Meier curve made as of 23 July 2023, and then repeated 
as of 19 September 2023, showed strong evidence for a plateau at 54-55% of subjects alive and 
without progression. Given the observed plateau in the accrual of PFS events, it has been decided 
to execute the primary analysis of PFS at the earliest of either 70 PFS events reached across both 
treatment arms or 18 months post last patient randomized. Follow-up for survival will continue 
for an additional 24 months after the PFS cut-off date, at which time 60 deaths are expected to 
have accrued. 
The secondary endpoints will also be analyzed at the earliest of either 70 PFS events reached 
across both treatment arms or 18 months post last patient randomized. 
In addition, overall survival will be analyzed until defined end of study.  
 
 
 

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10 Regulatory, Ethical, and Study Oversight Considerations 
10.1 Regulatory and Ethical Considerations 
• This study will be conducted in accordance with Good Clinical Practice (GCP) as defined 
by the International Conference of Harmonisation (ICH), ethical principles derived from 
the Declaration of Helsinki, the General Data Protection Regulation, the United States 
Code of Federal Regulations (CFR) Title 21, European regulation No 536/2014, and other 
applicable laws and regulations. 
• The study will be conducted in compliance with the protocol and amendments, as 
applicable. 
• The protocol, protocol amendments, ICF, and other relevant documents (eg, 
advertisements) will receive required regulatory authority approval and IRB/IEC 
approval/favorable opinion before the study is initiated. 
• Any substantial amendments to the protocol will require regulatory authority approval 
and IEC/IRB approval/favorable opinion before implementation of changes made to the 
study design, except for changes necessary to eliminate an immediate hazard to study 
patients. 
• The Investigator will ensure that: 
o Written and dated approval/favorable opinion from the IRB/IEC for the protocol, 
ICF, and other relevant documents have been obtained before study initiation 
o The IRB/IEC has been provided with a copy of the IB 
o Written summaries of the status of the study are provided to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
o The IRB/IEC is notified of SAEs and other significant safety findings as required 
by IRB/IEC procedures 
o Overall conduct of the study at the site and adherence to national and international 
regulations, IRB/IEC requirements, and all other applicable local regulations are 
followed. 
10.2 Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information in accordance with local regulations to allow the Sponsor to submit complete and 
accurate financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study. 

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10.3 Informed Consent Process 
• The Investigator or his/her representative will explain the nature of the study to the 
patient or his/her legally authorized representative and answer all questions regarding the 
study. 
• Patients must be informed that their participation is voluntary. Patients or their legally 
authorized representative will be required to sign a statement of informed consent that 
meets the requirements of 21 CFR 50, local regulations, ICH guidelines, Health 
Insurance Portability and Accountability Act requirements, the European Union General 
Data Protection Regulation, IRB/IEC requirements, and applicable laws regulations. 
• The medical record must include a statement that written informed consent was obtained 
before the patient was randomized in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
• Patients must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
• A copy of the ICF(s) must be provided to the patient or the patient’s legally authorized 
representative. 
• Prior to any study-specific procedures being performed, all patients must sign the ICF. 
Patients that decide to take part in the extended exploratory analyses need to sign a 
separate ICF (Appendix 2).  
• After the patient has signed the ICF, the site will enter information into the IWRS, or 
equivalent, which will assign a unique screening number. Once assigned, a screening 
number cannot be re-used for any reason.  
Patients who are rescreened are required to sign a new ICF and will receive a new screening 
number. 
If a protocol amendment is required, the ICF may need to be revised to reflect the changes to the 
protocol. If the ICF is revised, it must be reviewed and approved by the appropriate IEC/IRB and 
signed by all patients subsequently screened in the study as well as those currently randomized in 
the study. 
10.4 Data Protection 
• Participants will be assigned a unique identifier by interactive web response system. Any 
patient records or datasets that are transferred to the Sponsor will contain the identifier 
only; patient names or any information which would make the patient identifiable will 
not be transferred. 
• The patient must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with relevant data protection laws. The level of disclosure must 
also be explained to the patient. 

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• The patient must be informed that his/her medical records may be examined by study 
monitors, quality assurance auditors, and other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
10.5 Dissemination of Clinical Study Data 
When the Clinical Study Report is completed, the Sponsor will provide the major findings of the 
study to the Investigator. A summary of the study results will also be posted in a publicly 
accessible database (eg, www.ClinTrials.gov). The results may also be submitted for publication. 
10.6 Data Quality Assurance 
• All patient data relating to the study will be recorded in an eCRF unless transmitted to the 
Sponsor or designee electronically (eg, laboratory data). The Investigator is responsible 
for verifying that data entries are accurate and correct by electronically signing the eCRF. 
• The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
• The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
• The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
• Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of patients are being protected; and that the 
study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements. 
• Once the eCRF clinical data have been submitted to the central server at the independent 
data center, corrections to the data fields will be captured in an audit trail. The reason for 
change and the name of the person who performed the change, together with the time and 
date, will be logged to provide an audit trail. 
• If additional corrections are needed, the responsible monitor or data manager will raise a 
query in the eCRF. The appropriate staff at the study site will answer queries sent to the 
Investigator. The name of the staff member responding to the query, and time and date 
stamp will be captured to provide an audit trail.  
• The specific procedures to be used for data entry and query resolution using the eCRF 
will be provided to study sites in a training manual. In addition, site personnel will 
receive training on the eCRF. 
10.7 Source Documents 
• Source documents provide evidence for the existence of the patient and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s site. 

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• Data reported in the eCRF that are transcribed from source documents must be consistent 
with the source documents, or the discrepancies must be explained. The Investigator may 
need to request previous medical records or transfer records, depending on the study. 
Also, current medical records must be available. 
The study site will maintain an Investigator site file containing, at a minimum, the IB, protocol 
and any amendments, drug accountability records, correspondence with the IEC/IRB, the 
identification of all participating patients, study-specific source documents, source worksheets, 
all original signed and dated ICF forms, and detailed records of drug disposition to enable 
evaluations or audits from regulatory authorities and the Sponsor or its designees. 
The Investigator will retain the Investigator site file to be maintained until at least 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 at least 2 years have elapsed since the 
formal discontinuation of clinical development of the investigational product.  
No data should be destroyed without the agreement of the Sponsor. Should the Investigator wish 
to assign the study records to another party or move them to another location, the Sponsor must 
be notified in writing of the new responsible person and/or the new location.  
Patients’ medical records and other original data will be archived in accordance with the 
archiving regulations or facilities of the investigational site. 
10.8 Study and Site Closure 
For reasonable cause, the Sponsor may terminate a study site or the entire study prematurely. 
When feasible, a 30-day written notification will be given. Conditions that may warrant 
termination include, but are not limited to: 
• The discovery of an unexpected, significant, or unacceptable risk to the patients 
• Difficulties in the screening and/or randomization of patients – individual sites or entire 
study may be closed/terminated based on this criterion 
• Insufficient adherence to protocol requirements (non-compliance) – individual sites may 
be closed based on this criterion 
• Cancellation of drug development. 
Should this be necessary, the Sponsor will arrange discontinuation procedures. In terminating the 
study, the Sponsor will ensure that adequate consideration is given to the protection of the 
patients’ interests. 
Regardless of the reason for termination, all data available for the patient at the time of 
discontinuation of follow-up must be recorded in the eCRF. In terminating the study, the 
Investigator will ensure that adequate consideration is given to the protection of the patients’ 
interests. 

