Clinical trial NCT02432846
Conditions: Renal Cell Carcinoma, Metastatic
Sponsor: Mendus
Start date: 2015-04-01; Completion date: 2021-01-31
Enrollment: 88 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to compare tumor response, progression free survival (PFS) and overall survival (OS) in newly diagnosed mRCC patients treated with Intuvax (INN: ilixadencel) pre-nephrectomy followed by Sunitinib post-nephrectomy vs Sunitinib post-nephrectomy patients.

Detailed description:
Patients, all planned for nephrectomy, will be stratified according to the Heng risk criteria (high risk patients vs. intermediate risk patients) and randomized in a 2:1 ratio to receive Intuvax (INN: ilixadencel)+ Sunitinib or Sunitinib alone.

Two doses of Intuvax (INN: ilixadencel) will be administered in to the primary tumour before nephrectomy. The control group will be scheduled for nephrectomy directly.

All patients will start Sunitinib treatment 5-8 weeks after operation.

Results from the phase I study, together with the results reported in the literature on the use of autologous dendritic cells (DCs) in combination with Sunitinib encourage Immunicum aktiebolag (AB) to further investigate the possibility of exploiting Intuvax (INN: ilixadencel) 10 million cells/dose when combined with Sunitinib for the treatment of mRCC patients.

Arms: arm 1: Two Intuvax (INN: ilixadencel) doses (10 million cells/dose) 14 days apart before nephrectomy, followed by Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening). arm 2: Sunitinib treatment post-nephrectomy according to clinical practice until RECIST verified progressive disease or End-of-Study (78 weeks after screening).
Interventions: intervention 1: Intuvax (INN: ilixadencel) intervention 2: Sunitinib
Intervention descriptions: intervention 1: Therapeutic dose (10 million cells/dose): allogeneic, pro-inflammatory dendritic cells. intervention 2: Cytostatic/cytotoxic drug: protein kinase inhibitor .

Protocol documents:
Prot_000.pdf: 
Official Title: Clinical Study Protocol  
An open-label, randomized, controlled, multicenter, phase II study evaluating safety and efficacy of 
intratumorally administered Intuvax pre-nephrectomy followed by Sunitinib post-nephrectomy, 
compared to Sunitinib post-nephrectomy in metastatic renal cell carcinoma patients 
 
Document date: 12 February 2019 
 
NCT number: NCT02432846 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 2 of 87 
1 
SYNOPSIS 
Name of the Sponsor/Company: 
Immunicum AB (publ) 
Study Code:  
IM-201 
Name of Investigational Medicinal Product: 
Intuvax 
EudraCT No.:  
2014-004510-28 
Development Phase of the Study: 
Phase II 
Trial under an IND:  
IND No.: 17081 
TITLE OF THE STUDY: An open-label, randomized, controlled, multicenter, phase II study evaluating 
safety and efficacy of intratumorally administered Intuvax pre-nephrectomy followed by Sunitinib post-
nephrectomy, compared to Sunitinib post-nephrectomy in metastatic renal cell carcinoma patients 
OBJECTIVES: 
The primary objectives are: 
• 
To evaluate median overall survival (OS) from randomization in metastatic renal cell carcinoma 
(mRCC) patients overall and by subgroup, i.e. in high-risk and in intermediate-risk patients 
separately, receiving two (2) vaccine doses of Intuvax pre-nephrectomy, followed by sunitinib 
initiated five (5) to eight (8) weeks post-nephrectomy and in non-vaccinated mRCC patients 
receiving sunitinib initiated five (5) to eight (8) weeks post-nephrectomy 
• 
To evaluate 18-month survival rate from randomization in mRCC patients overall and by 
subgroup, i.e. in high-risk and in intermediate-risk patients separately, receiving two (2) vaccine 
doses of Intuvax pre-nephrectomy followed by sunitinib post-nephrectomy and in non-
vaccinated patients receiving sunitinib post-nephrectomy 
The secondary objectives are: 
• 
To evaluate safety and tolerability in high- and intermediate-risk mRCC patients receiving two 
(2) vaccine doses of Intuvax pre-nephrectomy followed by sunitinib post-nephrectomy and in 
non-vaccinated patients receiving sunitinib post-nephrectomy 
• 
To evaluate progression free survival (PFS) according to Response Evaluation Criteria in Solid 
Tumors (RECIST) 1.1 criteria from Sunitinib Start Visit in intermediate- and high-risk mRCC 
patients after receiving two (2) vaccine doses of Intuvax pre-nephrectomy followed by sunitinib 
post-nephrectomy and in non-vaccinated patients receiving sunitinib post-nephrectomy* 
• 
To evaluate response and its duration according to RECIST 1.1 criteria from Sunitinib Start Visit 
in intermediate- and high-risk mRCC patients receiving two (2) vaccine doses of Intuvax 
pre-nephrectomy followed by sunitinib post-nephrectomy and in non-vaccinated patients 
receiving sunitinib post-nephrectomy* 
• 
To evaluate time to progression (TTP) from Sunitinib Start Visit in intermediate- and high-risk 
mRCC patients receiving two (2) vaccine doses of Intuvax pre-nephrectomy followed by 
sunitinib post-nephrectomy and in non-vaccinated patients receiving sunitinib post-
nephrectomy* 
• 
To evaluate the number of infiltrating CD8+ T-cells in available diagnostic pre-biopsy (sample 
from either primary tumor or metastasis acceptable) and in the resected primary renal tumor in 
intermediate- and high-risk mRCC patients receiving two (2) vaccine doses of Intuvax 
pre-nephrectomy and in non-vaccinated patients 
*Note: For intermediate-risk patients included in the trial according to protocol versions before 
version Final 4.0, baseline for PFS, response and its duration, and TTP is defined as the first 
imaging assessment after nephrectomy. 
 
 
 




Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 4 of 87 
Name of the Sponsor/Company: 
Immunicum AB (publ) 
Study Code:  
IM-201 
Name of Investigational Medicinal Product: 
Intuvax 
EudraCT No.:  
2014-004510-28 
Development Phase of the Study: 
Phase II 
Trial under an IND:  
IND No.: 17081 
INVESTIGATIONAL MEDICINAL PRODUCT: 
Intuvax (a cryopreserved dendritic cell suspension of 11.7 x106 viable and Human Leukocyte Antigen 
(HLA) class II expressing cells in 1 mL heat-inactivated AB plasma, supplemented with 10% dimethyl 
sulfoxide [DMSO]). 
Sunitinib (marketed products). 
NUMBER OF PATIENTS: 
Approximately 90 patients (with a stratification of intermediate-risk versus high-risk patients at 
randomization). 
NUMBER OF STUDY CENTERS: 
Approximately 25 sites in EU and approximately 5 sites in US 
MAIN INCLUSION AND EXCLUSION CRITERIA: 
Inclusion criteria: 
1) 
Newly (<6 months) diagnosed RCC (histological/cytological verification is optional) with at least 
one (1) CT-verified metastasis ≥10 mm for which complete metastasectomy is not planned. US 
patients must have verified clear-cell tumor histology 
2) 
Planned resection of primary tumor 
3) 
Primary tumor diameter ≥40 mm 
4) 
Candidate for first-line therapy with sunitinib initiated five (5) to eight (8) weeks after nephrectomy 
5) 
Female or male ≥18 years of age 
6) 
Willing and able to provide informed consent 
7) 
Adequate hematological parameters, i.e.: 
• 
B-Leukocyte count ≥4.5 x109/L 
• 
B-Platelet count ≥150 x109/L 
• 
B-Hemoglobin (Hb) ≥90 g/L 
8) 
Serum-creatinine and serum-bilirubin ≤1.5 × ULN. Serum-ALAT and serum-ASAT ≤2.5 × ULN (or 
≤5 in case of liver metastases) 
9) 
Female who has been post-menopausal for more than one (1) year or female of childbearing 
potential agreeing to use a highly efficient method of contraception (i.e. a method with less than 
1% failure rate [e.g. sterilization, hormone implants, hormone injections, some intrauterine 
devices, or vasectomized partner or combined birth control pills]) from Screening until 90 days 
after last dose of Intuvax and/or until completed sunitinib treatment whichever occurs later. 
Female of childbearing potential must have a negative blood pregnancy test at Screening, and if 
randomized to vaccination a negative blood or urine pregnancy test within one (1) day before 
each dose of Intuvax) and must not be lactating 
 
or 
 
Male agreeing to use condoms from Screening until 90 days after last dose of Intuvax and/or until 
completed sunitinib treatment whichever occurs later, or male having a female partner who is 
using a highly efficient method of contraception as described above 
Exclusion criteria: 
1) 
Life expectancy less than 4 months 


Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 5 of 87 
Name of the Sponsor/Company: 
Immunicum AB (publ) 
Study Code:  
IM-201 
Name of Investigational Medicinal Product: 
Intuvax 
EudraCT No.:  
2014-004510-28 
Development Phase of the Study: 
Phase II 
Trial under an IND:  
IND No.: 17081 
2) 
Central nervous system (CNS) metastasis that is symptomatic or progressing or untreated or that 
requires current therapy (e.g. evidence of new or enlarging CNS metastasis or new neurological 
symptoms attributable to CNS metastases) 
3) 
Active autoimmune disease which requires treatment with systemic immunosuppressive agents, 
e.g. inflammatory bowel disease, multiple sclerosis, sarcoidosis, psoriasis, autoimmune hemolytic 
anemia, rheumatoid arthritis, SLE, vasculitis, Sjögren's syndrome, scleroderma, autoimmune 
hepatitis, and other rheumatological diseases 
4) 
Treatment with per oral systemic corticosteroids exceeding 10 mg/day within 7 days before 
Screening until Nephrectomy (inhaled, intranasal, and local steroids acceptable 
irrespective of dose) 
5) 
Known cardiomyopathy and/or clinically significant abnormal ECG findings at Screening 
disqualifying the patient from nephrectomy and subsequent sunitinib treatment 
6) 
Karnofsky performance status <70% 
For patients in France Karnofsky performance status ≤70% 
7) 
National Cancer Institute (NCI) Common Terminology criteria for Adverse Events (CTCAE) 
Grade 3 hemorrhage within 28 days before Screening 
8) 
Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the 
normal range with medication 
9) 
Clinically significant gastrointestinal abnormalities 
10) 
Uncontrolled hypertension, or uncontrolled diabetes mellitus 
11) 
Pulmonary embolism within 12 months prior to Screening 
12) 
Prior history of invasive cancer within 5 years before Screening, except for adequately 
treated in situ carcinomas or non-melanoma skin cancer 
13) 
Ongoing infection that requires parenteral treatment with antibiotics 
14) 
Active or latent virus disease (HIV, HBV and HCV) 
15) 
ECOG performance status >2 after optimization of analgesics 
16) 
Abnormal or clinically significant coagulation parameters at the discretion of the investigator, i.e.: 
• 
Prothrombin Time - International Normalized Ratio (PT-INR) 
• 
Activated Partial Thromboplastin Time (APTT) 
Patients being treated with anticoagulants are excluded if the coagulation parameters are 
outside the therapeutic intervals as described in the SmPC/USPI for the administered 
treatment 
17) 
Known major adverse reaction/event in connection with previously made vaccination (e.g. 
asthma, anaphylaxis or other serious reaction) 
18) 
Known hypersensitivity or allergy to sunitinib or to chemically related products or likely to be 
exacerbated by any component of the study products 
19) 
Prior systemic antitumor therapy within 28 days before Screening Visit. However, local radiation 
therapy to any area except for the abdominal/retroperitoneal area including the kidney tumor is 
allowed  
20) 
Exposure to other investigational products within 28 days prior to Screening Visit 
21) 
Patients on anticoagulants for whom temporarily stop and start, supported by low molecular 
weight heparin (or other anticoagulation therapy at the discretion of the Investigator and/or per 
local standard of care) during vaccination and nephrectomy, is not an option 






Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 8 of 87 
2 
TABLE OF CONTENTS 
Section 
Page 
1 
SYNOPSIS ............................................................................................................... 2 
2 
TABLE OF CONTENTS ........................................................................................... 8 
3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .................................. 12 
3.1 
List of Abbreviations ................................................................................... 12 
3.2 
Definition of Terms...................................................................................... 15 
4 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE ....................... 17 
5 
INTRODUCTION .................................................................................................... 19 
5.1 
Background ................................................................................................. 19 
5.2 
Study Rationale ........................................................................................... 21 
5.3 
Potential Risks and Benefits ...................................................................... 21 
6 
STUDY OBJECTIVES ........................................................................................... 25 
6.1 
Primary Objectives ...................................................................................... 25 
6.2 
Secondary Objectives ................................................................................. 25 
6.3 
 ............................................................. 26 
7 
INVESTIGATIONAL PLAN .................................................................................... 27 
7.1 
Study Design and Plan-Description ........................................................... 27 
7.2 
Study Procedures ....................................................................................... 28 
7.2.1 
Schedule of Study Events ........................................................... 28 
7.2.1.1 
Screening Visit ............................................................................ 28 
7.2.1.2 
Vacc1 Visit (if applicable) ............................................................ 29 
7.2.1.3 
Vacc2 Visit (If applicable) ............................................................ 30 
7.2.1.4 
Nephrectomy Visit ....................................................................... 30 
7.2.1.5 
Sun-Start Visit ............................................................................. 31 
7.2.1.6 
SFU[6W], SFU[12W], SFU[24W], SFU[36W], SFU[48W], and 
SFU[60W] ................................................................................... 31 
7.2.1.7 
End of Study Visit ........................................................................ 32 
7.2.1.8 
Safety Evaluation 30 Days after Last Dose of Investigational 
Medicinal Product ....................................................................... 32 
7.2.1.9 
Extra Visits .................................................................................. 32 
7.2.1.10 
Post-Study Survival Information .................................................. 33 
7.2.2 
Study Flow Charts ....................................................................... 34 
7.3 
Discussion of Study Design, Including the Choice of Control Groups ... 38 
7.4 
Study Period ................................................................................................ 38 
7.5 
End of Study ................................................................................................ 38 
8 
SELECTION OF STUDY POPULATION ................................................................ 39 
8.1 
Number of Patients ..................................................................................... 39 
8.2 
Inclusion Criteria ......................................................................................... 39 
8.3 
Exclusion Criteria ........................................................................................ 40 
8.4 
Restrictions ................................................................................................. 41 
8.5 
Removal of Patients from Therapy or Assessment .................................. 41 
8.6 
Premature Termination of the Study .......................................................... 42 
8.7 
Study Stopping Criteria .............................................................................. 42 
9 
TREATMENT OF PATIENTS ................................................................................. 44 
9.1 
Investigational Medicinal Products ............................................................ 44 
9.1.1 
Treatment Regimens................................................................... 44 
9.1.2 
Identity of Investigational Medicinal Products .............................. 44 
9.1.3 
Packaging and Labelling of Investigational Medicinal Products ... 44 
9.1.4 
Storage, Handling and Dispensing of Investigational Medicinal 
Products...................................................................................... 45 
9.1.5 
Administration of Investigational Medicinal Products ................... 45 




Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 10 of 87 
11.1.4 
Serious Adverse Event ................................................................ 64 
11.2 Reporting of Adverse Events ..................................................................... 64 
11.3 Reporting of Serious Adverse Events ....................................................... 67 
11.4 SAE and SUSAR Reporting to CAs, IRBs/IECs, and Investigators .......... 68 
11.5 Dose Limiting Toxicity (DLT) ...................................................................... 68 
11.6 Precautions/Overdose ................................................................................ 69 
11.7 Pregnancy .................................................................................................... 69 
12 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE ................ 70 
12.1 Statistical and Analytical Plans .................................................................. 70 
12.1.1 
Data Sets to be Analyzed ............................................................ 70 
12.1.2 
Definitions ................................................................................... 70 
12.1.3 
Statistical Issues ......................................................................... 70 
12.1.4 
Summary Statistics ..................................................................... 70 
12.1.5 
Primary Efficacy Analyses ........................................................... 71 
12.1.6 
Secondary Efficacy Analyses ...................................................... 71 
12.1.7 
 .................................................. 72 
12.1.8 
Pharmacokinetic Analysis - N/A .................................................. 72 
12.1.9 
Demographic and Other Baseline Characteristics ....................... 73 
12.1.10 
Exposure to Treatment ................................................................ 73 
12.1.11 
Concomitant Treatment ............................................................... 73 
12.1.12 
Adverse Events ........................................................................... 73 
12.1.13 
Other Safety Assessments .......................................................... 73 
12.2 Determination of Sample Size .................................................................... 74 
12.3 Procedures for Reporting any Deviation(s) from the Original Statistical 
Analysis Plan ............................................................................................... 74 
12.4 Interim Analysis .......................................................................................... 74 
12.5 Follow-up Analysis of Post-Study Survival Data ...................................... 74 
13 
INVESTIGATOR/SPONSOR RESPONSIBILITIES ................................................ 75 
13.1 Ethics ........................................................................................................... 75 
13.1.1 
Institutional Review Boards/Independent Ethics Committees  and 
Competent Authorities ................................................................. 75 
13.1.2 
Ethical Conduct of the Study ....................................................... 75 
13.1.3 
Patient Information and Consent ................................................. 75 
13.2 Patient Records and Source Data .............................................................. 75 
13.3 Access to Source Data and Documentation.............................................. 76 
13.4 Monitoring ................................................................................................... 76 
13.5 Training of Study Personnel ....................................................................... 77 
13.6 Data Management ....................................................................................... 77 
13.7 Quality Assurance and Audit ..................................................................... 77 
13.8 Record Retention ........................................................................................ 77 
13.9 Protocol Deviations..................................................................................... 78 
13.10 Protocol Amendments ................................................................................ 78 
13.11 Insurance ..................................................................................................... 78 
13.12 Report and Publication ............................................................................... 78 
14 
REFERENCE LIST ................................................................................................ 80 
15 
SIGNATURES ........................................................................................................ 83 
16 
CLINICAL STUDY PROTOCOL AGREEMENT FORM.......................................... 85 
16.1 Clinical Study Protocol Agreement Form .................................................. 85 
17 
APPENDICES ........................................................................................................ 86 
Appendix A:  
 ................................................................... 86 
 
LIST OF TABLES 
Table 1 
Identified Risks and Risk Minimization Actions ................................................... 22 


Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 11 of 87 
Table 2 
Study Flow Chart ................................................................................................ 34 
Table 3 
Detailed Instructions on Assessments in Connection with Vaccination ............... 37 
Table 4 
Target Lesions Evaluation Criteria...................................................................... 53 
Table 5 
Non-Target Lesions Evaluation Criteria .............................................................. 53 
Table 6 
Evaluation of Best Overall Response ................................................................. 54 
Table 7 
Laboratory Safety Parameters (Blood) ............................................................... 62 
Table 8 
Laboratory Safety Parameters (Urine) ................................................................ 62 
 
LIST OF FIGURES 
Figure 1 
Overall Study Design.......................................................................................... 28 


Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 12 of 87 
3 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
3.1 
List of Abbreviations 
AB plasma 
Plasma from blood with blood-group AB 
AE 
Adverse Event 
ALAT 
Alanine Aminotransferase 
ALP 
Alkaline Phosphatase 
APTT 
Activated Partial Thromboplastin Time 
ASA 
Acetylsalicylic Acid 
ASAT 
Aspartate Aminotransferase 
BP 
Blood Pressure 
CA 
Competent Authority 
Ca 
Calcium 
CD 
Cluster of designation 
CFR 
Code of Federal Regulations 
CNS 
Central Nervous System 
CR 
Complete Response 
Creat 
Creatinine 
CT 
Computerized Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events  
DC 
Dendritic cell 
DCR 
Disease Control Rate 
DLT 
Dose Limiting Toxicity 
DMSO 
Dimethyl sulfoxide 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
EEA 
European Economic Area 
EORTC 
European Organisation for Research and Treatment of Cancer 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 
GFR 
Glomerular Filtration Rate 
GGT 
Gamma-Glutamyl Transferase 
Gluc 
Glucose 
Hb 
Hemoglobin 
HBV 
Hepatitis B Virus 


Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 13 of 87 
HCC 
Hepatocellular Carcinoma  
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
HLA 
Human Leukocyte Antigen 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IF-ANA 
Anti-nuclear antibodies 
IFN 
Interferon 
IL 
Interleukin 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
LLN 
Lower Limit of Normal 
LMWH 
Low Molecular Weight Heparin 
MHC 
Major Histocompatibility Complex 
MedDRA 
Medical Dictionary for Regulatory Activities 
mRCC 
Metastatic Renal Cell Carcinoma 
MRI 
Magnetic Resonance Imaging 
Na 
Sodium 
NCI 
National Cancer Institute 
ORR 
Objective Response Rate 
OS 
Overall Survival 
PD 
Progressive Disease 
PFS 
Progression Free Survival 
PPS 
Per Protocol Set 
PR 
Partial Response 
PT-INR 
Prothrombin Time - International Normalized Ratio 
 
 
 
 
RBC 
Red Blood Cells 
RCC 
Renal Cell Carcinoma 
RECIST 
Response Evaluation Criteria In Solid Tumors 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Stable disease 
SFU 
Sunitinib Follow-Up 
SmPC 
Summary of Product Characteristics 


Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 14 of 87 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
TKI  
Tyrosine Kinase Inhibitor 
TSH 
Thyroid-Stimulating Hormone 
TTF 
Time to Treatment Failure 
TTP 
Time to Progression 
ULN 
Upper Limit of Normal 
USPI 
United States Product Insert 
WBC 
White Blood Cell 
WHO 
World Health Organization 


Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 15 of 87 
3.2 
Definition of Terms 
NB: Detailed definitions of terms from the updated guideline Response Evaluation Criteria In 
Solid Tumors (RECIST v1.1) [1] are included in Section 10.2.2.2 and detailed definitions for 
Dose Limiting Toxicity (DLT) based on Common Terminology Criteria for Adverse Events 
(CTCAE) grading [2] for specific AEs are presented in Section 11.5. 
Baseline  
The date of randomization is defined as baseline for OS and 
18-month survival rate. 
The centrally assessed CT performed at the Sunitinib Start Visit is 
defined as CT baseline for evaluation of PFS, response rate and 
time to progression (TTP) after start of sunitinib in intermediate- and 
high-risk patients, Section 10.2.2.1, Section 10.2.2.2, and 
Section 10.2.2.3. Note: For intermediate-risk patients included in 
the trial according to protocol versions before version Final 4.0, 
baseline for PFS, ORR and duration of response, and TTP is 
defined as the first imaging assessment after nephrectomy. 
The Screening Visit is defined as baseline for all other assessments 
than those listed above. 
Competent Authority 
(CA) 
A government body or government appointed body that has legal 
authority to approve or disapprove clinical studies 
Eastern Cooperative 
Oncology Group 
(ECOG) criteria (also 
referred to as WHO 
or Zubrod) [3] 
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, e.g., light 
 
house work, 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 
High-risk mRCC 
patient according to 
Heng criteria [4] 
Patients fulfilling three (3) to six (6) of the following prognostic 
factors: 
• 
Hemoglobin (Hb) less than the lower limit of normal (LLN) 
• 
Corrected Calcium (Ca) greater than upper limit of normal 
(ULN) 
• 
Karnofsky performance status less than 80% 
• 
Time for diagnosis to treatment less than one (1) year 
• 
Neutrophils greater than ULN 
• 
Platelets greater than ULN 
Intermediate-risk 
mRCC patient 
One (1) or two (2) of the following prognostic factors: 
• 
Hb less than the lower limit of normal (LLN) 


Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 16 of 87 
according to Heng 
criteria [4] 
• 
Corrected Ca greater than upper limit of normal (ULN) 
• 
Karnofsky performance status less than 80% 
• 
Time for diagnosis to treatment less than one (1) year 
• 
Neutrophils greater than ULN 
• 
Platelets greater than ULN 
Karnofsky 
performance status 
[5] 
100% Normal; no complaints; no evidence of disease 
90% 
Able to carry on normal activity; minor signs or symptoms of 
 
disease 
80% 
Normal activity with effort; some signs or symptoms of 
 
disease 
70% 
Cares for self; unable to carry on normal activity or to do 
 
active  work 
60% 
Requires occasional assistance, but is able to care for most 
 
of his personal needs 
50% 
Requires considerable assistance and frequent medical 
 
care 
40% 
Disabled; requires special care and assistance 
30% 
Severely disabled; hospital admission is indicated although 
 
death not imminent 
20% 
Very sick; hospital admission necessary; active supportive 
 
treatment necessary 
10% 
Moribund; fatal processes progressing rapidly 
0% 
Dead 
 
 








Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 20 of 87 
excluded. The patients’ metastatic load varied. Five (5) patients were in the high-risk group 
and seven (7) in the intermediate group, according to the Heng prognostic model [4]. The 
Intuvax injections were performed with the patient hospitalized three (3) days to ensure safe 
care, collection of vital signs and blood samples. The vaccinations were performed twice, 
14 days apart, in all patients. Nephrectomy was performed two (2) weeks after the second 
vaccination. Three (3) different dose levels of DCs; 5 x106, 10 x106, and 20 x106, were 
administered. 
No serious adverse events (SAEs) related to the vaccination were noted. Transient fever 
reactions with duration less than one (1) day and rash was noted in 5 out of 12 patients. All 
patients survived the postoperative three (3) month follow-up visit. No significant deviations 
in blood chemistry attributable to the vaccination procedure were noted. Accidental bile duct 
injury was inflicted in one (1) patient resulting in transient hepatic failure. The renal function 
was decreased after nephrectomy in all patients as expected but no further decrease was 
observed except for one (1) patient who developed progressive renal function deterioration 
due to a previously undetected plasma cell disorder/myeloma. There were no signs of any 
autoimmune reactions as measured by standard tests while a humoral donor-specific 
alloimmunization was seen in three (3) patients. 
An increased number of tumor-specific lymphocytes were seen after vaccination in nine (9) 
patients indicating a systemic immune response. A dense infiltration of CD8+ T-cells was 
found in seven (7) nephrectomy specimens. Nephrectomy specimens with dense 
intratumoral T-cell infiltration exhibited only few and scattered CD8+ T-cells within the 
surrounding normal kidney parenchyma. These findings, together with the fact that the 
remaining renal function was not decreased more than anticipated, indicate that the 
observed cellular immune response was tumor specific and not directed towards normal 
renal structures. No correlation between Intuvax dose and intratumoral lymphocyte infiltration 
was observed. The degree of HLA-mismatch between vaccine-DCs and the patient was not 
correlating with degree of intratumoral CD8+ T-cell infiltration in this study. 
The selected patient population had primary mRCC and consequently they can be 
considered as a poor prognostic group per se. In addition, unfavorable histology with 
sarcomatoid differentiation was more common than anticipated prior to study start; six (6) 
tumors presented sarcomatoid differentiation. Four (4) of these exhibited an extensive 
sarcomatoid differentiation (>20% of the tumor tissue), reflecting a highly unfavorable clinical 
presentation. All patients have progressed after nephrectomy and six (6) patients have 
received additional treatment with TKIs. The median OS in the subgroup of five (5) patients 
with high-risk/poor prognosis according to Heng criteria, of which four (4) patients have 
received additional TKI treatment, was 24.5 months. Additional treatments with surgery and 
radiotherapy have been given after progression to some patients. 
In conclusion, the observed intratumoral infiltration of potentially cytotoxic CD8+ T-cells merit 
further studies in order to correlate this finding with clinical outcome. No correlation of DC 
dose and the immune response in the kidney could be identified. Circulating vaccine-DCs 
were transiently found in a minority of patients and usually in low numbers. 
Fully mature allogeneic DCs have previously been tested in approximately 100 RCC patients 
using different administration routes [9,10,11,12,13]. These studies provide additional 
supporting safety information of the use of allogenic DC-based vaccines in treatment of RCC. 
Only mild AEs have been reported and no SAEs have been observed. The most commonly 
reported AEs in those studies were local reactions at the administration site (rash) and fever. 
No signs of autoimmunity have been observed. 
 










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Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
Confidential 
Page 25 of 87 
6 
STUDY OBJECTIVES 
6.1 
Primary Objectives 
The primary objectives are: 
• 
To evaluate median OS from randomization in mRCC patients overall and by 
subgroup, i.e. in high-risk and in intermediate-risk patients separately, receiving two 
(2) vaccine doses of Intuvax pre-nephrectomy, followed by sunitinib initiated five (5) to 
eight (8) weeks post-nephrectomy and in non-vaccinated mRCC patients receiving 
sunitinib initiated five (5) to eight (8) weeks post-nephrectomy 
• 
To evaluate 18-month survival rate from randomization in mRCC patients overall and 
by subgroup, i.e. in high-risk and in intermediate-risk patients separately, receiving 
two (2) vaccine doses of Intuvax pre-nephrectomy followed by sunitinib post-
nephrectomy and in non-vaccinated patients receiving sunitinib post-nephrectomy 
6.2 
Secondary Objectives 
The secondary objectives are: 
• 
To evaluate safety and tolerability in high- and intermediate-risk mRCC patients 
receiving two (2) vaccine doses of Intuvax pre-nephrectomy followed by sunitinib 
post-nephrectomy and in non-vaccinated patients receiving sunitinib 
post-nephrectomy 
• 
To evaluate PFS according to Response Evaluation Criteria In Solid Tumors 
(RECIST) 1.1 criteria from Sunitinib Start Visit in intermediate- and high-risk mRCC 
patients after receiving two (2) vaccine doses of Intuvax pre-nephrectomy followed by 
sunitinib post-nephrectomy and in non-vaccinated patients receiving sunitinib 
post-nephrectomy* 
• 
To evaluate response and its duration according to RECIST 1.1 criteria from Sunitinib 
Start Visit in intermediate- and high-risk mRCC patients receiving two (2) vaccine 
doses of Intuvax pre-nephrectomy followed by sunitinib post-nephrectomy and in non-
vaccinated patients receiving sunitinib post-nephrectomy* 
• 
To evaluate time to progression (TTP) from Sunitinib Start Visit in intermediate- and 
high-risk mRCC patients receiving two (2) vaccine doses of Intuvax pre-nephrectomy 
followed by sunitinib post-nephrectomy and in non-vaccinated patients receiving 
sunitinib post-nephrectomy* 
• 
To evaluate the number of infiltrating CD8+ T-cells in available diagnostic pre-biopsy 
(sample from either primary tumor or metastasis acceptable) and in the resected 
primary renal tumor in intermediate- and high-risk mRCC patients receiving two (2) 
vaccine doses of Intuvax pre-nephrectomy and in non-vaccinated patients 
*Note: For intermediate-risk patients included in the trial according to protocol versions 
before version Final 4.0, baseline for PFS, ORR response and its duration, and TTP is 
defined as the first imaging assessment after nephrectomy. 
 