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10.9 Publication Policy 
• The results of this study may be published and/or presented at scientific meetings. If this 
is foreseen, the Investigator agrees to submit manuscripts or abstracts to the Sponsor 
before submission. This allows the Sponsor to protect proprietary information and to 
provide comments. 
• The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter studies only in their entirety and not as individual site 
data. In this case, a coordinating Investigator will be designated by mutual agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
• All data generated from this study are the property of the Sponsor and will be held in 
strict confidence along with all information furnished by the Sponsor. Independent 
analysis and/or publication of these data by the Investigator(s) or any member of their 
staff is not permitted without the prior, written consent of the Sponsor. Written 
permission to the Investigator will be contingent on the review by the Sponsor of the 
manuscript and will provide for nondisclosure of Sponsor confidential or proprietary 
information. In all cases, the parties agree to submit all manuscripts or abstracts to all 
other parties 30 days prior to submission. This will enable all parties to protect 
proprietary information and to provide comments based on information that may not yet 
be available to other parties. 
10.10 Protocol Approval and Amendment 
Before the start of the study, the study protocol and/or other relevant documents will be reviewed 
and/or approved by the IRB/IEC, and of regulatory authorities in accordance with local legal 
requirements. The Sponsor must ensure that all ethical and legal requirements have been met 
before the first patient performs any study-specific procedures. 
This protocol is to be followed exactly. To alter the protocol, amendments must be written, 
receive approval from the appropriate personnel, and receive IRB/IEC/regulatory authority 
approval prior to implementation (if appropriate). In the United States: The protocol 
amendment(s) will be submitted to the Investigational New Drug under which the study is being 
conducted. 
Administrative changes may be made without the need for a formal amendment. All amendments 
will be distributed to all protocol recipients, with appropriate instructions. 
10.11 Liability and Insurance 
The Sponsor will take out reasonable third-party liability insurance cover in accordance with all 
local legal requirements. The civil liability of the Investigator, the persons instructed by him or 
her, and the study site, practice, or institute in which they are employed and the liability of the 

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Sponsor with respect to financial loss due to personal injury and other damage that may arise as a 
result of the carrying out of this study are governed by the applicable law. 
The Sponsor will arrange for patients participating in this study to be insured against financial 
loss due to personal injury caused by the pharmaceutical products being tested or by medical 
steps taken in the course of the study. 
10.12 Access to Source Data 
On behalf of the Sponsor, a study monitor will contact and visit the Investigator at the study 
center prior to entry of the first patient and at appropriate intervals during the study until after the 
last patient is completed. The monitor will also perform a study closure visit. 
In accordance with ICH GCP guidelines, the Investigator must ensure provision of sufficient 
time, reasonable space, and adequate qualified personnel for the monitoring visits. The visits are 
for the purpose of verifying adherence to the study protocol and the completeness, consistency, 
and accuracy of data entered on the eCRF and other documents.  
The Investigator will make all source data (ie, the various study records, the eCRFs, laboratory 
test reports, other patient records, drug accountability forms, and other pertinent data) available 
for the monitor and allow access to them throughout the entire study period. Monitoring is done 
by comparing the relevant site records of the patients with the entries on the eCRF (ie, source 
data verification). It is the monitor’s responsibility to verify the adherence to the study protocol 
and the completeness, consistency, and accuracy of the data recorded on the eCRFs. 
By agreeing to participate in the study, the Investigator agrees to cooperate with the monitor and 
to ensure that any problems detected in the course of the monitoring visits are resolved. 
Representatives from the Sponsor may also contact and visit the Investigators and monitor data 
during the study. 
 
 

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Appendix 1 Clinical Laboratory Tests 
• Local laboratory analysis (all patients) are detailed in Table 7. 
• Central laboratory sampling for exploratory analysis (all patients) are detailed in Table 8.  
• Extended Exploratory Cohort assessments (approximately 40 patients) are detailed in 
Appendix 2, Table 9, and Table 10. 
• Additional tests may be performed at any time during the study as determined necessary 
by the Investigator or required by local regulations. 
• Blood samples must be collected prior to administration of treatment. 
Table 7 
Local Laboratory Analysis (all patients, N=154) 
Laboratory 
Assessments 
Parameters 
Hematology 
 
Red blood cell (RBC) Count 
Hemoglobin 
Hematocrit 
White blood cell (WBC) Count 
Platelet Count 
Absolute neutrophil count 
RBC Indices: 
Mean corpuscular 
volume 
Mean corpuscular 
hemoglobin 
WBC count with Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Clinical 
Chemistry from 
serum or plasma1 
 
Blood urea nitrogen 
(BUN)/Urea*  
Potassium 
Total and direct bilirubin 
Creatinine 
Sodium 
Albumin 
Chloride 
Glucose (non-fasting) 
Calcium 
Alkaline phosphatase 
Aspartate aminotransferase (AST/GOT) 
Alanine aminotransferase (ALT/GPT) 
Lactate dehydrogenase 
Uric acid 
Thyroid panel (TSH and fT4) 
Other Screening 
Tests 
• Hepatitis B surface antigen and hepatitis C virus antibody 
• Human chorionic gonadotropin pregnancy test (for women of childbearing potential)2 
NOTES: 
1 All events of ALT or AST 3 × upper limit of normal (ULN) AND bilirubin 2 × ULN, which may indicate severe liver injury 
(possible Hy’s Law), must be reported as a serious adverse event. 
2 Local urine testing will be standard for the protocol unless serum or plasma testing is required by local regulation or Institutional 
Review Board/Independent Ethics Committee. If the urine test is positive or cannot be confirmed as negative, a serum or plasma 
pregnancy test will be required. 
*Assessment of urea to be performed by sites where laboratories are not using BUN. 
Total amount of blood for local analysis will be approximately 30 mL per patient.  
Investigators must document their review of each laboratory safety report. 

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Table 8 
Central Laboratory Sampling for Exploratory Analyses (all patients, N=154) 
Treatment arm 
Visits 
Laboratory assessments 
Volume of blood 
collected  
Experimental arm 
• Day 1  
• Day 31 
• Day 52 
• Safety Follow-up  
• 18 weeks post last 
dose of induction 
therapy (2nd response 
follow-up visit) 
• Blood for immune-related gene profiling 
based on cell-free plasma DNA and 
cellular genomic DNA 
• Blood for generation of plasma 
95 mL blood over 
5 visits 
Control arm 
• Day 1 
• Day 43  
• Day 64 
• Safety Follow-up  
• 18 weeks post last 
dose of induction 
therapy (2nd response 
follow-up visit) 
• Blood for immune-related gene profiling 
based on cell-free plasma DNA and 
cellular genomic DNA 
• Blood for generation of plasma 
95 mL blood over 
5 visits 
 
Total blood volume 
 
95 mL blood / 
patient 
 
 
 

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Appendix 2 Extended Exploratory Cohort (N= approximately 40 patients) 
Background 
As part of the development and evaluation of the UV1 vaccine, a cohort of approximately 
40 patients at selected sites will be asked to volunteer for additional biological sampling and 
analysis. The patients will have to sign a separate Informed Consent Form (ICF) to enroll in this 
part of the study. The analysis of the samples will aim to reveal how changes in biological 
markers, including tumor mutational burden (TMB), and T-cell receptor (TCR) repertoire 
diversity reflect the efficacy of the treatments. The goal is to further elucidate and characterize 
the immunological mechanisms induced with UV1 in combination with nivolumab and 
ipilimumab in blood and tumor. 
Research Objectives and Assessments 
A biobank will be established for current and future analysis of the samples collected. The 
specific research objectives include, but are not restricted to investigate if: 
• UV1 vaccination in addition to ipilimumab and nivolumab: induce a broader repertoire of 
TCR specificities including epitopes not included in the UV1 vaccine compared to 
ipilimumab and nivolumab.  
• UV1 vaccination in addition to ipilimumab and nivolumab: induces changes in the 
post-treatment TMB from the pre-treatment TMB compared to ipilimumab and 
nivolumab.  
• UV1 vaccination in addition to ipilimumab and nivolumab: induces changes in the 
post-treatment immune cell infiltrate of the tumor from the pre-treatment immune cell 
infiltrate compared to ipilimumab and nivolumab. 
• UV1 vaccination in addition to ipilimumab and nivolumab: induces vaccine-specific 
immune responses in blood.  
• The microbial composition in feces pre-treatment affects response to treatment with UV1 
vaccination in addition to ipilimumab and nivolumab compared to ipilimumab and 
nivolumab. 
• UV1 vaccination in addition to ipilimumab and nivolumab: induces delayed-type 
hypersensitivity (DTH) responses.  
Exploratory Endpoints 
• Correlation in the change in TCR repertoire in blood over time to clinical response in 
both treatment arms. 
• Correlation between vaccine-specific immune response in blood and clinical response in 
the UV1 in addition to ipilimumab and nivolumab arm.  
• Correlation between DTH and clinical response in the UV1 in addition to ipilimumab and 
nivolumab arm. 

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• Change in the post-treatment TMB from pre-treatment TMB in both treatment arms.  
• Change in composition of the immune cell infiltrate of the tumor post-treatment 
compared to pre-treatment in both treatment arms.  
• Correlation of microbiologic composition of fecal samples to response to treatment in 
both treatment arms. 
Target Population 
Selected study sites that have the necessary laboratory facilities to collect and handle the 
requested lab samples can take part in the extended laboratory cohort part of the study. Patients 
eligible for the study will be offered to take part in the Extended Exploratory Cohort until the 
needed number of patients in the cohort is reached.  
Discontinuation from Extended Exploratory Cohort 
Patients can withdraw their extended exploratory cohort consent at any time without this 
affecting their care and treatment. These patients can continue in the main part of the study. In 
case of withdrawal of extended exploratory cohort consent, the patient can request all samples 
collected under this consent to be destroyed. Results from samples already analyzed will not be 
deleted. 
Sample Collection and Assessments 
The sample collection and assessments in the Extended Exploratory Cohort will be done in 
addition to those requested elsewhere per protocol. In the experimental arm these will be done 
during the Screening period, and at Days 1, 31, and 52. In the control arm these will be done 
during the Screening period, and at Days 1 and 43. In both treatment arms sample collection and 
assessment will also be done at the safety follow-up visit and 18 weeks post last dose of 
induction therapy. Sample type and assessments are described in Table 9 and Table 10 below. 

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Table 9 
Extended Exploratory Cohort Assessments – Experimental Arm 
Visit 
Assessment 
Volume of tissue collected  
Screening 
Fecal sample 
Tumor biopsy (FFPE biopsy) 
Tumor biopsy (Snap-frozen biopsy) 
Dedicated sample card 
At the pathologist’s decision (one biopsy) 
At the pathologist’s decision (two snap-frozen) 
Day 1 
Whole blood for DNA 
SNP sample 
Whole blood for PBMC 
DTHa 
3 mL blood 
3 mL blood 
80 mL blood 
Not applicable 
Day 31  
Whole blood for PBMC 
DTHa 
80 mL blood 
Not applicable 
Day 52  
DTHa 
Not applicable 
Safety follow-up 
Whole blood for PBMC 
Tumor biopsy (FFPE biopsy) 
Tumor biopsy (Snap-frozen biopsy) 
DTHa 
80 mL blood 
At the pathologist’s decision (one biopsy) 
At the pathologist’s decision (two snap-frozen) 
Not applicable 
18 weeks post last dose 
of induction therapy 
(2nd response follow-up 
visit) 
Whole blood for PBMC 
DTHa 
80 mL blood  
Not applicable 
Total blood volume 
 
326 mL blood / patient 
Abbreviations: DNA = deoxyribonucleic acid; DTH = delayed-type hypersensitivity; FFPE = formalin fixed, paraffin 
embedded; PBMC = peripheral blood mononuclear cell; SNP = single nucleotide polymorphisms.  
a UV1 without sargramostim intradermally in the skin of the anterior forearm. Patient will measure and record the skin reaction 
48±4 hours after the injection. 
Table 10 
Extended Exploratory Cohort Assessments – Control Arm 
Abbreviations: DNA = deoxyribonucleic acid; FFPE = formalin fixed; paraffin embedded; PBMC = peripheral blood 
mononuclear cell; SNP = single nucleotide polymorphisms.  
Visit 
Assessment 
Volume of tissue collected  
Screening 
Fecal sample 
Tumor biopsy (FFPE biopsy) 
Tumor biopsy (Snap-frozen biopsy) 
Dedicated sample card 
At the pathologist’s decision (one biopsy) 
At the pathologist’s decision (two snap-frozen) 
Day 1 
Whole blood for DNA 
SNP sample 
Whole blood for PBMC 
3 mL blood 
3 mL blood 
80 mL blood 
Day 43  
Whole blood for PBMC 
80 mL blood 
Safety follow-up 
Whole blood for PBMC 
Tumor biopsy (FFPE biopsy) 
Tumor biopsy (Snap-frozen biopsy) 
80 mL blood 
At the pathologist’s decision (one biopsy) 
At the pathologist’s decision (two snap-frozen) 
18 weeks post last 
dose of induction 
therapy (2nd response 
follow-up visit) 
Whole blood for PBMC 
80 mL blood  
Total blood volume 
 
326 mL blood / patient 

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Sample Processing, Shipping, and Storage 
The study sites will receive a sampling kit and laboratory manual with instructions on sample 
collection and processing. Details on storage conditions will be provided in the laboratory 
manual. 
Assessments 
In the future, additional genes, biomarkers, and analysis methods of interest will most likely be 
identified. It is therefore important not to restrict the utilization of this biologic material to 
current knowledge and retain the possibility of conducting other investigations as well. However, 
based on current knowledge, it is planned to utilize the material in the manner described in the 
following sections. 
Whole Blood for DNA 
Exome sequencing of deoxyribonucleic acid (DNA) will be performed on blood samples 
collected before initiation of UV1 vaccination. The DNA from normal cells will serve as a basis 
for comparison to DNA sequence from tumor tissue, allowing to detect tumor-specific DNA 
alterations. 
Use/Analysis of DNA 
• Genetic variation may impact a patient’s response to therapy. Variable response to therapy 
may be due to genetic determinants that impact drug absorption, distribution, metabolism, 
and excretion; mechanism of action of the drug; disease etiology; and/or molecular 
subtype of the disease being treated. Therefore, where local regulations and Institutional 
Review Board/Independent Ethics Committee allow, a blood sample will be collected for 
DNA analysis. 
• DNA samples will be used for research related to sargramostim and/or UV1 or metastatic 
malignant melanoma. Genetic research may consist of the analysis of one or more 
candidate genes or the analysis of genetic markers throughout the genome in relation to 
sargramostim and/or UV1. 
• DNA samples will be analyzed as described in Section 8.4.1. Additional analyses may be 
conducted if it is hypothesized that this may help further understand the clinical data or 
help resolve issues with the clinical data. 
• The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to sargramostim and/or UV1 or study treatment of this class to 
understand study disease or related conditions. 
• The results of genetic analyses will be reported in a separate study addendum. 
• The Sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality. 