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Study Code: IM-201 
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EudraCT No.: 2014-004510-28 
Confidential 
Page 27 of 87 
7 
INVESTIGATIONAL PLAN 
7.1 
Study Design and Plan-Description 
The study is an open-label, randomized, controlled, two (2) armed, multicenter, phase II 
study. Intermediate- and high-risk mRCC patients according to Heng criteria are eligible for 
participation [4]. Stratified randomization based on Heng-risk categories applies. The patients 
are randomized in a consecutive order to one (1) of the following two (2) treatment arms 
when eligibility has been confirmed; 
(i) 
Two (2) doses of Intuvax (10x106 DCs) administered intratumorally into the 
primary tumor 14 ±3 days apart followed by nephrectomy at least three (3) 
days after the second vaccine dose.  
AND 
Sunitinib treatment initiated five (5) to eight (8) weeks after nephrectomy, 
administered dose in accordance with the SmPC/USPI. 
(ii) 
Sunitinib treatment initiated five (5) to eight (8) weeks after nephrectomy, 
administered dose in accordance with the SmPC/USPI. 
The estimated number of patients to be randomized in the study is around 90. The patients 
will be randomized in a 2:1 (vaccine treatment arm [i]:control treatment arm [ii]) ratio. 
Stratification will be done at randomization for intermediate- and high-risk patients. 
Patients randomized to treatment arm (i) are scheduled for 12 study visits and patients 
randomized to treatment arm (ii) are scheduled for 10 study visits during a study period of 
78 weeks, see list below and Figure 1. In addition, all patients being exposed to any of the 
Investigational Medicinal Products (IMPs) will have a safety evaluation done for collection of 
SAEs up to 30 days after last dose of IMP administered in the study. The following visits 
apply for the two (2) patient populations: 
• 
Screening Visit (Screening) 
• 
Vaccination 1 Visit (Vacc1), applicable for patients randomized to treatment arm (i) 
• 
Vaccination 2 Visit (Vacc2), applicable for patients randomized to treatment arm (i) 
• 
Nephrectomy Visit (Nephrectomy) 
• 
Sunitinib Start Visit (Sun-Start), five (5) to eight (8) weeks after Nephrectomy  
• 
Sunitinib Follow-up Visits (SFU[6W] and SFU[12W]), every 6 weeks for 12 weeks or 
until locally CT-verified PD whichever occurs first  
• 
Sunitinib Follow-up Visits (SFU[24W], SFU[36W], SFU[48W], and SFU[60W]), every 
12 weeks until End-of study or until locally CT-verified PD whichever occurs first  
• 
End-of-Study Visit (End-of-Study) 
At the two (2) Vaccination Visits, the patients will be administered Intuvax (10 x106 DCs) 
intratumorally in the viable part of their primary tumor. Vaccine from the same batch (i.e. the 
same donor) will be used at both occasions. The patient will stay at the clinic at least 
four (4) hours after vaccination. Nephrectomy is done at least 3 days after the second 
vaccination and maximum 63 days after Screening. Sunitinib treatment is initiated five (5) to 
eight (8) weeks after nephrectomy, administered dose is in accordance with the SmPC/USPI. 
All patients will be encouraged to contact the clinic in between study visits if they experience 
adverse events (AEs) or have any concerns. If follow-up of any symptoms is needed 




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Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
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Page 29 of 87 
• 
Vital Signs, Section 10.5.4 
• 
ECG, Section 10.4.5 
• 
Laboratory Safety Blood Assessments: Hematology, Clinical Chemistry including 
Glomerular Filtration Rate (GFR) based on Creatinine (Creat), Glucose (Gluc), 
Thyroid stimulating hormone (TSH), Thyroxine (free T4), and Prothrombin Time - 
International Normalized Ratio (PT-INR), Activated Partial Thromboplastin Time 
(APTT), and Pregnancy Section 10.5.5 
• 
Laboratory Safety Urine Assessments, Section 10.5.5 
• 
Additional Laboratory Blood Assessments: Serology (HIV, HBV, and HCV), 
Section 10.4.6, High resolution tissue typing of Human Leukocyte Antigens (HLA), 
Section 10.4.7 
• 
ECOG score, Section 10.2.3.1 and Karnofsky performance status, Section 3.2 
• 
 Section 10.2.3.2 
• 
Inclusion/Exclusion Criteria, Section 8.2 and Section 8.3. To be checked when the 
results from all assessments made at Screening are available. 
• 
Randomization, Section 9.2. To be done when eligibility has been confirmed. 
• 
Confirmatory diagnostic biopsy in accordance with local routines prior to Vacc1 Visit, 
if required by local regulations and laws, Section 9.2. 
• 
AEs, Section 11.2 
A telephone contact will be made with the patient once randomization has been done in 
order to inform about which treatment the patient was allocated to and for scheduling the 
next study visit and a confirmatory biopsy if applicable. 
Extra consent for vaccination for patients randomized to the vaccine arm, to be taken after 
randomization if required by local regulations. 
 
7.2.1.2 Vacc1 Visit (if applicable) 
This visit is applicable only for patients randomized to Intuvax followed by sunitinib. 
TIME WINDOW: 
Vacc1 Visit to be done within 28 days after Screening 
ACTIVITIES AND ASSESSMENTS: 
Day before vaccination (optional): 
The following assessments may be done the day before vaccination for logistical reasons: 
• 
Laboratory Safety Blood Assessments: Hematology, Clinical Chemistry, PT-INR, and 
APTT, Section 10.5.5 
• 
Pregnancy (either blood or urine), Section 10.5.5 
• 
Laboratory Safety Urine Assessments, Section 10.5.5 
• 
Physical Examination, Section 10.5.3 
• 
ECOG performance status, Section 10.2.3.1 
• 
AEs, Section 11.2 
Day of vaccination (Pre-Vaccination): 


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Page 30 of 87 
NB: Absolute fasting for four (4) h prior to Intuvax administration applies. 
• 
Concomitant Medication, Section 10.4.4 
• 
Physical Examination unless done the day before, Section 10.5.3 
• 
Vital Signs, Section 10.5.4 
• 
Laboratory Safety Blood Assessments: Hematology, Clinical Chemistry, PT-INR, and 
APTT unless done the day before, Section 10.5.5 
• 
Pregnancy (either blood or urine test) unless done the day before, Section 10.5.5 
• 
Laboratory Safety Urine Assessments unless done the day before, Section 10.5.5 
• 
Auto- and alloimmunization (baseline), Section 10.5.6.1 and Section 10.5.6.2 
• 
ECOG performance status unless done the day before, Section 10.2.3.1 
• 
AEs, Section 11.2 
Day of vaccination (Vaccination) 
• 
Injection of Intuvax into the viable part of the renal tumor using CT or Ultrasound 
monitoring for confirmation of administration location, Section 9.1.5 
Day of vaccination (Post-Vaccination) 
• 
Vital Signs, Section 10.5.4 
• 
AEs, Section 11.2 
• 
Concomitant Medication, Section 10.4.4 
 
7.2.1.3 Vacc2 Visit (If applicable) 
This visit is applicable only for patients randomized to Intuvax followed by sunitinib. 
TIME WINDOW: 
14 days (±3 days) after Vacc1 Visit 
ACTIVITIES AND ASSESSMENTS 
Exactly the same activities and assessments will be done at this visit as was done on Vacc1 
Visit except for auto- and alloimmunization, Section 7.2.1.2. 
 
7.2.1.4 Nephrectomy Visit  
This visit is applicable for all patients. 
TIME WINDOWS: 
At least 3 days after Vacc2 Visit and within 63 days from Screening Visit for patients 
randomized to Intuvax followed by sunitinib. 
Within 63 days from Screening Visit for patients randomized to sunitinib only. 
ACTIVITIES AND ASSESSMENTS: 
Prior to Nephrectomy (may be done the day before vaccination for logistical reasons) 
• 
Concomitant Medication, Section 10.4.4 
• 
Laboratory Safety Blood Assessments:All patients: Hematology and Clinical 
Chemistry, for patients on anticoagulants: also PT-INR, and APTT, Section 10.5.5 


Clinical Study Protocol 
Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
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Page 31 of 87 
• 
Laboratory Safety Urine Assessments, Section 10.5.5 
• 
, Section 10.2.3.2 
• 
AEs, Section 11.2 
Nephrectomy and post Nephrectomy assessments 
• 
Nephrectomy, Section 9.1.1 
• 
Biopsies for central assessments of infiltrating CD8+ T-cells and immunohistology, 
Section 10.2.2.4 and Section 10.2.3.3. 
• 
AEs, Section 11.2 
• 
Confirmation of mRCC diagnosis, Section 10.4.2 
 
7.2.1.5 Sun-Start Visit  
This visit is applicable for all patients.  
TIME WINDOW: 
Five (5) to eight (8) weeks after Nephrectomy Visit 
NB: The CT scan does not have to be done the very same day as the study visit. However, it 
has to be done within the above specified time window. 
The laboratory safety blood and urine assessments do not have to be done the very same 
day as the study visit. However, it has to be done a maximum of 3 days prior to the visit. 
ACTIVITIES AND ASSESSMENTS: 
• 
CT Scan, Section 10.4.3 including specification of target lesions Section 10.2.2.2  
• 
Concomitant Medication, Section 10.4.4 
• 
Physical Examination, Section 10.5.3 
• 
Vital Signs, Section 10.5.4 
• 
Laboratory Safety Blood Assessments: Hematology and Clinical Chemistry including 
GFR based on Creat, Gluc, TSH, and Thyroxine [free T4], Section 10.5.5 
• 
Laboratory Safety Urine Assessments, Section 10.5.5 
• 
Auto- and alloimmunization (only for patients treated with Intuvax), Section 10.5.6.1 
and Section 10.5.6.2 
• 
ECOG performance status, Section 10.2.3.1 
• 
 Section 10.2.3.2 
• 
Start of sunitinib treatment. Dispense of sunitinib, Section 9.1.4 
• 
AEs, Section 11.2 
 
7.2.1.6 SFU[6W], SFU[12W], SFU[24W], SFU[36W], SFU[48W], and SFU[60W] 
These visits are applicable for all patients unless locally CT-verified PD occurs. In case of PD 
this visit should be considered the End-of-Study Visit. 
If SFU[60W] is scheduled ≥76 weeks since Screening this visit should be considered the 
End-of-Study Visit, Section 7.2.1.7. 


Clinical Study Protocol 
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TIME WINDOWS: 
SFU[6W]: 
  6 weeks (±7 days) after Sun-Start Visit 
SFU[12W]: 12 weeks (±7 days) after Sun-Start Visit 
SFU[24W]: 24 weeks (±7 days) after Sun-Start Visit 
SFU[36W]: 36 weeks (±7 days) after Sun-Start Visit 
SFU[48W]: 48 weeks (±7 days) after Sun-Start Visit 
SFU[60W]: 60 weeks (±7 days) after Sun-Start Visit 
NB: The CT/MRI scans do not have to be done the very same day as the corresponding 
study visits. However, each CT/MRI scan has to be done within the specified time window for 
the corresponding visit. 
ACTIVITIES AND ASSESSMENTS: 
The same activities and assessments will be done at these visits as was done on Sun-Start 
Visit except for auto- and alloimmunization, Section 7.2.1.5. In addition to dispense of 
sunitinib, the site personnel will collect unused and empty sunitinib packages (distributed at 
the previous visit) from the patient for drug accountability, Section 9.1.4. 
 
7.2.1.7 End of Study Visit  
This visit is applicable for all patients. 
TIME WINDOW: 
78 ±2 weeks after Screening 
NB: The CT/MRI scan does not have to be done the very same day as the study visit. 
However, it has to be done within the above specified time window. 
ACTIVITIES AND ASSESSMENTS: 
The same activities and assessments will be done at this visit as was done on SFU[6W] to 
SFU[60W] Visits, Section 7.2.1.6. No dispense of sunitinib will be done. 
 
7.2.1.8 Safety Evaluation 30 Days after Last Dose of Investigational Medicinal Product 
The safety evaluation, i.e. collection of SAEs, as described in Section 11.2 is applicable for 
all patients who have received any IMP. 
ACTIVITIES AND ASSESSMENTS: 
• 
SAEs, Section 11.2 
 
7.2.1.9 Extra Visits  
Extra Visits are applicable for all patients if any symptoms need follow-up between planned 
visits. 
TIMING: 
The patient will be scheduled for a visit as soon as possible. 
ACTIVITIES AND ASSESSMENTS: 
• 
Concomitant Medication, Section 10.4.4 
• 
Physical Examination, Section 10.5.3 
• 
Vital Signs, Section 10.5.4 


Clinical Study Protocol 
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Study Code: IM-201 
Date: 12 February 2019 
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Page 33 of 87 
• 
Laboratory Safety Blood Assessments: Hematology and Clinical Chemistry. If the 
Extra Visit is scheduled after the Sun-Start Visit the assessments will also include 
GFR based on Creat, Gluc, TSH, and Thyroxine [free T4], Section 10.5.5 
• 
Laboratory Safety Urine Assessments, Section 10.5.5 
• 
ECOG performance status, Section 10.2.3.1 
• 
AEs, Section 11.2 
• 
Additional laboratory tests and other assessments as applicable to the discretion of 
the Investigator 
 
7.2.1.10 Post-Study Survival Information 
This measure is applicable for all patients.  
• 
Survival data, Section 11.3  


Clinical Study Protocol 
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Study Code: IM-201 
Date: 12 February 2019 
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7.2.2 Study Flow Charts 
Detailed instructions on vital signs, AE collection, and blood sampling in connection to vaccination are shown in Table 3. 
Table 2 
Study Flow Chart  
Visit  
Screening 
 
 
Day 1 
Vacc1 
Intuvax + 
sunitinib: 
 
Day 2-28 
sunitinib 
only: 
 
N/A 
Vacc2 
Intuvax + 
sunitinib: 
 
Day 16-42 
sunitinib 
only: 
 
N/A 
Nephrectomy 
Intuvax + 
sunitinib: 
 
Day 19-63 
sunitinib  
only: 
 
Day 63 at the 
latest 
Sun-Start 
5 to 8 weeks  
after Nephr.j 
 
SFU[6W] 
6w ±7d  
after Sun-Start 
SFU[12W] 
12w ±7d  
after Sun-Start 
SFU[24W] 
24w ±7d  
after Sun-Start 
SFU[36W] 
36w ±7d  
after Sun-Start 
SFU[48W] 
48w ±7d  
after Sun-Start 
SFU[60W]o 
60w ±7d  
after Sun-Start 
End-of- 
Study 
78w ±2w  
after Screening 
Safety 
Evaluation 
Collection of SAEs 
up to 30 days after 
last dose of IMP 
Extra visit 
 
 
When 
needed 
Informed consent 
X 
Xs 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
Medical and Surgical History 
X 
 
 
 
 
 
 
 
 
CT/MRI scanl 
Xm 
 
 
 
Xt 
Xt 
Xt 
 
 
Prior and/or Concomitant 
Medication 
X 
X 
X 
Xa 
X 
X 
X 
 
X 
Physical Examination 
X 
X 
X 
 
X 
X 
X 
 
X 
Vital Signsb 
X 
Xc 
Xc 
 
X 
X 
X 
 
X 
ECG 
X 
 
 
 
 
 
 
 
 
Hematology and Clin. Chem. 
X 
Xd 
Xd 
Xa,d 
Xu 
X 
X 
 
X 
GFR based on Creat, Gluc, 
TSH, and Thyroxine (free T4) 
X 
 
 
 
X 
X 
X 
 
Xn 
PT-INR 
X 
Xd 
Xd 
Xa,d 
 
 
 
 
 
APTT 
X 
Xd 
Xd 
Xa,d 
 
 
 
 
 
Pregnancy 
Xe 
Xe 
Xe 
 
 
 
 
 
 
Urinalyses 
X 
Xd 
Xd 
Xa 
Xu 
X 
X 
 
X 
HIV/HBV/HCV and HLA  
X 
 
 
 
 
 
 
 
 


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Cont. Table 2  Study Flow Chart 
Visit  
Screening 
 
 
Day 1 
Vacc1 
Intuvax + 
sunitinib: 
 
Day 2-28 
sunitinib 
only: 
 
N/A 
Vacc2 
Intuvax + 
sunitinib: 
 
Day 16-42 
sunitinib 
only: 
 
N/A 
Nephrectomy 
Intuvax + 
sunitinib: 
 
Day 19-63 
sunitinib  
only: 
 
Day 63 at the 
latest 
Sun-Start 
5 to 8 weeks  
after Nephr.j 
 
SFU[6W] 
6w ±7d  
after Sun-Start 
SFU[12W] 
12w ±7d  
after Sun-Start 
SFU[24W] 
24w ±7d  
after Sun-Start 
SFU[36W] 
36w ±7d  
after Sun-Start 
SFU[48W] 
48w ±7d  
after Sun-Start 
SFU[60W]o 
60w ±7d  
after Sun-Start 
End-of- 
Study 
78w ±2w  
after Screening 
Safety 
Evaluation 
Collection of SAEs 
up to 30 days after 
last dose of IMP 
Extra visit 
 
 
When 
needed 
Auto- and Alloimmunization 
 
Xf 
 
 
Xf 
 
 
 
 
ECOG performance  
X 
Xd 
Xd 
 
X 
X 
X 
 
X 
Karnofsky performance  
X 
 
 
 
 
 
 
 
 
 
X 
 
 
Xa 
X 
X 
X 
 
 
Inclusion/Exclusion criteria 
Xg 
 
 
 
 
 
 
 
 
Randomization 
Xg 
 
 
 
 
 
 
 
 
Confirmatory diagnostic 
biopsy 
Xp 
 
 
 
 
 
 
 
 
Nephrectomy 
 
 
 