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• The samples will be retained while research on sargramostim and/or UV1 or study 
treatments of this class or indication continues but no longer than 5 years or other period 
as per local requirements. 
Whole Blood for Analyses of Single Nucleotide Polymorphisms (SNPs) 
Whole blood for analyses of SNPs will be taken prior to initiation of study treatment. Genomic 
DNA will be extracted and subsequently assessed for SNPs and other genetic variations in 
candidate genes that may predispose patients to benefit from the addition of UV1 vaccination to 
nivolumab and ipilimumab), or adverse events. Such genes include, but are not limited to 
hTERT, PD-1, PD-L1, PD-L2 and CTLA-4. Additional use of these data may include correlative 
analysis aimed at identifying genotypic associations with clinically relevant biomarkers 
identified by other methodologies. 
Whole Blood for Peripheral Blood Mononuclear Cells (PBMCs) 
Whole blood samples will be taken prior to initiation of study treatment and at designated 
timepoints for PBMC preparation. These samples may be used for immunophenotyping or 
characterization of the immune cell subsets in the periphery, including, but not limited to, T-cells, 
B cells, natural killer cells, myeloid-derived suppressor cells, or subpopulations of the 
aforementioned immune cell types. Additionally, these samples may be used for human 
leukocyte antigen typing, cytokine-release analyses, for functional immune cell tests, and 
characterization of the immune reactivity against tumor antigen. 
Tumor Tissue Specimens 
Tumor biopsies (formalin fixed, paraffin embedded [FFPE]) will form the basis for in situ 
characterization of the tumor and the tumor-microenvironment, including the tumor-infiltrating 
immune cells. The FFPE biopsies and snap-frozen biopsies will be used for DNA/RNA 
extraction and sequencing aiming at characterizing the immune contexture of the tumor, and to 
identify tumor-specific somatic mutations. 
The biopsies should be collected from the same lesion at each timepoint of sampling (ie, it 
should be taken into consideration when selecting the lesion for tissue sampling that the lesion 
may shrink in response to therapy). Since heterogeneity within tumors is an issue, it should be 
aimed at sampling within the same area of the lesion at each sampling timepoint. If a previous 
biopsy site is noted in the specimen to be sampled, the biopsies should be taken from near that 
site, but not from the exact site, as biopsies may alter the biology of adjacent tissue. If the patient 
has only one target lesion, the biopsy should be taken either subsequent or at least 7 days prior to 
the screening imaging scan. 
Biopsy samples should be excisional, incisional, or core needle. Punch biopsies are allowed as 
well. Fine needle aspirates or other cytology samples are only allowed after discussion with the 
Sponsor’s biomarker expert. Biopsies may be done with local anesthesia or conscious sedation. 
Institutional guidelines for the safe performance of biopsies should be followed. 
Detailed instructions of the obtaining, processing, labeling, handling, storage, and shipment of 
specimens will be provided in a separate Laboratory Manual. 

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Fecal Samples 
Fecal samples will be collected prior to treatment to evaluate the gut microbiome by use of PCR 
amplification of candidate gene sequences. Planned exploratory analyses are subject to changes 
in line with scientific understanding and technical development. 
Delayed-type Hypersensitivity 
Patients in the experimental arm will be asked to measure area of skin irritation on the skin of the 
anterior forearm and record it on a patient diary card (details to be explained to patient). This will 
be done 48 ±4 hours after each DTH test injection according to timepoints described in Table 9. 
A positive DTH test is defined as an erythema and/or induration ≥5 mm. The DTH patient diary 
card should be delivered to the study personnel at the next visit at the study site. 
If a patient prematurely discontinues induction therapy, no more DTH testing will be performed 
for that patient.  
 

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Appendix 3 Eastern Cooperative Oncology Group Performance Status Scale 
Eastern Cooperative Oncology Group Performance Status 
0 
Fully active, able to carry on all pre-disease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work 
of a light or sedentary nature (eg, light housework or office work). 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. 
Up and about more than 50% of waking hours. 
3 
Capable of only limited self-care; confined to bed or chair more than 50% of waking 
hours. 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair. 
5 
Dead. 
 

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Appendix 4 Response Evaluation Criteria in Solid Tumors and Immune Response Evaluation 
Criteria in Solid Tumors 
RECIST 1.1 Response and Evaluation Endpoints 
Measurable Disease. Measurable tumor lesions (nodal, subcutaneous, lung parenchyma, solid 
organ metastases) are defined as those that can be accurately measured in at least one dimension 
(longest diameter to be recorded) as ≥20 mm with chest x-ray and as ≥10 mm with computed 
tomography (CT) scan or clinical examination. Bone lesions are considered measurable only if 
assessed by CT scan and have an identifiable soft tissue component that meets these 
requirements (soft tissue component ≥10 mm by CT scan). Malignant lymph nodes must be 
≥15 mm in the short axis to be considered measurable; only the short axis will be measured and 
followed. All tumor measurements must be recorded in millimeters (or decimal fractions of 
centimeters). Previously irradiated lesions are not considered measurable unless progression has 
been documented in the lesion. 
Non-measurable Disease. All other lesions (or sites of disease), including small lesions, are 
considered non-measurable disease. Bone lesions without a measurable soft tissue component, 
leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonis, 
inflammatory breast disease, lymphangitic involvement of lung or skin, and abdominal masses 
followed by clinical examination are all non-measurable. Lesions in previously irradiated areas 
are non-measurable, unless progression has been demonstrated. 
Target Lesions. When more than one measurable tumor 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, but in addition should be those that lend 
themselves to reproducible repeated measurements. Note that pathological nodes must meet the 
criterion of a short axis of ≥15 mm by CT scan and 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. At Baseline, the sum of the 
target lesions (longest diameter of tumor lesions plus short axis of lymph nodes: overall 
maximum of 5) is to be recorded. 
After Baseline, a value should be provided on the Case Report Form for all identified target 
lesions for each assessment, even if very small. If extremely small and faint lesions cannot be 
accurately measured but are deemed to be present, a default value of 5 mm may be used. If 
lesions are too small to measure and indeed are believed to be absent, a default value of 0 mm 
may be used. 
Non-target Lesions. All non-measurable lesions (or sites of disease) plus any measurable lesions 
over and above those listed as target lesions are considered non-target lesions. Measurements are 
not required but these lesions should be noted at Baseline and should be followed as “present” or 
“absent.”  

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Response. All patients will have their BEST RESPONSE from the start of study treatment until 
the end of treatment classified as outlined below: 
Complete Response (CR): disappearance of target and non-target lesions and normalization of 
tumor markers. Pathological lymph nodes must have short axis measures <10 mm (Note: 
continue to record the measurement even if <10 mm and considered CR). Residual lesions (other 
than nodes <10 mm) thought to be non-malignant should be further investigated (by cytology 
specialized imaging or other techniques as appropriate for individual cases) before CR can be 
accepted. Confirmation of response is only required in non-randomized studies. 
Partial Response (PR): at least a 30% decrease in the sum of measures (longest diameter for 
tumor lesions and short axis measure for nodes) of target lesions, taking as reference the baseline 
sum of diameters. Non-target lesions must be non-progressive disease (PD). Confirmation of 
response is only required in non-randomized studies. 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD taking as reference the smallest sum of diameters on study. 
Progressive Disease (PD): at least a 20% increase in the sum of diameters of measured lesions 
taking as references the smallest sum of diameters recorded on study (including baseline) AND 
an absolute increase of ≥5 mm. Appearance of new lesions will also constitute PD (including 
lesions in previously unassessed areas). In exceptional circumstances, unequivocal progression 
of non-target disease may be accepted as evidence of disease progression, where the overall 
tumor burden has increased sufficiently to merit discontinuation of treatment. Modest increases 
in the size of one or more non-target lesions are NOT considered unequivocal progression.  
iRECIST Response Assessment  
Overall response will be assessed using immune Response Evaluation Criteria in Solid Tumors 
(iRECIST). Immunotherapeutics may result in infiltration of immune cells leading to transient 
increase in the size in malignant lesions, or undetectable lesions becoming detectable. The 
criteria are identical to those of Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in 
many respects but have been adapted to account for instances where an increase in tumor burden, 
or the appearance of new lesions, does not reflect true tumor progression.  