X 
 
 
 
 
 
Biopsies (tumor x2, adjacent 
normal tissue)  
 
 
 
X 
 
 
 
 
 
Administration of Intuvaxq  
 
Xc 
Xc 
 
 
 
 
 
 
Sunitinib dispense & returnh 
 
 
 
 
Xi 
X 
Xi 
 
 
AEs 
X 
Xc 
Xc 
X 
X 
X 
Xk 
Xv 
X 
Diagnosis Confirmationr 
 
 
 
X 
 
 
 
 
 
a Assessment to be completed before nephrectomy and may be done the day before nephrectomy for logistical reasons 
 
Locally analyzed Creatinine for patients included in the study before 28 August 2017 (if performed as part of clinical routine) to be recorded in eCRF 
b Height only at Screening. Weight at all visits except for Vacc1 and Vacc2 Visits. 
c See specific flow chart, Table 3, for detailed instructions on pre- and post-vaccination assessments. 
d Physical examination, ECOG performance, and samples for safety lab and urinalyses may be taken the day before vaccination for logistical reasons 
 
Locally analyzed results for Hb, WBC, platelets, PT-INR, and APTT need to be available before vaccination 
 
Locally analyzed results for Hb, WBC, and clinical chemistry might need to be available prior to nephrectomy 


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Analysis of coagulation status at Nephrectomy is not necessary provided the patient is not on anticoagulant treatment. For patients on anticoagulants local sampling practice 
applies. 
e Pregnancy test in blood at Screening, and in either blood or urine at Vacc1 and Vacc2 Visits. The pregnancy test result is needed prior to each vaccination. 
f 
Samples for auto- and alloimmunization analyses will be collected prior to vaccination at Vacc1 Visit. Sampling at Sun-Start Visit only applicable for patients randomized to 
Intuvax.  
g To be done when the results from all assessments made are available. Telephone contact with patient to inform about treatment and timing of next study visit. 
h The prescribed dose to be in accordance with the SmPC/USPI including any dose adjustments.  
i 
Return of sunitinib not applicable at Sun-Start Visit and Distribution not applicable at End-of-Study Visit. Standard of Care applies after End-of-Study. 
j 
Start of sunitinib administration will be dependent on wound healing. The time window for initiation is five (5) to eight (8) weeks after Nephrectomy. 
k Post-study collection of survival data. 
l 
If CT cannot be used for some reason, MRI is acceptable. The same modality has to be used at all visits. 
m CT scan to be done within 3 weeks before Screening unless a CT scan has been done in clinical routine within 6 weeks before Screening. Brain imaging (preferably by 
contrast-enhanced) MRI or CT to be done within 3 weeks before Screening Visit unless a CT scan has been performed in clinical routine within 6 weeks prior to Screening 
Visit 
n  To be done if Extra Visit is scheduled after Sun-Start Visit 
o If SFU[60W] is scheduled ≥76 weeks since Screening this visit should be considered the End-of-Study Visit 
p Confirmatory diagnostic biopsy in accordance with local routines prior to Vacc1 Visit, if required by local regulations and laws 
q Absolute fasting for four (4) h prior to Intuvax administration applies 
r 
Routine histology/Primary diagnosis is assessed locally 
s Extra consent for vaccination for patients randomized to the vaccine arm, to be taken after randomization if required by local regulations 
t 
The CT scan does not have to be done the very same day as the corresponding study visit. However, each CT scan has to be done within the specified time window for the 
 
corresponding visit 
u The laboratory safety blood and urine assessments do not have to be done the very same day as the study visit. However, it has to be done within 3 days prior to the visit. 
v SAEs only to be recorded and reported, see Section 11.2 
 
 
 
 
 


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Table 3 
Detailed Instructions on Assessments in Connection with Vaccination 
Assessment 
Pre-
vaccination 
Vaccination  
Post-vaccination  
> 2 h  
0 h 
 
 15 min 
(±5 min) 
30 min 
(±10 min) 
60 min  
(±10 min) 
2 h  
(±10 min) 
3 h  
(±10 min) 
4 h 
(±20 min) 
Intuvax injection  
 
X 
 
 
 
 
 
 
BP 
X 
 
X 
X 
X 
X 
X 
X 
HR 
X 
 
X 
X 
X 
X 
X 
X 
Body temperature 
X 
 
 
X 
X 
X 
X 
X 
AEs 
X 
 
X 
X 
X 
X 
X 
X 


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7.3 
Discussion of Study Design, Including the Choice of Control Groups 
Intuvax is developed as an immune primer for cancer treatment that preferably should be 
combined with a drug that acts in synergy with Intuvax by inhibiting tumor-induced 
immunosuppression. In this study, Intuvax is given in combination with sunitinib, which like 
several other TKIs is known to inhibit myeloid-derived suppressor cells [25]. Based on 
current ESMO and NCCN guidelines [26, 27, 28] today’s standard of care both in US and in 
the majority of the European countries involves initiation of systemic treatment with a TKI 
(including sunitinib or pazopanib) approximately 6 weeks post nephrectomy for all patients 
regardless of prognosis, i.e. poor (high risk) or intermediate. It is anticipated that all patients 
will benefit more from vaccination with Intuvax the sooner TKI treatment is initiated after 
performed nephrectomy.  
Sunitinib alone was chosen as the active control for the study based on its documented 
positive impact on tumor response, PFS and OS in patients with mRCC. As discussed in 
Section 5.2 it is hypothesized that sunitinib might contribute to an increased Intuvax efficacy. 
 
7.4 
Study Period 
Expected timelines in the study: 
Start of inclusion: Q2 2015 
Planned last patient last study visit or last patient’s safety evaluation (up to 30 days after the 
last patient’s last dose of an IMP), whichever occurs later: Q3 2019 
 
7.5 
End of Study 
The end of study is defined as the last patient last visit (LPLV) or the last patient’s safety 
evaluation (up to 30 days after the last patient’s last dose of an IMP), whichever occurs later. 


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8 
SELECTION OF STUDY POPULATION 
8.1 
Number of Patients 
The estimated number of patients to be randomized in the study is around 90. The patients 
will be randomized in a 2:1 (vaccination:control) ratio. Stratification will be done at 
randomization for intermediate- and high-risk patients, Section 3.2, and Section 9.2.  
The choice of sample size is discussed in Section 12.2.  
The study will be performed at approximately 25 sites in EU and approximately 5 sites in US. 
Competitive recruitment will apply. 
 
8.2 
Inclusion Criteria 
The patients have to meet all of the following criteria to be eligible to enter the study: 
1)  Newly (<6 months) diagnosed RCC (histological/cytological verification is optional) with 
at least one (1) CT-verified metastasis ≥10 mm for which complete metastasectomy is 
not planned. US patients must have verified clear-cell tumor histology 
2) 
Planned resection of primary tumor 
3) 
Primary tumor diameter ≥40 mm 
4) 
Candidate for first-line therapy with Sunitinib initiated five (5) to eight (8) weeks after 
nephrectomy 
5) 
Female or male ≥18 years of age 
6) 
Willing and able to provide informed consent 
7) 
Adequate hematological parameters, i.e.: 
• 
B-Leukocyte count ≥4.5 x109/L 
• 
B-Platelet count ≥150 x109/L 
• 
B-Hemoglobin (Hb ≥90 g/L 
8) 
Serum-creatinine and serum-bilirubin ≤1.5 × ULN. Serum-ALAT and serum-ASAT 
≤2.5 × ULN (or ≤5 in case of liver metastases) 
9) 
Female who has been post-menopausal for more than one (1) year or female of 
childbearing potential agreeing to use a highly efficient method of contraception (i.e. a 
method with less than 1% failure rate [e.g. sterilization, hormone implants, hormone 
injections, some intrauterine devices, or vasectomized partner or combined birth 
control pills]) from Screening until 90 days after last dose of Intuvax and/or until 
completed sunitinib treatment whichever occurs later. Female of childbearing potential 
must have a negative blood pregnancy test at Screening, and if randomized to 
vaccination a negative blood or urine pregnancy test within one (1) day before each 
dose of Intuvax) and must not be lactating. 
 
or 
 
Male agreeing to use condoms from Screening until 90 days after last dose of Intuvax 
and/or until completed sunitinib treatment whichever occurs later, or male having a 
female partner who is using a highly efficient method of contraception as described 
above. 


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8.3 
Exclusion Criteria 
Patients meeting any of the following criteria will not be permitted to enter the study:  
1)  Life expectancy less than 4 months 
2) 
CNS metastasis that is symptomatic or progressing or untreated or that required 
current therapy (e.g. evidence of new or enlarging CNS metastasis or new neurological 
symptoms attributable to CNS metastases) 
3) 
Active autoimmune disease which requires treatment with systemic 
immunosuppressive agents, e.g. inflammatory bowel disease, multiple sclerosis, 
sarcoidosis, psoriasis, autoimmune hemolytic anemia, rheumatoid arthritis, SLE, 
vasculitis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, and other 
rheumatological diseases 
4) 
Treatment with per oral systemic corticosteroids exceeding 10 mg/day within 7 days 
before Screening until Nephrectomy (inhaled, intranasal and local steroids acceptable 
irrespective of dose) 
5) 
Known cardiomyopathy and/or clinically significant abnormal ECG findings at 
Screening disqualifying the patient from nephrectomy and subsequent sunitinib 
treatment 
6)  Karnofsky performance status <70%, Section 3.2 
For patients in France Karnofsky performance status ≤70%, Section 3.2 
7) 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 
(CTCAE) Grade 3 hemorrhage within 28 days before Screening 
8) 
Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the 
normal range with medication 
9)  Clinically significant gastrointestinal abnormalities 
10)  Uncontrolled hypertension or uncontrolled diabetes mellitus 
11)  Pulmonary embolism within 12 months prior to Screening 
12) 
Prior history of invasive cancer within 5 years before Screening, except for adequately 
treated in situ carcinomas or non-melanoma skin cancer 
13)  Ongoing infection that requires parenteral treatment with antibiotics 
14)  Active or latent virus disease (HIV, HBV and HCV) 
15)  ECOG performance status >2 after optimization of analgesics, Section 3.2 
16) 
Abnormal or clinically significant coagulation parameters at the discretion of the 
investigator, i.e.: 
- 
Prothrombin Time - International Normalized Ratio (PT-INR) 
- 
Activated Partial Thromboplastin Time (APTT) 
Patients being treated with anticoagulants are excluded if the coagulation parameters 
are outside the therapeutic intervals as described in the SmPC/USPI for the 
administered treatment 
17) 
Known major adverse reaction/event in connection with previously made vaccination 
(e.g. asthma, anaphylaxis or other serious reaction) 
18) 
Known hypersensitivity or allergy to sunitinib or to chemically related products or likely 
to be exacerbated by any component of the study products 


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19) 
Prior systemic antitumor therapy within 28 days before Screening Visit. However, local 
radiation therapy to any area except for the abdominal/retroperitoneal area including 
the kidney tumor is allowed  
20)  Exposure to other investigational products within 28 days prior to Screening Visit 
21) 
Patients on anticoagulants for whom temporarily stop and start, supported by low 
molecular weight heparin (or other anticoagulation therapy at the discretion of the 
Investigator and/or per local standard of care) during vaccination and nephrectomy, is 
not an option 
22)  History of alcohol or substance abuse 
23) 
Any reason that, in the opinion of the Investigator, contraindicates that the patient 
participates in the study 
8.4 
Restrictions  
Intuvax: 
Treatment requires absolute fasting for a period of 4 hours prior to  
 
 
vaccination. 
Sunitinib:  
Restrictions for treatment as in the SmPC/USPI for Sutent® (sunitinib), e.g. 
 
 
avoid concomitant administration of potent CYP3A4 inducers or inhibitors. 
Nephrectomy: Same restrictions apply as in clinical routine. 
 
8.5 
Removal of Patients from Therapy or Assessment 
Patients are free to discontinue their participation in the study at any time. Withdrawal from 
the study will not affect or prejudice the patient’s further care or treatment. Patients may be 
withdrawn from study treatment and assessments at any time, if deemed necessary by the 
Investigator. 
Patients who discontinue treatment with Intuvax and/or sunitinib for safety reasons (including 
DLT, see Section 11.5) or due to concomitant medication (Section 9.6) will not necessarily be 
considered withdrawn from the study unless there are other reasons for withdrawal. They 
should return for all following visits and assessments until PD. 
Examples of reasons for withdrawal of patients from this study are:  
• 
Progressive disease on sunitinib treatment 
• 
Screening failure 
• 
The decision of a patient to withdraw from the study (i.e. if the patient withdraws 
informed consent) 
• 
Administration of concomitant medication prohibited by this protocol, Section 9.6 
• 
Pregnancy 
• 
Patient is lost to follow-up 
• 
RCC diagnosis is not confirmed by histological findings from the biopsy collected at 
nephrectomy or, if applicable, from confirmatory pre-study treatment diagnostic 
biopsy 
The reason and date the patient is withdrawn from the study and subsequent planned 
replacement therapy will be documented in the electronic case report form (eCRF).  


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All patients that have received IMP must have safety evaluations for 30 days after the last 
dose of IMP, Section 11.2. 
If a patient is withdrawn from further assessments, the Investigator should attempt to 
complete all discharge procedures, i.e. End-of Study Visit. All AEs should be followed up 
according to Section 11.2. 
If a patient is withdrawn from the study, all data collected until the time of withdrawal will be 
used in the analyses.  
Survival data (including post-study survival data if applicable) will be collected and analyzed 
for all patients withdrawn from the study, Section 11.3. 
Patients randomized to Intuvax who withdraw from the study before administration of the first 
dose of Intuvax will be considered screening failures. Patients randomized to sunitinib alone 
who withdraw from the study before any assessments made at the first visit following 
Screening will be considered screening failures. 
Only patients considered screening failures will be replaced. 
8.6 
Premature Termination of the Study 
The Investigator or the Sponsor may terminate this study prematurely for any reasonable 
cause. The Institutional Review Board(s) (IRBs)/Independent Ethics Committee(s) (IECs) 
and Competent Authorities (CAs) should be informed promptly.  
Conditions that may warrant termination include, but are not limited to: 
• 
The discovery of an unexpected, significant, or unacceptable risk to the patients 
enrolled in the study, or potential study patients 
• 
A decision on the part of the Sponsor to suspend or discontinue development of 
Intuvax 
If the CA obtains information that raises doubts about the safety or scientific validity of the 
clinical study, the CA can suspend or prohibit the study. Before the CA reaches its decision it 
shall, except where there is imminent risk, ask the Sponsor and/or the Investigator for their 
opinion, to be delivered within one week (Directive 2001/20/EC, Article 12, Section 1). 
If the study is prematurely terminated or suspended for any reason, the 
Investigator/Institution should promptly inform the study patients and should assure 
appropriate therapy and follow-up for the patients. 
8.7 
Study Stopping Criteria 
Study stopping criteria are defined as: 
• 
Any death within 30 days of Intuvax administration that is not clearly attributable to 
surgery or disease progression 
• 
Any CTCAE grade 4 autoimmune disorder 
• 
Any toxicity that is unexpected, significant or unacceptable risk to the patients 
enrolled in the study, or potential study patients, Section 8.6 
The identification of a study stopping criterion in a patient will result in the permanent 
discontinuation of Intuvax in this patient and the enrolment will be temporarily held until an 
appropriate evaluation of the cause of the toxicity has been determined and a correction 
action plan is established if needed.  


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The medical monitor should be notified immediately and the patient should be followed for 
safety as clinically indicated until the toxicity resolves and in the opinion of the investigator, 
no further follow-up regarding the toxicity is needed (minimum of at least 30 days after last 
dose of IMP). 
 






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Sunitinib 
Per oral administration initiated five (5) to eight (8) weeks after nephrectomy for all patients 
Administered dose should be in accordance with the SmPC/USPI.  
In case of unacceptable sunitinib side-effects the standard on/off schedule of 4 weeks on/ 
2 weeks off (schedule 4/2) can be changed to 2 weeks on/1 week off (schedule 2/1). 
Retrospective data from patients treated with schedule 2/1 (50 mg/day) indicates superior 
PFS compared to those obtained with schedule 4/2. In addition, the reported safety profile 
and tolerance for schedule 2/1 justify its use in place of schedule 4/2 [29]. 
 
9.2 
Method of Assigning Patients to Treatment Groups 
At Screening the patient will be assigned a site specific screening number. This number will 
be generated automatically by Trial-on-Line, the electronic data capture (EDC) system used 
in the study. The screening number will be in the following format XX-YYYY. The letter XX is 
the site number and YYYY the consecutive patient number starting at 1001 at each site. The 
screening number will be used to identify the patient throughout trial participation. 
Two (2) randomization lists are generated by 
 using a global randomization system. 
One (1) to be used for randomization of high-risk patients and one (1) to be used for 
randomization of intermediate-risk patients. One (1) copy of each randomization list is kept in 
a sealed envelope in a locked cabinet at 
 and one (1) copy is sent to the IWRS provider. 
Randomization codes will be strictly sequential within blocks as patients are eligible for 
randomization. The randomization code will not be available to any person involved in the 
conduct or evaluation of the trial before the trial database is locked. 
When all results from the assessments made at Screening are available and the Investigator 
has confirmed eligibility and Heng-risk category for the patient the study coordinator will log 
into the IWRS and receive randomization and treatment information. The study nurse will 
make a telephone contact with the patient and inform about treatment and timing of next 
study visit. NB: If local regulations and laws require a confirmatory diagnostic biopsy before 
vaccination (i.e. systemic treatment) patients randomized to Intuvax will be booked for a 
biopsy collection visit prior to Vacc1 Visit. All participating US patients need a diagnostic pre-
biopsy made at Screening in order to evaluate eligibility for sunitinib treatment following 
nephrectomy. 
In case a patient randomized to Intuvax and sunitinib treatment withdraws prior to first dose 
of Intuvax or a patient randomized to sunitinib treatment only withdraws prior to any 
assessments made at the first visit following Screening they are considered screening 
failures, Section 8.5. A patient withdrawal contact will be performed via the IWRS allowing for 
additional patient inclusion until 90 patients have initiated study treatment. 
If a patient is not given treatment according to the randomization list, no attempt should be 
made to remedy the error once IMP has been dispensed. 
 must be notified as soon as 
the error is discovered and the error must be adequately documented. 
 
9.3 
Selection of Doses in the Study 
Intuvax 
The Intuvax dose to be administered in this study consists of 10 x106 viable and HLA class II 
expressing DCs. The outcome of Immunicum AB’s first-in-man study of Intuvax in RCC 




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Active control, dosage and mode of administration 
Sunitinib is the active control in this study, Section 9.1.1. Treatment (including dose 
adjustments etc.) will be in accordance with the SmPC/USPI from start of treatment. 
 
9.4 
Selection and Timing of Dose for Each Patient 
The patients will be randomized to treatment when the results from all assessments made at 
Screening are available.  
No time window between dosing of different patients applies in this study.  
The time window between Intuvax doses for the individual patient is 14 ±3 days. If the 
individual patient experiences a DLT in connection with first vaccination, Section 11.5 no 
second vaccination will be given to that patient. 
 
9.5 
Blinding  
This is an open label study. 
 
9.6 
Prior and Concomitant Therapy 
The following medications/therapies are prohibited during the study and within 28 days prior 
to Screening:  
• 
Other investigational products 
• 
Other systemic antitumor therapy.  
• 
Local radiation therapy to any area except for the abdominal/retropertioneal area 
including the kidney tumor is allowed. The impact of any palliative radiotherapy 
administered on evaluable lesions must be discussed with the Medical Monitor and 
documented in the eCRF 
The following medications are prohibited within 7 days prior to Screening Visit until 
Nephrectomy:  
• 
Systemic per oral corticosteroids exceeding 10 mg/day. However, inhaled, intranasal 
and local (per cutaneous) steroids for treatment of skin disorders, chronic obstructive 
lung disease, asthma, or allergy are acceptable irrespective of dose. 
Specific instructions in relation to the nephrectomy and Intuvax vaccinations: 
• 
Concomitant oral antithrombotic, e.g. acetylsalicylic acid (ASA), withdrawal and re-
start to be done according to local practice in connection with the nephrectomy and 
according to local practice for invasive examinations in connection with Intuvax 
vaccinations. 
• 
Anticoagulants, local practice applies for start and stop of anticoagulant treatment 
and shift to/use of low molecular weight heparin treatment in connection with 


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nephrectomy and according to local practice for invasive examinations in connection 
with Intuvax vaccinations 
Medication, which is considered necessary for the patient’s safety and well-being, may be 
given at the discretion of the Investigator as per local guidelines and Standard of Care. 
Whenever there is a medication available to prevent or alleviate a symptom it will be offered 
to the patient. 
Patients who respond inadequately to sunitinib treatment and need to change systemic anti-
cancer therapy should be scheduled for an End-of-Study Visit before being withdrawn from 
the study, Section 8.5. As described in Section 11.2 safety evaluation must also be 
performed up to 30 days after the patient’s last dose of IMP administered in the study. 
The use of all medication by the patient must be recorded in the eCRF, Section 10.4.4. 
In connection with the surgery various concomitant medications such as anesthesia, fluid 
substitution/blood substitution are part of clinical routine and these concomitant medications 
should not be recorded in the eCRF. Only concomitant medications not normally used in 
connection with the post-operative course after nephrectomy should be recorded in the 
eCRF. 
 
9.7 
Treatment Compliance 
Intuvax 
Administration will be done at the clinic by trained study personnel. Treatment compliance 
will be accomplished by documenting in record (i.e. the drug accountability, preparation, 
administration logs, the patients’ eCRF and medical records) information on, but not limited 
to: the batch number of the IMP used, the time-point for preparation/thawing, the time-point 
for administration, if CT or Ultrasound was used for confirmation of administration location, 
and signatures of designated site staff preparing and administering the IMP. 
Any deviations will be documented on the appropriate eCRF page. 
Sunitinib 
Patient compliance will be evaluated by unused tablet counts and check of empty packaging. 
Patients will be asked to return all unused and empty packaging material at the next clinic 
visit. The number of unused tablets will be counted upon return and recorded in the drug 
accountability log kept at the site. The sunitinib compliance including any deviations will be 
documented in the patients’ eCRF.  
 
9.8 
Drug Accountability 
Intuvax and sunitinib accountability, i.e. documentation of deliveries and return between the 
manufacturer, storage center, pharmacy, and/or the clinic shall be maintained. 
It is the responsibility of the Investigator or trained designee to determine Intuvax and 
sunitinib accountability and complete the drug accountability log. 
Drug accountability will be reviewed by the monitor during interim site visits and at the 
completion of the trial. 
At the end of the study when overall drug accountability have been completed any unused 
IMP should be handled by the pharmacy according to instructions provided by the Sponsor. 


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A list of IMP, used, or returned must be prepared and signed by the Investigator or designee; 
an account must be given for any discrepancies. 
Copies of all Drug Receipt Confirmations, Returned Clinical Supplies Reconciliation Forms 
and Drug Accountability Logs will be retained in the study file. These forms are subject to 
regulatory inspection at any time. 
 
9.9 
Post Study Treatment 
Intuvax is an IMP under development and will consequently not be available for treatment of 
the patients after study completion. 
Immunicum AB will pay the patients’ sunitinib treatment during their participation in the study 
except for US patients who have health insurance that covers these costs as part of standard 
of care. 
After end of study participation, patients will continue treatment in accordance with clinical 
praxis, i.e. as per local guidelines and Standard of Care.  
 






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recommended to be no greater than 5 mm). At baseline and in follow-up, only the 
short axis will be measured and followed. 
• 
Baseline documentation of “Target” and “Non-Target” lesions 
All measurable lesions up to a maximum of 2 lesions per organ and 5 lesions in total, 
representative of all involved organs, should be identified as target lesions and 
recorded and measured at baseline. 
- 
Target lesions. 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. It may be the case that, on occasion, the largest lesion does not 
lend itself to reproducible measurement in which circumstance the next largest 
lesion which can be measured reproducibly should be selected. A sum of the 
diameters (longest for non-nodal lesions, short axis for nodal lesions) for all target 
lesions will be calculated and reported as the baseline sum diameters. If lymph 
nodes are to be included in the sum, then only the short axis is added into the 
sum. The baseline sum diameters will be used as reference to further 
characterize any objective tumor regression in the measurable dimension of the 
disease. 
- 
Non-target lesions. All other lesions (or sites of disease) including any 
measurable lesions over and above the 5 target lesions should be identified as 
non-target lesions and should also be recorded at baseline. Measurements of 
these lesions are not required, but the presence, absence, or in rare cases 
unequivocal progression of each should be noted throughout follow-up. 
b) Response Criteria 
Table 4 
Target Lesions Evaluation Criteria 
 
Table 5 
Non-Target Lesions Evaluation Criteria 
Complete Response (CR) 
Disappearance of all non-target lesions and 
normalization of tumor marker level 
Progressive Disease (PD) 
Appearance of one or more new lesions and/or 
unequivocal progression of existing non-target lesionsa 
Complete Response (CR) 
Disappearance of all target lesions. Any pathological 
lymph nodes (whether target or non-target) must have 
reduction in short axis to <10 mm. 
Partial Response (PR) 
At least a 30% decrease in the sum of the diameters of 
target lesions, taking as reference the baseline sum 
diameters 
Progressive Disease (PD) 
At least a 20% increase in the sum of the diameters of 
target lesions, taking as reference the smallest sum on 
study (this includes the baseline sum if that is the smallest 
on study). In addition to the relative increase of 20%, the 
sum must also demonstrate an absolute increase of at 
least 5 mm. (NB: the appearance of one or more new 
lesions is also considered progression). 
Stable Disease (SD) 
Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD, taking as reference the smallest 
sum diameters while on study 


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Incomplete Response/ Stable 
Disease (SD) 
Persistence of one or more non-target lesion(s) or/and 
maintenance of tumor marker level above the normal 
limits 
a Although a clear progression of “non-target” lesions only is exceptional, the opinion of the treating physician 
should prevail in such circumstances, and the progression status should be confirmed at a later time by the 
Investigator. 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment 
Sunitinib until disease progression/recurrence (taking as reference for PD the smallest 
measurements recorded since the treatment started). In general, the subject's best response 
assignment will depend on the achievement of the measurement criteria. 
Table 6 
Evaluation of Best Overall Response 
Target Lesions 
Non-Target Lesions 
New Lesion 
Overall response 
CR 
CR 
No 
CR 
CR 
Incomplete 
response/SD 
No 
PR 
PR 
Non-PD 
No 
PR 
SD 
Non-PD 
No 
SD 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
 
Subjects with a global deterioration of health status requiring discontinuation of treatment 
without objective evidence of disease progression at that time should be classified as having 
“symptomatic deterioration.” Every effort should be made to document the objective 
progression even after discontinuation of treatment. 
Note: For intermediate-risk patients included in the trial according to protocol versions before 
version Final 4.0, the first imaging assessment after nephrectomy will be used as baseline for 
evaluation of best overall response, irrespective of whether or not the imaging assessment 
coincided with sunitinib treatment start. Further details will be provided in the SAP. 
Definitions for Response Evaluation 
a) Confirmation of Response 
To be assigned a status of complete or partial response, changes in tumor measurements do 
not need to be confirmed by repeat assessments after the criteria for response are first met. 
b) Response rate  
To be evaluated as the highest observed score of response during the study after 
randomisation in the ordinal categories of CR, PR, PD, SD and “Not evaluable”. The 
response rate will be evaluated according to the Schedule of Study Events, Section 7.2.1. 
c) 
Objective response  
Is defined as the proportion of patients with CR and PR. 
d) Disease control rate (DCR) 
Also called Clinical Benefit Rate is defined as the proportion of subjects with CR or PR or 
Stable Disease (SD). 








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Full information about the patients’ Social Security Number and name is to remain 
confidential in the records of the respective Investigator. 
 
10.4.2 Medical and Surgical History 
MEDICAL AND SURGICAL HISTORY (EXCLUDING MRCC) 
Clinical relevant past and present medical and surgical diagnoses non-related to RCC will be 
recorded at Screening in the eCRF. Medical History will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA) version 17.1. 
MEDICAL HISTORY (MRCC) 
The following medical history related to mRCC will be collected at Screening: 
• 
Date of RCC diagnosis 
• 
Primary tumor stage as defined by the American Joint Committee on Cancer's 
(AJCC’s) TNM classification system [30] 
• 
RCC symptoms including severity grading (NCI CTCAE version 4.0) [2] 
The diagnosis of RCC will be confirmed by histopathological local assessment of tumor 
tissue after nephrectomy. 
 
10.4.3 Efficacy Assessments by Imaging 
The locally assessed CT scan in conjunction with screening is to verify patient eligibility. This 
scan will be performed within 3 weeks before the Screening Visit unless a CT scan has been 
done in clinical routine within 6 weeks prior to the Screening Visit. 
Brain imaging: every subject must have had a MRI of the brain during the screening period 
unless a brain imaging by (preferably by contrast enhanced) MRI or CT was performed within 
the 6 weeks before randomization date. The MRI brain may be replaced by a CT brain if the 
subject does not tolerate the MRI procedure.   
On study, MRI (preferably contrast-enhanced) of the brain (or contrast-enhanced CT if not 
possible otherwise) should only be performed on the indication of evocative neurological 
symptoms. 
Tumor response will be evaluated by means of CT preferably, contrast enhanced of the 
chest, the upper and lower abdomen (including pelvis) and all other suspected sites of 
disease. The tumor response will be evaluated according to RECIST v1.1. [1] at baseline and 
for all repeated measurements according to the Schedule of Study Events, Section 7.2.1. 
CT scan assessments will be done both by a local radiologist trained in the study protocol 
and by a central assessor at the designated imaging CRO, 
, without 
knowledge of the patients’ treatment assignment and Heng-risk profile. Central assessments 
will form the basis for endpoint evaluations (PFS, ORR, TTP, TTF and tumor response rate). 
Central assessments will be done in accordance with a separate study-specific imaging 
protocol provided by 
. 
A study specific instruction describing the handling, transferring, blinding, distribution, 
assessment, result processing, and filing of data will be handed out to all involved personnel. 
CT scans performed at Sun-Start Visit five (5) to eight (8) weeks after nephrectomy will be 
used for evaluation of PFS from start of sunitinib, Section 10.2.2.1. Note: For 
intermediate-risk patients included in the trial according to protocol versions before version 
Final 4.0, the first imaging assessment (i.e. CT scan) after nephrectomy will be used. 


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CT scans performed at Sun-Start Visit five (5) to eight (8) weeks after nephrectomy will be 
used for evaluation of response rate from start of sunitinib, Section 10.2.2.2. Note: For 
intermediate-risk patients included in the trial according to protocol versions before version 
Final 4.0, the first imaging assessment (i.e. CT scan) after nephrectomy will be used. 
Centrally assessed CT scans performed in conjunction with screening and at the first 
post-nephrectomy assessment will be used to assess tumor response rate between 
screening and the first imaging assessment (i.e. CT scan) post-nephrectomy. 
The following information will be collected and used for the assessments if response is CR, 
PR, PD, SD, or “Not evaluable”:  
• 
Date of Abdomen CT scan 
• 
Date of Thorax CT scan 
• 
Site of metastases (including specification of target and non-target lesions at Sun-
Start Visit five (5) to eight (8) weeks after nephrectomy see Section 10.2.2.2 and [1]) 
• 
Sum of the diameters for all target lesions, see Section 10.2.2.2 and [1] 
• 
New lesions, see Section 10.2.2.2 and [1] 
If CT cannot be used for some reason, MRI is acceptable. The same modality has to be used 
at all visits. 
 
10.4.4 Prior and Concomitant Medication/Therapy 
Prior medication/therapy is defined as medication/therapy administered prior to Screening 
Visit. All medication/therapy administered after Screening Visit are considered concomitant 
medication/therapy. Prior medication/therapy will be indicated as past or ongoing at 
Screening. 
Prior medications taken within one (1) month prior to Screening and current ongoing 
treatment will be recorded at the Screening Visit on the concomitant medication page of the 
eCRF. Changes in concomitant medications will be recorded at all following visits throughout 
the study. For information on Concomitant Medication restrictions, see Section 9.6. 
The following information will be collected and recorded in the eCRF: Drug name (product 
name), route, dose and units, frequency, indication, reference to AE if applicable, start date, 
end date or ongoing at the end of the study will be recorded. 
Coding of prior and concomitant medications will be done using World Health Organization 
(WHO) Drug Dictionary. 
 