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Key differences are described below.  
Comparison of RECIST 1.1 and iRECIST 
 
All responses defined using iRECIST criteria are designated with a prefix. The iRECIST 
timepoint and best overall responses will be recorded separately. 
Confirming progression 
Unlike RECIST 1.1, iRECIST requires the confirmation of progression and uses the terms iUPD 
(unconfirmed progression) and iCPD (confirmed progression). Confirmatory scans should be 
performed at least 4 weeks but no longer than 8 weeks after iUPD.  
iCPD is confirmed if further increase in tumor burden, compared to the last assessment, is seen 
as evidenced by one or more of the following: 
• Continued increase in tumor burden (from iUPD) where RECIST 1.1 definitions of 
progression had been met in target, non-target disease, or new lesions 
o Progression in target disease worsens with an increase of at least 5 mm in the 
absolute value of the sum  
o Continued unequivocal progression in non-target disease with an increase in 
tumor burden  
o Increase in size of previously identified new lesion(s) (an increase of at least 
5 mm in the absolute value of the sum of those considered to be target new 
lesions) or additional new lesions.  

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• RECIST 1.1 criteria are met in lesions types (target, non-target, or new lesions) where 
progression was not previously identified, including the appearance of additional new 
lesions. 
If iUPD is not confirmed at the next assessment, then the appropriate response will be assigned 
(iUPD if the criteria are still met, but no worsening, or immune stable disease [iSD], immune 
partial response [iPR], or immune complete response [iCR] if those criteria are met compared to 
Baseline). Prior documentation of iUPD does not preclude assigning iCR, iPR, or iSD in 
subsequent timepoint assessments or as best overall response providing that iCPD is not 
documented at the next assessment after iUPD. 
New lesions 
New lesions should be assessed and measured as they appear using RECIST 1.1 criteria 
(maximum of 5 lesions, no more than 2 per site), at least 10 mm in long axis (or 15 mm in short 
axis for nodal lesions), and recorded as New Lesions-Target (NLT) and New Lesion-Non-Target 
(NLNT) to allow clear differentiation from Baseline target and non-target lesions. 
New lesions may either meet the criteria of NLT or NLNT to drive iUPD (or iCPD). However, 
the measurements of target lesions should NOT be included in the sum of measures of original 
target lesions identified at Baseline. Rather, these measurements will be collected on a separate 
table in the Case Report Form. 
Progressive disease is confirmed in the New Lesion category if the next imaging assessment, 
conducted at least 4 weeks (but not more than 8 weeks) after iUPD, confirms further progression 
from iUPD with either an increase of at least 5 mm in the absolute value of the sum of NLT OR 
an increase (but not necessarily unequivocal increase) in the size of NLNT lesions OR the 
appearance of additional new lesions.  
 
 

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Appendix 5 Abbreviations 
AE 
adverse event 
AESI 
adverse events of special interest  
ADL 
Activities of Daily Living 
ALT 
alanine aminotransferase  
ANC 
absolute neutrophil count  
AST 
aspartate aminotransferase  
BICR 
Blinded Independent Central Review 
BRAF 
Gene encoding B-Raf protein 
BUN 
blood urea nitrogen 
CFR 
Code of Federal Regulations  
CI 
confidence interval 
CNS 
central nervous system  
CR 
complete response  
CRO 
Contract Research Organization 
CT 
computed tomography  
CTLA-4 
anti-cytotoxic T-lymphocyte-associated protein-4  
DILI 
drug induced liver injury 
DNA 
deoxyribonucleic acid 
DOR 
duration of response  
DTH 
delayed-type hypersensitivity  
ECOG 
Eastern Cooperative Oncology Group  
eCRF 
electronic Case Report Form 
EOS 
end of study 
FDA 
Food and Drug Administration 
FFPE 
formalin fixed, paraffin embedded  
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
GM-CSF  
granulocyte-macrophage colony-stimulating factor 
hTERT 
human telomerase reverse transcriptase  
GOT 
glutamic-oxaloacetic transaminase  
GPT 
glutamic-pyruvic transaminase 
HIV 
human immunodeficiency virus 
HR 
hazard ratio  

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HRT 
hormonal replacement therapy 
IB 
Investigator’s Brochure  
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IMP 
investigational medicinal product 
IRB 
Institutional Review Board 
ITT 
intention-to-treat 
iCPD 
immune confirmed progressive disease 
iCR 
immune complete response 
iPR 
immune partial response 
iRECIST 
immune RECIST 
iSD 
immune stable disease 
iUPD 
immune unconfirmed progressive disease 
IWRS 
interactive web response system 
MedDRA 
Medical Dictionary for Regulatory Activities 
MEK 
mitogen-activated protein kinase  
MRI 
magnetic resonance imaging  
NE 
non-evaluable  
NIMP 
non-investigational medicinal product 
NLNT 
New Lesion-Non-Target 
NLT 
New Lesions-Target 
NSCLC 
non-small cell lung cancer  
ORR 
objective response rate  
OS 
overall survival  
PBMC 
peripheral blood mononuclear cell 
PD 
progressive disease 
PD-1 
anti-programmed cell death 
PFS 
progression free survival  
PR 
partial response  
RBC 
red blood cells 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
ribonucleic acid 
Q2W 
every 2 weeks 
Q3W 
every 3 weeks 

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Q4W 
every 4 weeks 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
stable disease  
SNPs 
single nucleotide polymorphisms  
SUSAR 
suspected unexpected serious adverse reaction 
TCR 
T-cell receptor 
TEAE 
treatment-emergent adverse event 
Th1 
T-helper type 1 
TMB 
tumor mutational burden 
TSH 
thyroid-stimulating hormone  
ULN 
upper limit of normal  
WBC 
white blood cells 
WOCBP 
women of childbearing potential 
 