10.4.5 Electrocardiogram (ECG) 
A standard 12-lead electrocardiogram (ECG) recording will be performed according to local 
practice at Screening for identification of any heart failure. An overall interpretation of the 
ECG as “Normal” or “Abnormal” will be done. If an abnormal finding is considered clinical 
significant the patient will not qualify for participation in the study. 
 
10.4.6 Serology 
Blood samples for HIV, HBV and HCV will be collected and analyzed at Screening. Presence 
of any of these infections is an exclusion criterion. 


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The analyses will be performed by local laboratories. Sampling methods and procedures will 
be in accordance with local routine care. The Blood samples should be labelled with the 
patient’s unique screening number. 
 
10.4.7 Human Leukocyte Antigen (HLA)-typing 
Blood samples will be taken at Screening for evaluating the patient’s HLA type. HLA-A, HLA-
B and HLA-DRB1 will be analyzed centrally by high resolution tissue typing assays at 
.  
The blood samples collected should be labelled with the patient’s unique screening number.  
The study specific Laboratory Manual, which will be provided to all sites participating in this 
study, will include full details on blood sample collection, processing, storage, and shipping 
requirements. All samples will be destroyed after analyses have been performed.  
 
10.5 Safety Assessments 
10.5.1 Safety Variables 
The following safety variables will be measured: 
• 
AEs 
• 
Physical Examination 
• 
Vital Signs 
• 
Laboratory Safety Assessments blood (hematology, clinical chemistry, and 
coagulation) and urine including pregnancy 
• 
Other Safety Measurements (auto- and alloimmunization) 
 
10.5.2 Adverse Events 
AEs will be recorded during the study period from Screening Visit to the completion of the 
End-of-Study Visit.  
SAEs will be recorded during the study period from Screening Visit to the completion of the 
End-of-Study Visit or up to 30 days after last dose of IMP administered in the study, 
whichever occurs later. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 
17.1. The severity of AEs will be graded using the NCI CTCAE version 4.0 [2]. For further 
information of definitions and reporting of AEs and SAEs, see Section 11 below. 
Medical conditions or diseases present before Screening Visit are only considered AEs if 
they worsen after Screening Visit. Non-serious events occurring after signing the Informed 
Consent Form (ICF) but before any assessments made at the Screening Visit are recorded 
as Medical History in the eCRF. 
 


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10.5.3 Physical Examination 
The timings of physical examinations are described in Section 7.2.1 and Table 2. A physical 
examination in accordance with this protocol includes:  
Skin, eye, ear, nose and throat, respiratory, cardiovascular, abdomen, lymphatic, and 
neurological/musculoskeletal (including reflexes) 
The outcome of the assessments will be recorded as “normal” or “abnormal”. Abnormal 
findings will be assessed as “clinically significant” or “not clinically significant”. 
Clinically significant findings at Screening will be documented as Medical History. Clinically 
significant findings after Screening will be documented as AEs, Section 10.5.2. 
 
10.5.4 Vital Signs 
Vital signs will be monitored throughout the study as safety variables at the time points 
described in Section 7.2.1 and in Table 2. In connection with vaccination and the 4-hour 
post-vaccination observation period, a detailed monitoring schedule applies, Table 3. The 
following assessments will be done and should be documented in the vital sign section of the 
eCRF: 
• 
Supine systolic and diastolic blood pressure (mmHg), after 5 minutes lying down 
• 
Supine heart rate (beats per minute), after 5 minutes lying down 
• 
Body temperature (°C) (according to local practice) 
• 
Height (cm), will be measured only at Screening Visit 
• 
Weight (kg), will be measured at all visits except for Vacc1 and Vacc2 Visits 
 
10.5.5 Laboratory Safety Assessments (Blood and Urine) 
Blood and urine samples collected should be labelled with the patient’s unique screening 
number at all study visits. The study specific Laboratory Manual, which will be provided to all 
sites participating in this study, will include full details on blood sample collection, processing, 
storage, and shipping requirements (as applicable). All samples will be destroyed after 
analyses have been performed.  
BLOOD 
The centrally performed hematology and clinical chemistry analyses will be performed on 
serum samples by 
 
The coagulation (PT-INR and APTT) and pregnancy analyses will be performed by local 
laboratories in accordance with local routine.  
In addition to the central analysis of Hb, WBC and platelets, local analysis will be made prior 
to the vaccinations. Following hospital practice locally analyzed results of Hb, WBC, platelets  
and clinical chemistry might be needed prior to Nephrectomy unless results from central 
analyses within 14 days prior to Nephrectomy are available and acceptable. Sampling 
methods and procedures will be in accordance with local routine for these analyses.  
The timing of these assessments is described in Section 7.2.1, Section 7.2.2, and Table 2. At 
Vaccination Visits, blood samples will be collected prior to vaccination in connection with 
admission. If needed, for logistical reasons, these samples may be taken the day before 
vaccination. Also at Nephrectomy blood samples may be taken the day before for logistic 
reasons. 


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At least Hb, WBC, platelets, and coagulation status need to be available before vaccination 
and at least Hb, WBC, and clinical chemistry need to be available before nephrectomy. 
Analysis of coagulation status at Nephrectomy is not necessary provided the patient is not 
being treated with anticoagulants. For patients on anticoagulants local sampling practice 
applies. 
The following laboratory safety parameters will be measured in blood, Table 7: 
Table 7 
Laboratory Safety Parameters (Blood) 
Category 
Laboratory Parameter 
Hematology (central analysis 
and additional local analysis of 
Hb, WBC and platelets at 
Nephrectomy and Vaccination 
Visits) 
Hemoglobin (Hb), Red Blood Cells (RBC), White blood cells 
(WBC), Platelets, Neutrophils, Eosinophils, Basophils, 
Lymphocytes, and Monocytes 
Clinical Chemistry (central 
analysis  
C-Reactive Protein (CRP), Sodium (Na), Potassium (K), 
Creatininea, Albumin, corrected Calcium (Ca), Bilirubin, Lactate 
Dehydrogenase (LDH), Alkaline Phosphatase (ALP), Alanine 
Transaminase (ALAT), Gamma-Glutamyl Transferase (GGT), 
Aspartate Transaminase (ASAT), GFR based on Creatinineb, 
Glucb, TSHb, and Thyroxine (free T4)b 
Coagulation (local analysis) 
PT-INRc and APTTc  
Pregnancy (local analysis) 
human Chorionic Gonadotropin (hCG)d  
a Locally analyzed creatinine for patients included in the study before 28 August 2017 (if performed as part of 
clinical routine) to be recorded in the eCRF for Nephrectomy visit 
b To be analyzed at Screening, Sun-Start Visit and at all following visits until end of study 
c  To be analyzed at Screening, Nephrectomy and Vaccination Visits 
d To be analyzed in blood at Screening and in either blood or urine at vaccination visits, Table 8 
 
The observed values for all categories except pregnancy will be recorded and assessed as 
“normal” or “abnormal”. Abnormal findings will be assessed as “clinically significant” or “not 
clinically significant”. 
Pregnancy testing in blood will be done to females of childbearing potential at Screening for 
patients randomized to Intuvax. At Vaccination Visits the pregnancy testing can be done 
either in blood or urine. The results will be recorded as “Negative” or “Positive”. A patient with 
a positive test at Screening should not be included in the study. A patient with a positive test 
at either of the Vaccination Visits should be withdrawn from further study treatment, 
Section 11.7. 
URINE 
The laboratory safety urinalyses will be performed centrally 
. 
The timing of these assessments is described in Section 7.2.1 and Table 2. At Vaccination 
Visits, urine samples will be collected prior to vaccination in connection with admission. If 
needed, for logistical reasons, these samples may be taken the day before vaccination. 
The following laboratory safety parameters will be measured in urine, Table 8: 
Table 8 
Laboratory Safety Parameters (Urine) 
Category 
Laboratory Parameter 
Urinalysis (central analysis) 
U-Microalbumin, U-Red blood cells, U-Glucose, and U-Nitrite 


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Pregnancy (local analysis) 
Pregnancy dipsticka  
a To be analyzed in either blood or urine at Vaccination Visits and in blood at Screening 
 
Unless pregnancy testing at Vaccination Visits is done in blood, urine analysis using dipsticks 
will be done to females of childbearing potential at Vaccination Visits for patients randomized 
to Intuvax. The results will be recorded as “Negative” or “Positive” and need to be available 
before vaccination. A patient with a positive test at either of the Vaccination Visits should be 
withdrawn from further study treatment, Section 11.7. 
10.5.6 Other Safety Measurements  
10.5.6.1 Autoimmunization 
Blood samples will be taken from patients randomized to Intuvax at Vacc1 (prior to 
vaccination) and Sun-Start Visits to evaluate potential autoimmune events by screening of 
autoantibodies against clinically relevant autoantigens: 
• 
Anti-nuclear antibodies (IF-ANA) and kidney parenchyma-associated autoantigens 
(liver-kidney microsomal antigens and mitochondrial antigens). 
The analyses will be performed by 
. The blood samples collected 
should be labelled with the patient’s unique screening number at both study visits. The study 
specific Laboratory Manual, which will be provided to all sites participating in this study, will 
include full details on blood sample collection, processing, storage, and shipping 
requirements. All samples will be destroyed after analyses have been performed.  
The IF-ANA results will be recorded and assessed as “Negative” or “Positive”. Additional 
assessment of “Weak” or “Strong” will be done for positive results on Homogenous, 
Speckled, Nucleolar, and Centromere patterns. 
 
10.5.6.2 Alloimmunization 
Blood samples will be taken from patients randomized to Intuvax at Vacc1 (prior to 
vaccination) and Sun-Start Visits to evaluate potential vaccine-induced alloimmunization at 
the humoral level by screening of alloantibodies against HLA-A, B, C (HLA class I) and HLA-
DR, DQ, DP (HLA class II) antigens.  
The analyses will be performed by 
 
. The blood samples collected should be labelled with the 
patient’s unique screening number at both study visits. The study specific Laboratory 
Manual, which will be provided to all sites participating in this study, will include full details on 
blood sample collection, processing, storage, and shipping requirements. All samples will be 
destroyed after analyses have been performed. 
The results will be recorded and assessed as “Present” or “Not present”. 
 
10.6 Appropriateness of Measurements 
Standardized methods for measurements of efficacy and safety variables will be used. 


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11 
ADVERSE EVENTS 
11.1 Definitions 
11.1.1 Adverse Event 
Any untoward medical occurrence in a patient or clinical trial patient administered a medicinal 
product and which does not necessarily have a causal relationship with this treatment. 
Comment: An AE can therefore be any unfavourable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of an 
IMP, whether or not considered related to the IMP. 
11.1.2 Adverse Reaction 
All untoward and unintended responses to an IMP related to any dose administered. 
Comment: All AEs judged by either the reporting Investigator or the Sponsor as having a 
reasonable causal relationship to a medicinal product qualify as adverse reactions. The 
expression reasonable causal relationship means to convey in general that there is evidence 
or argument to suggest a causal relationship. 
11.1.3 Unexpected Adverse Reaction 
An adverse reaction, the nature or severity of which is not consistent with the applicable 
product information (e.g. Investigator's Brochure for an unauthorized IMP or SmPC/USPI for 
an authorized product). 
Comment: When the outcome of the adverse reaction is not consistent with the applicable 
product information this adverse reaction should be considered as unexpected. 
11.1.4 Serious Adverse Event 
Any untoward medicinal occurrence or effect that at any dose: 
• 
Results in death 
• 
Is life-threatening 
• 
Requires hospitalization or prolongation of existing hospitalization 
• 
Results in persistent or significant disability or incapacity 
• 
Is a congenital anomaly or birth defect 
Comments: Life-threatening in the definition of a serious adverse event (SAE) or serious 
adverse reaction refers to an event in which the patient was at risk of death at the time of 
event; it does not refer to an event which hypothetically might have caused death if it was 
more severe. 
Medical judgment should be exercised in deciding whether an AE/reaction is serious in other 
situations. Important AEs/reactions that are not immediately life-threatening or do not result 
in death or hospitalization but may jeopardize the patient or may require intervention to 
prevent one of the other outcomes listed in the definition above, should also be considered 
serious. 
11.2 Reporting of Adverse Events 
Adverse event reporting and data management will be performed according to the following 
relevant guidelines: 


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• 
Directive 2001/20/EC (European Clinical Trial Directive), 
• 
CPMP/ICH/E2A/377/95 (Clinical Safety Data Management: Definition and Standards 
for Expedited Reporting), 
• 
CPMP/ICH/135/95 (GCP), 
• 
21 CFR 312.32 (FDA). 
All study patients will be carefully monitored for the occurrence of AEs during the study 
period from Screening Visit to the completion of the End-of-Study Visit. SAEs will be 
collected until completion of the End-of-Study Visit or up to 30 days after last dose of IMP 
administered in the study, whichever occurs later. 
All patients who received IMP who withdraw less than 1 month after IMP administration must 
have safety evaluations, defined as recording and reporting of any SAE, for 30 days after the 
last dose of Intuvax or Sunitinib. The Investigator will collect AEs with a non-leading question 
such as “have you experienced any new health problems or worsening of existing conditions” 
as well as reporting events directly observed or spontaneously volunteered by patients. 
Clearly related signs, symptoms and abnormal diagnostic procedure results should be 
grouped together and reported as a single diagnosis or syndrome whenever possible. 
All AEs including but not limited to events reported by the patient, or reported in answer to an 
open question by the Investigator or member of this team, which fall into any of the above 
definitions must be recorded as an AE in the eCRF and should include the following 
information: 
• 
Brief description of the event (diagnosis) 
• 
Start date (and time, if relevant) 
• 
Stop date (and time, if relevant) (or resolution) 
• 
Severity 
• 
Action taken regarding IMP 
• 
Opinion on causality 
• 
Seriousness 
• 
Outcome 
The general term “Progressive Disease” (PD) should not be used when reporting an AE. 
Instead, all symptoms, laboratory findings etc. including those that could be a reflection of PD 
should always be reported. 
Severity describes the intensity of an event, and will be assessed using the NCI CTCAE 
version 4.0 [2]. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of 
severity for each AE based on this general guideline. The term Grade refers to the severity of 
the AE. The following grades are used: 
Grade 1 (Mild) 
Asymptomatic or mild symptoms OR clinical or diagnostic observations only OR intervention 
not indicated. 
Grade 2 (Moderate) 
Minimal, local or noninvasive intervention indicated OR limiting age-appropriate instrumental 
Activities of Daily Living (ADL). (Instrumental ADL refer to preparing meals, shopping for 
groceries or clothes, using the telephone, managing money, etc.) 


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Grade 3 (Severe or medically significant but not immediately life-threatening)  
Hospitalization or prolongation of hospitalization indicated OR disabling OR limiting self-care 
ADL. (Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, 
taking medications, and not bedridden.) 
Grade 4 (Life-threatening consequences)  
Urgent intervention indicated. 
Grade 5 (Death related to AE) 
If an AE changes in severity, the worst severity should be reported. 
Causality 
Causality will be assessed as: 
Probable 
A clinical event, including laboratory test abnormality, with a reasonable time sequence to 
administration of the IMP, unlikely to be attributed to concurrent disease or other drugs or 
chemicals, and which follows a clinically reasonable response on withdrawal (dechallenge). 
Rechallenge information is not required to fulfil this definition. 
Possible 
A clinical event, including laboratory test abnormality, with a reasonable time sequence to 
administration of the IMP, but which could also be explained by concurrent disease or other 
drugs or chemicals. Information on IMP withdrawal may be lacking or unclear. 
Unlikely 
A clinical event, including laboratory test abnormality, with a temporal relationship to IMP 
administration which makes a causal relationship improbable, and in which other drugs, 
chemicals or underlying disease provide plausible explanations. 
Follow-up of Patients after Adverse Events 
Any AE that is ongoing when the patient is withdrawn from the study should be followed up 
until the AE is resolved or the Investigator decides that the AE is stable and needs no further 
follow-up. 
Abnormal Laboratory Values/Vital Signs 
The reporting of abnormalities as both laboratory/vital signs findings and AEs should be 
avoided. 
An asymptomatic abnormal laboratory/vital sign finding should only be reported as an AE if it 
is clinically significant, if it fulfils the criteria for an SAE or if it causes the patient to 
discontinue the study. 
If an abnormal laboratory/vital sign value is associated with clinical signs and symptoms, the 
sign/symptom should be reported as an AE and the associated laboratory/vital sign result 
should be considered additional information. 
Safety Evaluation 30 Days after Last Dose of Investigational Medicinal Product 
All patients who have received IMP will have a safety evaluation, i.e., recording of SAEs for 
30 days after last dose of IMP. The safety evaluation will be performed either as (i) a visit to 


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the clinic by the patient, (ii) a phone call to the patient by site personnel, or, if contact with the 
patient is not possible for any reason, (iii) as a review of the patient’s medical records. All 
SAEs detected during the safety evaluation will be recorded in the eCRF and reported to 
 Drug Safety in accordance with the procedure presented in Section 11.3. 
 
11.3 Reporting of Serious Adverse Events 
The Investigator is responsible for ensuring that all SAEs are reported to the Sponsor 
immediately, but in any event no later than 24 hours of any site staff becoming aware of the 
event. Initial reports should be followed as soon as possible by detailed written reports. The 
initial and follow-up reports should identify patients by unique code numbers assigned in the 
study. The patient’s names, personal identification numbers, and/or addresses must not be 
included. The following information is mandatory for the initial report: 
• 
Patient study ID 
• 
Study treatment (blinded, if applicable) 
• 
Start date (time, if relevant) of the study treatment 
• 
Brief description of the event (diagnosis) 
• 
Start date (time, if relevant) of the event 
• 
Seriousness criteria 
• 
Causality assessment 
For reported deaths, the Investigator should supply the Sponsor and the IRB/IEC (if 
applicable) with any additional requested information (e.g. autopsy reports and terminal 
medical reports). 
Detailed instructions describing the procedure of reporting SAEs including Suspected 
Unexpected Serious Adverse Reactions (SUSARs), Section 11.4, will be distributed to the 
site and all involved parties at the Sponsor and 
 prior to study start. 
As a principle, all SAEs must be documented and medically assessed by the Investigator 
and the outcome described in the AE section of the eCRF. 
Follow-up of Post-Study Survival Information 
Sites having patients who are still alive after the entire study has ended will be asked to seek 
survival information in medical records or databases (including public records). 
The patient’s survival information after the patient’s End-of-study Visit will be reported to the 
safety database only, i.e. will not be included in the clinical database. A survival report form 
should be used for such reporting.  
Post-study survival information will be collected as follows: 
• 
Collection of survival data for the individual patient; at the 18 months post 
randomization time point 
• 
A complete collection for all applicable patients; at the time of study end (Section 7.5) 
• 
A complete collection for all applicable patients; at the last patient’s 18 months post 
randomization time point and thereafter yearly up to 5 years 
Updated information on median OS, will be reported to the authorities/IRBs/IECs as 
addendum(s) to the Clinical Study Report and also as part of the development safety update 
reports (DSURs).  


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SAE REPORTING CONTACT DETAILS 
 
 
  
 
 
 
 
11.4 
SAE and SUSAR Reporting to CAs, IRBs/IECs, and Investigators 
The Sponsor is responsible for informing all concerned CAs, IRB/IECs, and all clinical study 
investigators utilizing Intuvax of any individual case reports of SAEs that are determined to 
be reportable by the Sponsor (i.e. SUSARs). For a SUSAR that is fatal or life-threatening, 
this should be reported as soon as possible and not later than 7 days after the Sponsor was 
first advised, for any other SUSAR this should be within 15 days. In addition to SUSARs, the 
Sponsor is also responsible for reporting any unanticipated events that may place other 
patients or the study at risk. 
The Investigator will ensure that all relevant information is provided to the Sponsor to allow 
the Sponsor to meet their obligations to report the SUSAR to the CAs and IRBs/IECs. 
Furthermore, it is the responsibility of the Investigator to comply with any applicable site-
specific requirements related to the reporting of SAEs (other than SUSARs) involving his/her 
patients to the IRB/IEC that approved the trial. The Sponsor must obtain adequate 
documentation showing that the IRB/IEC was properly and promptly notified as required. 
 
11.5 Dose Limiting Toxicity (DLT) 
The following AEs are classified as DLTs: 
• 
Any AE of CTCAE grade 3 or higher (except for fever CTCAE grade 4 as this is an 
expected sign of immunologic response after vaccination), and assessed as possibly 
or probably related to Intuvax within the interval between the first vaccination and the 
subsequent one (i.e. the DLT observation period) 
• 
Any autoimmune reaction CTCAE grade 3 or higher probably or possibly related to 
Intuvax within the interval between the first vaccination and the subsequent one. 
If a patient experiences an AE that is qualified as DLT after first vaccination the second dose 
of vaccine will not be administered to the patient, Section 8.5. 
All DLTs, irrespectively of seriousness, must be reported to the CRO using the same 
procedures and in the same timelines as is applicable for SAEs. 
A DLT should be reported as an AE assessed as possibly or probably related to Intuvax as 
applicable. If a DLT fulfils any criterion for an SAE it should be reported as such. 
 


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11.6 Precautions/Overdose 
Preparedness for anaphylaxis treatment in connection with vaccination is required. No 
antidote for Intuvax is available. In the event of overdose symptomatic management is 
indicated.  
 
11.7 Pregnancy 
Contraception is to be used from Screening until 90 days after last dose of Intuvax and/or 
until completed sunitinib treatment whichever occurs later. 
Female patients will be instructed to notify the Investigator immediately if they become 
pregnant during the study. Male patients will be instructed to notify the Investigator 
immediately if their partner becomes pregnant. Pregnant patients will be withdrawn from 
further study treatment. The patients will also be instructed to report pregnancies discovered 
after the last visit, if they believe that conception occurred during their participation in the 
study. 
A pregnancy as such is not an AE, unless there is a possibility that the IMP has interfered 
with the efficiency of any contraceptive measures. However, the Investigator should report 
pregnancies according to the procedures and timelines described for reporting of SAEs 
(Section 11.3). The pregnancy report form should be used instead of the SAE form. 
The pregnant patient or partner will be followed until the end of the pregnancy. Any 
complication during the pregnancy should preferably be reported as an AE. The outcome of 
the pregnancy must be reported on the pregnancy report form. Any spontaneous abortion, 
stillbirth, birth defect/congenital anomaly, death, or other serious infant condition must be 
reported and followed up as an SAE. 


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12 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
12.1 Statistical and Analytical Plans 
A separate SAP, which will provide the technical details of the statistical analysis outlined 
below, will be prepared and approved before study data analysis, including any interim 
analysis. 
12.1.1 Data Sets to be Analyzed 
The analysis population sets, which will be defined separately by stratum, are defined as 
follows: 
Full analysis set (FAS): All patients randomized being evaluable for any high or 
intermediate stratum related efficacy endpoint. 
Per protocol set (PPS): All patients randomized to Intuvax who had both doses of Intuvax 
administered or subject randomized to sunitinib alone, both having the nephrectomy and who 
continued the trial without any major protocol violations that could interfere with the 
objectives of this study. 
Analyses of primary endpoints related to each stratum will be repeated using the PPS. 
Subgroups will furthermore be defined separately by stratum, as patients exposed to at least 
one dose of sunitinib and having following evaluable PFS. 
Safety set: All randomized patients who have at least one (1) assessment made at 
Screening. 
Safety summaries will be performed on the safety set. 
 
12.1.2 Definitions 
For definitions used for endpoint evaluation, see Section 10.2.1 and Section 10.2.2. 
 
12.1.3 Statistical Issues 
As this study is exploratory, sample size is not based on typical power calculation for 
confirming an efficacy as this would require either a too long follow-up or an unrealistic 
number of patients. Statistical hypothesis testing will be used but to be interpreted as 
exploratory analysis results. No adjustment for multiplicity will be done. All tests will be 
two-sided and type-1 error level is set to 0.05, i.e. significance level. 
Handling of missing data will be described in detail in the SAP. 
 
12.1.4 Summary Statistics 
In general, data will be summarized by means of summary statistics. Continuous data will be 
presented with the number of observations, mean value, standard deviation, minimum, Q1, 
median, Q3 and maximum value. Categorical data will be presented as counts and 
percentages. Visit related data will be summarized up until and including the Nephrectomy 
Visit. Following this visit, visit related data may in addition be summarized, if applicable, 
based on results being re-allocated defined based on time intervals or as last available 
observation. Details for this will be specified in the SAP. 


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All individual patient data will be listed. 
 
12.1.5 Primary Efficacy Analyses 
Two primary endpoints are defined, each one in relation to the two primary objectives. As this 
trial is not powered to detect a statistical significant difference between treatment groups, 
Section 12.2, the statistical analyses described below should be considered exploratory. No 
adjustments for multiple testing will be done. 
All patients will be followed for survival until date of death can be confirmed or up to 5 years 
after collection of the last patient’s 18 months survival data, whichever comes first. Post-
study survival data will be collected as described in Section 11.3. The primary analysis will 
be conducted based on the data collected at the entire study end. If the time point for the 
collection of post-study survival data at the entire study end, before DBL, differs with more 
than 2 months compared to the last patient’s 18 months post randomization time point, then 
an additional collection of survival data will be conducted and the first follow-up analysis of 
post-study survival data will be done, as described in Section 12.5.  
OS 
The primary endpoint median OS after randomization in high-risk and intermediate-risk 
mRCC patients will be calculated and compared overall and by subgroup using the FAS in 
the following way: 
Survival functions will be displayed graphically using Kaplan-Meier plots, and life table 
statistics will be produced including summaries of number of events and censored 
observations. Estimates of 25%, 50% (median) and 75% percentiles of time of survival with 
corresponding 95% confidence intervals will be calculated. Analysis where the survival 
functions will be compared between Intuvax+sunitinib, vs. sunitinib alone will be conducted 
using a log-rank test. Time to death in this analysis will be defined as the time from 
randomization until the event occurs.  
In addition the primary efficacy endpoint will be evaluated using the PPS. 
18-month survival rate 
The primary endpoint 18-month survival rate after randomization in high-risk and 
intermediate-risk mRCC patients will be calculated and compared overall and by subgroup 
using life table statistics including summaries of number of events and censored 
observations and similar survival statistics as described for the analysis of OS above.  
NB: Patients alive at the End-of-Study Visit will be followed for survival until date of death can 
be confirmed or for a maximum of 5 years after collection of the last patient’s 18 months 
survival data, whichever comes first.  
Lost to follow-up patients will be handled as censored observations if date of death cannot be 
found from medical records or databases (including public records). 
12.1.6 Secondary Efficacy Analyses 
Secondary efficacy endpoints will be presented descriptively by stratum (High-/Intermediate-
risk mRCC patients) as stated explicitly for each endpoint below. Further analyses may be 
defined in the SAP, if appropriate. All secondary endpoints will be evaluated using the FAS. 
In addition, the PPS will be used. 




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Study Code: IM-201 
Date: 12 February 2019 
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12.1.9 Demographic and Other Baseline Characteristics 
A patient disposition will be made including number of patients randomized, exposed to trial 
drug and completing, or withdrawal from trial (including reason for withdrawal). The number 
of patients in each analysis set will be included. The patient disposition will be made 
separately by stratum and overall. 
Demographic, medical surgical history and other baseline data will be presented using 
summary statistics based on the safety set overall and split by stratum. 
 
12.1.10 
Exposure to Treatment 
All details collected in relation to the Intuvax vaccination will be listed and tabulated if 
applicable. Nephrectomy data will be listed. Exposure data for sunitinib use will be listed per 
treatment group and stratum. 
 
12.1.11 
Concomitant Treatment 
Concomitant medication and concomitant therapy will be summarized as number of patients 
being treated with each type of medication/therapy classified according to ATC level 3 and 
WHO Drug Dictionary preferred term. The safety set will be used for this presentation. 
 
12.1.12 
Adverse Events 
Analyses of AEs will be based on the Safety set. AEs will be coded using MedDRA. 
The total number of AEs will be summarized including the number of patients with at least 
one (1) AE, the total number of AEs, the number of unique AEs per treatment group and in 
total. The number of AEs per severity (CTCAE) and relation to trial drug will also be included 
and summarized per treatment group and in total. SAEs will be summarized in a similar 
manner. 
The number of patients and the number of AEs will be tabulated by MedDRA system organ 
class and preferred term. AEs will also be tabulated versus worst severity and worst 
relationship to treatment. In this table, patients with AEs will be identified by their patient 
number. 
AEs occurring during the 4 hours following the Intuvax vaccination will in addition be 
summarized separately. 
Pretreatment events occurring between first assessment at Screening and first Intuvax dose 
(for vaccinated patients) and between first assessment at Screening and Nephrectomy (for 
unvaccinated patients) will in addition be summarized separately. 
All AEs summaries will be made overall and separately by stratum. 
 
12.1.13 
Other Safety Assessments 
Physical Examination 
Physical examination data will be summarized by visit and treatment group as described in 
Section 12.1.4. 


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Vital Signs 
Vital signs will be summarized by visit and treatment group, together with changes from 
Screening as described in Section 12.1.4. 
Vital signs assessed during vaccination, will be summarized both by nominal time point and 
as change from the pre-vaccination at each post-vaccination time point. 
Laboratory Safety Assessments 
For laboratory data, summary statistics will be produced for observed values and for changes 
from screening to each visit as described in Section 12.1.4. In addition, the number of 
abnormal and clinically significant observations will be tabulated for each treatment group by 
visit. Abnormal values will be flagged in listings. 
Shift tables will show the number of patients who changed from below, within or above the 
reference range at Screening to below, within or above the reference range at each time of 
assessment. 
12.2 Determination of Sample Size 
This is a proof of concept study and the number of patients chosen is based on practical 
considerations and not on a formal statistical power calculation. With around 90 patients 
randomized 2:1 to vaccination and control, it is expected that 18-month survival rate for high-
risk and intermediate-risk mRCC patients overall can be adequately estimated for exploratory 
purposes but not to confirm the findings as statistical significant. 
 
12.3 Procedures for Reporting any Deviation(s) from the Original Statistical Analysis 
Plan 
Any deviation(s) from the original SAP will be described and justified in a protocol 
amendment and/or in a revised SAP and/or in the final report, as appropriate. 
 
12.4 Interim Analysis 
An interim analysis is not planned for in this study.  
 
12.5 Follow-up Analysis of Post-Study Survival Data 
Survival data will be analyzed post-study end as described in Section 12.1.5 and Section 
12.1.6 and presented as addendum(s) to the final study report. Time-point(s) for analysis will 
be confirmed when considered justified by Immunicum AB and the Coordinating Investigator. 


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Study Code: IM-201 
Date: 12 February 2019 
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13 
INVESTIGATOR/SPONSOR RESPONSIBILITIES 
13.1 Ethics 
13.1.1 Institutional Review Boards/Independent Ethics Committees  and Competent 
Authorities 
This protocol and any amendments will be submitted to concerned competent authorities 
(CAs) and properly constituted IRBs/IECs, in accordance with the International Conference 
on Harmonisation (ICH) guidelines, the applicable European Directives, the applicable 
sections of the US CFR, and/or other national and local legal requirements, for favorable 
opinion of the study. Favorable opinions must be obtained in writing before the first patient 
can be recruited. In addition to the protocol and any amendments the IRBs/IECs will review 
and approve any advertisements used for recruitment, as well as the informed consent 
documents, their updates (if any), and any other written materials given to the patients. 
13.1.2 Ethical Conduct of the Study 
The study will be conducted in compliance with the protocol, the applicable European 
Directives, US CFR sections that address clinical research studies, and/or other national and 
local legal requirements, ICH E6 good clinical practice (GCP) and the ethical principles of the 
latest revision of the Declaration of Helsinki as adopted by the World Medical Association. 
13.1.3 Patient Information and Consent 
All patients will receive written and verbal information regarding the study at a prior interview. 
This information will emphasize that participation in the study is voluntary and that the patient 
may withdraw from the study at any time and for any reason. All patients will be given the 
opportunity to ask questions about the study and will be given sufficient time to decide 
whether to participate in the study. 
Before any study-related procedures the ICF will be signed and personally dated by the 
patient (or their legally acceptable representative and/or witness, as applicable) and by the 
person who conducted the informed consent discussion. Local regulations and laws regulate 
who is authorized to conduct the informed consent procedure. 
The consent includes information that data will be recorded, collected, processed and 
protected in accordance with the European General Data Protection Regulation (2016/679) 
(GDPR). 
The patient information includes information that the patients have the right to request 
access to their personal study data and the right to request rectification of any data that is not 
correct and/or complete. Furthermore, that Immunicum AB or designee personnel whose 
responsibilities require access to personal data agree to keep the identity of each patient 
confidential. 
A copy of the patient information including the signed consent form will be provided to the 
patient. 
Extra consent for vaccination for patients randomized to the vaccine arm, to be taken after 
randomization if required by local regulations. 
 