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Appendix 6 References 
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer 
statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 
36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. 
2. Ascierto PA, Simeone E, Sileni VC, et al. Clinical experience with ipilimumab 3 mg/kg: 
real-world efficacy and safety data from an expanded access programme cohort. J Transl 
Med. 2014 May 7;12:116.  
3. Ahmad SS, Qian W, Ellis S, et al. Ipilimumab in the real world: the UK expanded access 
programme experience in previously treated advanced melanoma patients. Melanoma 
Res. 2015;25(5):432-442. 
4. Robert C, Schachter J, Long GV, et al. Pembrolizumab versus Ipilimumab in Advanced 
Melanoma. N Engl J Med. 2015 Jun 25;372(26):2521-2532. 
5. Schachter J, Ribas A, Long GV, et al. Pembrolizumab versus ipilimumab for advanced 
melanoma: final overall survival results of a multicentre, randomised, open-label 
phase 3 study (KEYNOTE-006). Lancet. 2017;390(10105):1853-1862. 
6. Hamid O, Puzanov I, Dummer R, et al. Final analysis of a randomised trial comparing 
pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory 
advanced melanoma. Eur J Cancer. 2017;86:37-45. 
7. Hodi FS, O'Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients 
with metastatic melanoma. N Engl J Med. 2010;363(8):711-723. 
8. Hersh EM, O'Day SJ, Powderly J, et al. A phase II multicenter study of ipilimumab with 
or without dacarbazine in chemotherapy-naïve patients with advanced melanoma. Invest 
New Drugs. 2011;29(3):489-498. 
9. Wilgenhof S, Du Four S, Vandenbroucke F, et al. Single-center experience with 
ipilimumab in an expanded access program for patients with pretreated advanced 
melanoma. J Immunother. 2013;36(3):215-222. 
10. Ascierto PA, Del Vecchio M, Robert C, et al. Ipilimumab 10 mg/kg versus ipilimumab 
3 mg/kg in patients with unresectable or metastatic melanoma: a randomised, 
double-blind, multicentre, phase 3 trial. Lancet Oncol. 2017;18(5):611-622. 
11. Robert C, Long GV, Brady B, et al. Nivolumab in previously untreated melanoma 
without BRAF mutation. N Engl J Med. 2015 Jan 22;372(4):320-330. 
12. Hamid O, Puzanov I, Dummer R, et al. Final analysis of a randomised trial comparing 
pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory 
advanced melanoma. Eur J Cancer. 2017;86:37-45. 
13. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined Nivolumab and Ipilimumab or 
Monotherapy in Untreated Melanoma. N Engl J Med. 2015 Jul 2;373(1):23-34.  
14. Hodi FS, Chiarion-Sileni V, Gonzalez R, et al. Nivolumab plus ipilimumab or nivolumab 
alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year 
outcomes of a multicentre, randomised, phase 3 trial. Lancet Oncol. 2018 
Nov;19(11):1480-1492. doi: 10.1016/S1470-2045(18)30700-9. Epub 2018 Oct 22. 

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15. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Five-year survival with combined 
nivolumab and ipilimumab in advanced melanoma. N Engl J Med. 2019 Oct 
17;381(16):1535-1546. 
16. Vasef MA, Ross JS, Cohen MB. Telomerase activity in human solid tumors. Diagnostic 
utility and clinical applications. Am J Clin Pathol. 1999;112(1 Suppl 1): S68-75. 
17. Mattson MP, Zhang P, Fu W. Roles for TERT and telomerase in cell differentiation and 
apoptosis. Madame Curie Bioscience Database [Internet]. 2000-2013. 
18. Hiyama E, Hiyama K, Yokoyama T, Shay JW. Immunohistochemical detection of 
telomerase (hTERT) protein in human cancer tissues and a subset of cells in normal 
tissues. Neoplasia. 2001;3(1):17-26. 
19. Kim NW, Piatyszek MA, Prowse KR, et al. Specific association of human telomerase 
activity with immortal cells and cancer. Science. 1994;266(5193):2011-2015. 
20. Zanetti M. A second chance for telomerase reverse transcriptase in anticancer 
immunotherapy. Nat Rev Clin Oncol. 2017;14(2):115-128. 
21. de Kok JB, Ruers TJ, van Muijen GN, et al. Real-time quantification of human 
telomerase reverse transcriptase mRNA in tumors and healthy tissues. Clin Chem. 
2000;46(3):313-318. 
22. Inderberg-Suso EM, Trachsel S, Lislerud K, Rasmussen AM, Gaudernack G. Widespread 
CD4+ T-cell reactivity to novel hTERT epitopes following vaccination of cancer patients 
with a single hTERT peptide GV1001. Oncoimmunology. 2012;1(5):670-686. 
23. Suso EM, Dueland S, Rasmussen AM, et al. hTERT mRNA dendritic cell vaccination: 
complete response in a pancreatic cancer patient associated with response against several 
hTERT epitopes. Cancer Immunol Immunother. 2011 Jun;60(6):809-818. 
24. Disis ML, Bernhard H, Shiota FM, et al. Granulocyte-macrophage colony-stimulating 
factor: an effective adjuvant for protein and peptide-based vaccines. Blood. 1996;88(1): 
202-210. 
25. Kaplan G, Walsh G, Guido LS, et al. Novel responses of human skin to intradermal 
recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell 
recruitment, keratinocyte growth, and enhanced wound healing. J Exp Med. 1992;175(6): 
1717-1728. 
26. Kremer IB, Stevens SR, Gould JW, DiCarlo J, Quinby GE, Cooper KD. Intradermal 
granulocyte-macrophage colony-stimulating factor alters cutaneous antigen-presenting 
cells and differentially affects local versus distant immunization in humans. Clin 
Immunol. 2000;96(1):29-37. 
27. Lilleby W, Gaudernack G, Brunsvig PF, et al. Phase I/IIa clinical trial of a novel hTERT 
peptide vaccine in men with metastatic hormone-naive prostate cancer. Cancer Immunol 
Immunother. 2017 Jul;66(7):891-901.  
28. Brunsvig PF, Aamdal S, Gjertsen MK, et al. Telomerase peptide vaccination: a phase I/II 
study in patients with non-small cell lung cancer. Cancer Immunol Immunother. 
2006;55(12):1553-1564. 

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29. Kyte JA, Trachsel S, Risberg B, thor Straten P, Lislerud K, Gaudernack G. 
Unconventional cytokine profiles and development of T cell memory in long-term 
survivors after cancer vaccination. Cancer Immunol Immunother. 
2009;58(10):1609-1626. 
30. Buchbinder EI, Desai A. CTLA-4 and PD-1 pathways: similarities, differences, and 
implications of their inhibition. Am J Clin Oncol. 2016 Feb;39(1):98-106. 
31. Wei SC, Levine JH, Cogdill AP, et al., Distinct cellular mechanisms underlie anti-CTLA-
4 and anti-PD-1 checkpoint blockade. Cell. 2017;170(6):1120-1133. 
32. Ellis S, Carroll KJ, Pemberton K. Analysis of duration of response in oncology trials. 
Contemp Clin Trials. 2008;29(4):456-465. 
33. Perez-Garcia A, Osca G, Bosch-Vizcaya A, et al. Kinetics of the CTLA-4 isoforms 
expression after T-lymphocyte activation and role of the promoter polymorphisms on 
CTLA-4 gene transcription. Hum Immunol. 2013;74(9):1219-1224. 
34. Doyle AM, Mullen AC, Villarino AV, Hutchins AS, High FA, Lee HW, et al. Induction 
of cytotoxic T lymphocyte antigen 4 (CTLA-4) restricts clonal expansion of helper 
T cells. J Exp Med. 2001 Oct 1;194(7):893–902. 
 
 
 

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Appendix 7 Single Arm UV1 Cohort 
Background and Rationale 
Patients participating in the Extended Exploratory cohort of the study (Appendix 2) provide 
biological sample material including PBMCs and tumor tissue to answer the exploratory 
objectives of the INITIUM study. The material is used to test for immune response in blood and 
to characterize changes in the tumor and the tumor microenvironment. The PBMCs and tumor 
tissue from patients in the experimental arm of the extended exploratory cohort is needed for 
these analyses, as this material is used to identify changes in the tumor and tumor environment 
that are unique for the vaccine responders.   
As an immunological response to the vaccine is not expected in all patients in the experimental 
arm of the extended exploratory cohort, and as all patients in this arm will not be able to provide 
a complete set of biological sample material, 20 additional patients will be enrolled in a single 
arm UV1 cohort and provide additional biological material to support the extended exploratory 
cohort. This will be done to secure that sufficient material is available to identify anti-tumor 
activity unique for the vaccine responders and thereby to strengthen the support from the 
mechanistical data to the clinical outcome data derived from all patients in the study. 
Design and Methodology 
20 patients at selected sites will be included in a single arm UV1 cohort. The inclusion of 
patients in this cohort will start after the 154 patients have been enrolled in the 2-armed 
randomized part of the study. All patients in this single arm UV1 cohort will receive UV1 
vaccination in combination with nivolumab and ipilimumab.  
If not described otherwise in Appendix 7, the patients will follow the same treatment schedule, 
visits and procedures as in the experimental arm described elsewhere in this study protocol. In 
addition, all patients in the single arm UV1 cohort will perform the biological sampling and 
procedures as described for the Extended Exploratory Cohort (Appendix 2). The patients will 
have to sign a separate Informed Consent Form (ICF) to enroll in this part of the study.  
As in the randomized part of the study, this single arm UV1 cohort will consist of 3 phases: 
Screening, Induction period and a Follow-up period. The Follow-up period includes safety, 
response, and survival follow-up visits. The Response Follow-up visits will be performed until 
iCPD per iRECIST or until the end of study (whichever comes first). The Survival Follow-visits 
will be performed every 12 weeks from iCPD per iRECIST until the end of study. 
Patients in the single arm UV1 cohort will not be randomized and will therefore not be included 
in the data used for analysis of primary and secondary endpoints.  
Planned Timelines for the Single Arm UV1 Cohort: 
First patient in: 
 
 
 
 
 
H1 2022 
Last patient in:  
 
 
 
 
 
H1 2023 

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End of study:   
 
 
 
 
 
H1 2026 
The first patient in is defined as the timepoint when the first patient is enrolled.  
The estimated inclusion period is 9 months. All patients in the single arm UV1 cohort will be 
followed up until death or until the end of study (EOS), whichever comes first.  
Target Population 
Patients in the single arm UV1 cohort must meet all the inclusion criteria and none of the 
exclusion criteria as described in Sections 5.1 and 5.2. Only selected study sites that have the 
necessary laboratory facilities to collect and handle the requested lab samples can take part in 
this cohort.  
After the patient has signed the ICF, the site will enter information into the IWRS which will 
assign a unique screening number. Once assigned, a screening number cannot be re-used for any 
reason. After a screening period of up to 28 days, eligible patients will be enrolled in the study 
using IWRS. Individuals who do not meet the criteria for enrollment (screen failures) may be 
re-screened once. Re-screened patients should be assigned a new screening number and 
re-consent. 
Discontinuation from the Single Arm UV1 Cohort  
Patients can withdraw their single arm UV1 cohort consent at any time without this affecting 
their care and treatment. The patient can request all samples collected under this consent to be 
destroyed. Results from samples already analyzed will not be deleted. 
Sample Processing, Shipping, and Storage 
The study sites will use the same laboratory manual and sampling kits as applicable for Extended 
Exploratory cohort. Details regarding sample collection, processing and storage conditions will 
be provided in the laboratory manual. 
Adverse Event Reporting 
The time periods for reporting of AEs and SAEs are outlined in Figure 4.  
In the single arm UV1 cohort all SAEs should be reported from the first dose of induction 
therapy until the end of study or until new anticancer treatment is initiated (whichever comes 
first).   

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Appendix 8 Protocol Version Log 

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Protocol version 5.0 
22 September 2023 
Changes 
Substantial 
amendment: Yes 
Amended the protocol to modify the timing of reading the primary 
endpoint at 70 PFS events reached, to the earliest of either 70 PFS events 
reached or 18 months post last patient randomized.  
 
Updated sections: 
1 Synopsis 
4.1 Overall Design 
6.2.3 New Anticancer Treatment 
Table 5 Schedule of Activities – Experimental arm 
Table 6 Schedule of Activities – Control arm 
7.3.2 Response Follow-up Visits 
7.3.3 Survival Follow-up Visits 
7.6 End of Study 
8.2 Safety Plan and Assessments 
8.2.1 Independent Data Monitoring Committee 
8.3.3 Adverse Event Reporting and Follow-up 
9 Statistical Methods 
 
Amended the protocol to include updated information about the 
UV1/hTERT-MM-103 study (Ultimovacs is the sponsor) 
 
Updated sections: 
2.4 Clinical Data on UV1 Vaccination 
2.6 Rationale for Dose and Administration Regimen 
2.8 Benefit/Risk Assessment 
 
Amended the protocol to include non-substantial amendment version 3.0, 
dated 14 December 2022: an amendment to ensure that the blinded 
independent central review (BICR) receives the required images needed 
for determination of progression per RECIST 1.1. 
 
Updated section: 
7.3.2 Response Follow-up Visits 
Protocol version 4.0 
21 January 2022 
Changes 

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Substantial 
amendment: Yes 
Amended the protocol to include non-substantial protocol amendment 
version 1.0, dated 24 February 2021: a clarification of the measurements 
that are expected per protocol in the case of severe allergic reactions 
(Adverse Events of Special Interests). 
 
Updated sections: 
8.3.3.2 Follow-up 
 
Amended the protocol to include non-substantial protocol amendment 
version 2.0, dated 07 September 2021: a clarification of prohibited 
medications during the induction period and which measurements that are 
expected in the case of discontinuation of induction therapy.  
 
Updated sections: 
6.2.1 Prohibited Medications During Induction Period 
7.2.1 Discontinuation of Induction Therapy 
 
Amended the protocol to mitigate the risk of hepatotoxicity in the study. 
Updated sections: 
Table 5 Schedule of Activities – Experimental arm 
Table 6 Schedule of Activities – Control arm 
8.2.1 Independent Data Monitoring Committee 
 
Amended the protocol to include the single arm UV1 cohort where 
20 patients will be enrolled for collection of additional biological material 
to support the Extended Exploratory Cohort of the study. 
 
Updated sections: 
1 Synopsis 
2.7 Rationale for Study Design 
4.1 Overall Design 
4.2 Measures to Minimize Bias: Randomization and Blinding 
8.2.1 Independent Data Monitoring Committee 
Appendix 7 Single arm UV1 cohort - NEW 
 
Name of International Coordinating Investigator updated due to change 
 
Updated section: 
Page 2 

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Updated planned timelines  
 
Updated sections: 
1 Synopsis 
4.1 Overall Design 
 
Table numbers corrected 
 
Updated section: 
6.1.5 Administration of Study Drug 
Protocol version 3.0 
02 November 2020 
Changes 
Substantial 
amendment: Yes 
Amended the protocol to reflect that from the time of 70 PFS events 
reached across both treatment arms, patients will be followed for a further 
24 months for additional survival data; further analyses of OS data will be 
performed at 12 and 24 months to provide evidence supportive of PFS. 
 
Updated sections: 
1 Synopsis 
4.1 Overall Design 
6.2.3 New anticancer treatment 
Table 5 Schedule of Activities – Experimental arm 
Table 6 Schedule of Activities – Control arm 
7.2.1 Discontinuation of Induction Therapy 
7.3.2 Response Follow-up visits 
7.3.3 Survival Follow-up visits 
7.6 End of study 
8.2 Safety plan and assessments 
8.3.3 Adverse event reporting and follow-up 
9 Statistical methods 
 
Signature for International Coordinating Investigator added 
 
Amended planned number of patients in the extended exploratory cohort 
from N = 60 to N = approximately 40   
Updated sections: 
1 Synopsis 
4.1 Overall Design 

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Table 5 Schedule of Activities – Experimental arm 
Table 6 Schedule of Activities – Control arm 
8.5 Extended exploratory cohort 
Appendix 1 Clinical Laboratory Tests 
Appendix 2 Extended exploratory cohort 
 
Text updated to clarify that Adverse Events of Special Interest should be 
reported regardless of which treatment arm the patient is randomized to. 
 
Text revised to clarify that events falling under the AESI definition must 
occur on the same day as sargramostim, UV1, nivolumab or ipilimumab 
administration.  
Updated section: 
8.3.1.5 Definition of adverse event of special interest 
 
Text revised to allow sites to use either plasma or serum for the 
biochemistry analyses and pregnancy test.  
 
Updated sections: 
1 Synopsis (Inclusion Criteria) 
5.1 Inclusion Criteria 
8.3.1.4 Potential Drug Induced Liver Injury (DILI) 
Appendix 1 Clinical Laboratory Tests 
 
Text updated to reflect the planned number of study sites in Europe and 
the United States  
Updated section: 
1 Synopsis 
4.1 Overall Design 
 
Text updated to clarify that unused portions of reconstituted sargramostim 
should be discarded. 
Updated section: 
6.1.1 Sargramostim 
 
Text updated to clarify the visit scenario if a decision to discontinue 
induction therapy is done between two scheduled study visits. 
Clarification made on when to discontinue UV1 vaccination. 

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Updated section: 
7.2.1 Discontinuation of induction therapy 
 
Text updated to clarify the definition of the “end of study” 
Updated section: 
7.6 End of study 
 
Text updated to clarify that a brief course of corticosteroids can be 
allowed even with doses >10 mg/day prednisone equivalents 
Updated section: 
1 Synopsis (Exclusion Criteria) 
5.2 Exclusion Criteria 
6.2.2 Permitted medications during induction period 
 
Text updated to clarify what is defined as “completed treatment cycle” 
 
Updated section: 
8.2.1 Independent Data Monitoring Committee 
 
Typing error corrected from “will be stratified” to “covariates” 
Updated section: 
9.4.2.2 Secondary efficacy analyses 
Protocol version 2.1 
20 February 2020 
Changes 
Substantial 
amendment: No 
Text revised to clarify that all SAEs should be reported until end of study 
or until new anticancer treatment is initiated (whichever comes first) 
 
Updated sections: 
1 Synopsis 
4.1 Overall Design 
7 Study Duration and Schedule of Activities:  
Table 5 Schedule of Activities – Experimental arm 
Table 6 Schedule of Activities – Control arm 
7.2.1 Discontinuation of Induction Therapy 
8.3.3.1 Reporting and Figure 3 

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Clarification of when a vasectomized partner is an acceptable highly 
effective contraception method 
 
Updated sections: 
1 Synopsis (Inclusion Criteria) 
5.1 Inclusion Criteria 
 
Typing error corrected from “iPD” to “iCPD” 
 
Updated section: 
7.3.3 Survival Follow-up Visits 
 
Minor typing errors corrected 
 
Updated section: 
Appendix 7 Protocol Version Log 
Protocol version 2.0 
27 January 2020 
Changes 
Substantial 
amendment: Yes 
Amended safety data collection. Revised to include collection of all 
serious AESIs until the end of the study, in both treatment arms, and 
regardless of the investigator’s causality assessment 
Updated sections: 
1 Synopsis 
4.1 Overall design 
7 Study Duration and Schedule of Activities:  
Table 5 Schedule of Activities – Experimental arm 
Table 6 Schedule of Activities – Control arm 
7.2.1 Discontinuation of Induction Therapy 
8.3.1.5 Definition of Adverse Event of Special Interest 
8.3.3.1 Reporting and Figure 3 
Amended to accurately describe what is highly effective contraceptive 
methods 
Updated sections: 
1 Synopsis (Inclusion Criteria) 
5.1 Inclusion Criteria 

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The IDMC meeting schedule has been amended with an additional third 
meeting and to allow for review of patients in both treatment arms. The 
primary responsibility of the IDMC has been more clearly described. 
Updated section: 
8.2.1 Independent Data Monitoring Committee 
Text revised to align with the wording used for BRAF/MEK inhibitors in 
section 5.2 exclusion criteria 
Updated section: 
1 Synopsis (the exclusion criteria) 
Text revised to clarify that Overall Survival will be analyzed at the end of 
the study, which is defined by having reached 70 PFS endpoints across 
both study arms. 
Updated sections: 
1 Synopsis 
9.5 Timing of Analyses (new section) 
Clarification that the UV1 vaccination will be permanently discontinued if 
nivolumab and/or ipilimumab is temporarily or permanently discontinued. 
Updated section: 
7.2.1 Discontinuation of Induction Therapy 
Text revised to clarify that patients who continue with survival follow-up 
visits will be contacted per phone (or, at the Investigator’s discretion visit 
the hospital) 
Updated sections:  
1 Synopsis (study design and methodology) 
4.1 Overall design 
7 Study Duration and Schedule of Activities:  
Table 5 Schedule of Activities – Experimental arm 
Table 6 Schedule of Activities – Control arm 
7.3.3 Survival Follow-up visits 
Text revised to clarify the timing of the biopsy sampling at screening 
Updated sections:  
7 Study Duration and Schedule of Activities:  
Table 5 Schedule of Activities – Experimental arm 

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Table 6 Schedule of Activities – Control arm 
Appendix 2, Tumor Tissue Specimen 
Text revised to reflect that the patient may continue with maintenance 
therapy if withdrawing the informed consent form 
Updated section: 
7.4 Withdrawal of Consent  
Deleted collection of respiratory rate. 
Updated section: 
8.2.3 Vital Signs 
Clarification of what is considered a clinically significant laboratory 
abnormality. 
 
Updated sections: 
8.3.1.1 Definition of AE 
8.3.1.2 Events Not Meeting the AE Definition 
Deleted and revised Clinical Study Protocol signature/declaration pages to 
reflect the signature roles required 

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Declaration of the National Coordinating Investigator 
Title: A Randomized Phase II, Open-label, Active-controlled, Multicenter Study Investigating 
the Efficacy and Safety of UV1 Vaccination in Combination with Nivolumab and Ipilimumab as 
First-line Treatment of Patients with Unresectable or Metastatic Melanoma (UV1-202) 
This study protocol was subjected to critical review and has been approved by the Sponsor. The 
information it contains is consistent with the current risk/benefit evaluation of the investigational 
product as well as with the moral, ethical, and scientific principles governing clinical research as 
set out in the Declaration of Helsinki, as amended in October 2013 and the guidelines on Good 
Clinical Practice. 
National Coordinating Investigator 
 
_____________________________________ 
_____________________ 
Signature 
Date 
_____________________________________ 
Name (block letters) 
_____________________________________ 
Title (block letters) 
_____________________________________ 
Institution (block letters) 
_____________________________________ 
Phone number 
 
 

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Declaration of the Principal Investigator 
Title: A Randomized Phase II, Open-label, Active-controlled, Multicenter Study Investigating 
the Efficacy and Safety of UV1 Vaccination in Combination with Nivolumab and Ipilimumab as 
First-line Treatment of Patients with Unresectable or Metastatic Melanoma (UV1-202) 
All documentation for this study that is supplied to me and that has not been previously 
published will be kept in the strictest confidence. This documentation includes this study 
protocol, Investigator's Brochure, electronic Case Report Form, and other scientific data. 
The study will not be commenced without the prior written approval of a properly constituted 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC). No changes will be 
made to the study protocol without the prior written approval of the Sponsor and the IRB or IEC, 
except where necessary to eliminate an immediate hazard to the participants. 
I have read, understood, and agree to abide by all the conditions and instructions contained in 
this protocol. 
Responsible Principal Investigator of the local study center 
 
_____________________________________ 
_____________________ 
Signature 
Date 
_____________________________________ 
Name (block letters) 
_____________________________________ 
Title (block letters) 
_____________________________________ 
Institution (block letters) 
_____________________________________ 
Phone number