13.2 Patient Records and Source Data 
The origin of source data in the study will be further specified for each study site in a 
separate document (“Origin of Source Data”).  


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It is the responsibility of the Investigator to record essential information in the medical 
records in accordance with national regulations and requirements. The following information 
should be included as a minimum: 
• 
A statement that the patient is in a clinical study 
• 
The identity of the study e.g. Study code 
• 
Patient unique screening number and/or patient number 
• 
That informed consent was obtained and the date 
• 
Diagnose and date of diagnosis 
• 
Dates of all visits during the study period 
• 
Any information relating to AEs 
• 
All treatments and medications prescribed/administered (including dosage) 
• 
Date of study termination 
• 
Patient health service identification number 
The Investigator is responsible for ensuring the accuracy, completeness, legibility and 
timeliness of the data recorded in the eCRFs. Data reported in the eCRF that are derived 
from source documents should be consistent with the source documents or the 
discrepancies should be explained. eCRFs will be monitored on a regular basis. 
 
13.3 Access to Source Data and Documentation 
The Investigator should guarantee access to source documents for the monitor and auditors 
as well as for inspection by appropriate regulatory agencies, and the IRB/IEC, if required. 
 
13.4 Monitoring 
Immunicum AB is responsible for selecting qualified clinical trial centers to participate in this 
clinical trial. Site management and monitoring is delegated to 
 and these activities are 
specified in detail in the Study Monitoring Manual. 
The monitor will visit the study site to ensure that the study is conducted and documented in 
accordance with this protocol, ICH GCP guidelines, regulatory requirements and any study 
specific documents such as monitoring manual and eCRF completion guidelines. 
Monitoring visits will be conducted to confirm that e.g.: 
• 
The investigational team is adhering to the study protocol 
• 
Informed consent has been obtained from all participants 
• 
AEs have been reported as required 
• 
Data are being accurately recorded in the eCRFs 
• 
IMP is being stored correctly and drug accountability is being performed on an on-
going basis 
• 
Facilities are, and remain, acceptable throughout the study 




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Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
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Essential documents should be retained according to applicable regulatory requirements of 
the country(ies) where the product is approved, and/or where the Sponsor intends to apply 
for approval. 
It is the responsibility of the Sponsor to inform the Investigator/Institution in writing as to 
when the documents no longer need to be retained.  
 
13.9 Protocol Deviations 
Deviations to the study protocol will be documented in a Protocol Deviation Log. 
The classification of patients into protocol deviators will be made during a meeting before 
database lock. The classification will be mutually agreed between the Sponsor and 
 
before breaking the randomization codes. Listings will indicate the allocation of patients by 
analysis set and the number of patients per analysis set will be recorded in the clinical study 
report. 
Any Serious Breaches that substantially affect the integrity or the safety of the patients or the 
scientific validity of the study will be reported to the relevant authorities in accordance with 
local regulatory requirements. 
 
13.10 Protocol Amendments 
If the study protocol needs to be substantially amended, the amendment must be approved 
by the CA and/or the IRB/IEC, as appropriate, before implementation, except for an 
amendment resulting from an immediate hazard to the patients. Approval must also be 
obtained for updates to the written Patient Information and ICF, when applicable. 
If an amendment to the study protocol substantially alters the trial design, or increases the 
potential risk to the patients, the patient information has to be updated and written informed 
consent must be obtained again for currently enrolled patients. The updated patient 
information and informed consent must be provided to additional patients prior to their entry 
into the trial. 
 
13.11 Insurance 
The Sponsor must provide insurance or must indemnify (legal and financial coverage) the 
Investigator/the institution against claims arising from the study, except for claims that arise 
from malpractice, negligence or non-compliance with the protocol.  
 
13.12 Report and Publication 
After completion of the study, a clinical study report will be prepared according to the ICH 
Guideline for Structure and Content of Clinical Study Reports (ICH E3) by 
 in close 
collaboration with the Investigator and the Sponsor. Post-study survival data will be amended 
to the report. 
All publications and presentations must be based upon the clinical study report.  


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Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
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All information supplied by the Sponsor in connection with this study will remain the sole 
property of the Sponsor and is to be considered confidential information. No confidential 
information will be disclosed to others without obtaining prior written consent from the 
Sponsor and will not be used except in the performance of this study. 
If an Investigator wishes to publish results from this clinical study, written permission to 
publish must be obtained from the Sponsor in advance. As some of the information regarding 
the IMP and development activities at the Sponsor may be of a strictly confidential nature, 
the Sponsor must first review any publication manuscript prior to their submission to journals, 
meetings or conferences. The time for review should not exceed three (3) months after 
receipt of manuscript. 
The Sponsor may choose to publish or present data from this study. If an Investigator is 
offered authorship, he/she will be asked to critically review the article for important 
intellectual content and approve the version to be published. The Sponsor has the right to 
use the results for registration and internal presentation and for promotion of the Sponsor’s 
commercial interests. 
 


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Sponsor: Immunicum AB (publ) 
Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
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14 
REFERENCE LIST  
1. 
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R et 
al. New response evaluation criteria in solid tumours: Revised RECIST 
guideline (version 1.1). Eur J Cancer. 2009; 45:228-47 
2. 
Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 
Published: May 28, 2009 (v4.03: June 14, 2010) U.S. Department of Health 
and Human Services, National Institutes of Health, National Cancer Institute 
3. 
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET et al. 
Toxicity and response criteria of the Eastern Cooperative Oncology Group. 
Am J Clin Oncol. 1982; 5(6):649-55 
4. 
Heng DYC, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C et al. 
Prognostic factors for overall survival in patients with metastatic renal cell 
carcinoma treated with vascular endothelial growth factor–targeted agents: 
Results from a large, multicenter study. J Clin Oncol. 2009; 27(34):5794-99 
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Karnofsky DA, Burchenal JH. The Clinical Evaluation of Chemotherapeutic 
Agents in Cancer. In: MacLeod CM (Ed), Evaluation of Chemotherapeutic 
Agents. Columbia Univ Press. Page 196 (1949) 
6. 
Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C. Epidemiologic and 
socioeconomic burden of metastatic renal cell carcinoma (mRCC): A literature 
review. Cancer Treat Rev. 2008; 34:193–205 
7. 
Heng DYC, Xie W, Regan MM, Harshman LC, Bjarnason GA, Ulka N et al. 
External validation and comparison with other models of the International 
Metastatic Renal-Cell Carcinoma Database Consortium prognostic model: a 
population-based study. Lancet Oncology, 2013,14:141-148 
8. 
Regan L, Braude PR, Hill DP. A prospective study of the incidence, time of 
appearance and significance of anti-paternal lymphocytotoxic antibodies in 
human pregnancy. Hum Reprod. 1991; 6:294 
9. 
Kugler A, Stuhler G, Walden P, Zöller G, Zobywalski A, Brossart P et al. 
Regression of human metastatic renal cell carcinoma after vaccination with 
tumor cell–dendritic cell hybrids. Nature Medicine. 2000; 6:332-6 
10. Märten A, Renoth S, Heinicke T, Albers P, Pauli A, Mey U, et al. Clinical 
Protocol; Allogeneic dendritic cells fused with tumor cells: Preclinical results 
and outcome of a clinical phase I/II trial in patients with metastatic renal cell 
carcinoma. Human Gene Ther. 2003; 14:483-494 
11. Höltl L, Ramoner R, Zelle-Rieser C, Gander H, Putz T, Papesh C et al. 
Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma 
with or without cyclophosphamide. Cancer Immunol Immunother. 2005; 
54:663-70 
12. Avigan DE, George DJ, Oh WK, Atkins MB, McDermott DF et al. Phase I/II 
study of vaccination with electrofused allogeneic dendritic cells/autologous 
tumor-derived cells in patients with stage IV renal cell carcinoma. J 
Immunother. 2007; Oct, 30(7):749-61 
13. Zhou J, Weng D, Zhou F, Pan K, Song H, Wang Q et al. Patient-derived renal 
cell carcinoma cells fused with allogeneic dendritic cells elicit anti-tumor 
activity: in vitro results and clinical responses. Cancer Immunol Immunother. 
2009; 58:1587-97 


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Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
EudraCT No.: 2014-004510-28 
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Page 81 of 87 
14. Chevreau C, Ravaud A, Escudier B, Amela E, Delva R, Rolland F et al. A 
phase II trial of sunitinib in patients with renal cell cancer and untreated brain 
metastases. Clin Genitourin Cancer. 2014;12:50-4 
15. Golshayan AR, George S, Heng DY, Elson P, Wood LS, Mekhail et al. 
Metastatic carcinoid renal cell carcinoma treated with vascular endothelial 
growth factor-targeted therapy. J Clin Oncol. 2009, 27:235-41 
16. Finke JH, Rini B, Ireland J, Rayman P, Richmond A, Golshayan A, et al. 
Sunitinib reverses type-1 immune suppression and decreases T-regulatory 
cells in renal cell carcinoma patients. Clin Cancer Res. 2008; Oct 
15;14(20):6674-82 
17. Xin H, Zhang C, Herrmann A, Du Y, Figlin R, Yu H. Sunitinib inhibition of Stat3 
induces renal cell carcinoma tumor cell apoptosis and reduces 
immunosuppressive cells. Cancer Res. 2009; March 15; 69(6): 2506–2513 
18. Amin A, Dudek A, Logan R, Holtzbierelin J, Master V, Pal S, et al. Prolonged 
survival with personalized Immunotherapy (ASG-003) in combination with 
Sunitinib in unfavorable Metastatic RCC (mRCC). ASCO 2013 Genitourinary 
Symposium, Abstract # 357 
19. An international phase 3 randomized trial of autologous dendritic cell 
immunotherapy (AGS-003) plus standard treatment of advanced renal cell 
carcinoma (ADAPT). www.clinicaltrialsregister.eu. EudraCT No. 2012-000871-
17 
20. Volpe A, Kachura JR, Geddie WR, Evans AJ, Gharajeh A, Saravanan A, et al. 
Techniques, safety and accuracy of sampling of renal tumors by fine needle 
aspiration and core biopsy. J Urol. 2007; Aug; 178(2): 379-386 
21. Weill D, Benden C, Corris PA, Dark JH, Davis RD, Keshavjee S et al. A 
consensus document for the selection of lung transplant candidates: 2014 - An 
update for the pulmonary transplantation council of the international society for 
heart and lung transplantation. J Heart Lung Transplant 2015 Jan;34(1): 1-15 
22. Batabyal P, Chapman JR, Wong G, Craig JC, Tong A. Clinical practice 
guidelines on wit-listing for kidney transplantation: consistent and equitable? 
Transplantation 2012 Oct 15;94(7): 703-713 
23. Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O et 
al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J 
Med 2007 Jan 11;356(2): 115-124  
24. Liumbruno G, Bennardello F, Lattanzio A, Piccoli P, Rossetti G. 
Recommendations for the transfusion of plasma and platelets. Blood Transfus 
2009 Apr;7(2): 132-150 
25. Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P et al. Sunitinib mediates 
reversal of myeloid-derived suppressor cell accumulation in renal cell 
carcinoma patients. Clin Cancer Res. 2009; 15(6):2148-2157 
26. Escudier B, Porta C, Schmidinger M, Algaba F, Patard JJ, Khoo V, et al. Renal 
cell carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and 
follow-up. Annals of Oncology 2014; 25 (Supplement3): iii49–iii56 
27. Motzer RJ, Jonasch E, Agrawal N, Beard C, Bhayani S, Bolger GB, et al. 
Kidney Cancer, Version 2.2014. Featured updates to the NCCN guidelines, 
J Natl Compr Cancer Network 2014; 12(2): 175–182 


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Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
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28. Motzer RJ, Jonasch E, Agrawal N, Bhayani S, Chang SS, Choueiri TK, et al. 
Kidney Cancer, Version 1.2016, 09/14/15, NCCC Clinical Practice Guidelines 
in Oncology (NCCN Guidelines®), National Comprehensive Cancer Network, 
Inc. 2015, http://www.NCCN.org 
29. Guida FM, Santoni M, Conti A, Burattini L, Savini A, Zeppola T et al. 
Alternative dosing schedules for sunitinib as a treatment of patients with 
metastatic renal cell carcinoma. Clinical Reviews in Oncology Hematology, 
2014 on line publication  
30. Kidney. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer 
Staging Manual. 7th ed. New York, NY: Springer, 2010; pp 479-89 










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Version: Final 9.0 
Study Code: IM-201 
Date: 12 February 2019 
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Page 85 of 87 
16 
CLINICAL STUDY PROTOCOL AGREEMENT FORM 
16.1 Clinical Study Protocol Agreement Form  
I have read the clinical study protocol entitled: “An open-label, randomized, controlled, 
multicenter, phase II study evaluating safety and efficacy of intratumorally administered 
Intuvax pre-nephrectomy followed by Sunitinib post-nephrectomy, compared to Sunitinib 
post-nephrectomy in metastatic renal cell carcinoma patients” and verified that it contains all 
necessary information for conducting the study. 
I hereby confirm that: 
• 
I have carefully read and understood this clinical study protocol 
• 
My staff and I will conduct the study according to the study protocol and will comply 
with its requirements, including ethical and safety considerations. 
I understand that, should the Sponsor decide to prematurely terminate or suspend the study 
for whatever reason, such decision will be communicated to me in writing. Conversely, if I 
decide to withdraw from execution of the study I will immediately communicate such a 
decision to the Sponsor. 
I agree not to publish any part of the results of the study carried out under this clinical study 
protocol without consulting the Sponsor. 
 
Principal Investigator: 
 
Study Site: 
 
Date: 
 
Signature:  
 





SAP_001.pdf: 
 
 
 
 
 
Official Title: Statistical Analysis Plan 
 
An open-label, randomized, controlled, multicenter, phase II study evaluating safety and efficacy of 
intratumorally administered Intuvax pre-nephrectomy followed by Sunitinib post-nephrectomy, 
compared to Sunitinib post-nephrectomy in metastatic renal cell carcinoma patients 
 
Document date: 2019-06-19 
 
NCT number: NCT02432846 
 
 


 
 
 
 
CONFIDENTIAL 
 
STATISTICAL ANALYSIS PLAN 
 
 
 
An open-label, randomized, controlled, multicenter, phase II study 
evaluating safety and efficacy of intratumorally administered Intuvax pre- 
nephrectomy followed by Sunitinib post-nephrectomy, compared to 
Sunitinib post-nephrectomy in metastatic renal cell carcinoma patients 
 
Sponsor Study Code: IM-201 
 
 
Sponsor 
Immunicum AB 
 
Product/Compound/Device Intuvax (preactivated allogeneic dendritic cells) 
Phase of the study 
II 
 
Author 
 
 
Company 
 
 
Address 
 
 
Telephone number 
 
Version 
Final 1.0 
Date 
2019-06-19 




Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
3 (30) 
 
 
 
 
TABLE OF CONTENTS 
 
1 
INTRODUCTION ........................................................................................................ 5 
2 
STUDY OBJECTIVES ................................................................................................ 5 
3 
EFFICACY AND SAFETY ENDPOINTS .................................................................... 6 
3.1 
Primary Efficacy Endpoints ........................................................................................ 6 
3.2 
Secondary Efficacy Endpoints .................................................................................... 6 
3.3 
 ................................................................................ 6 
3.4 
Safety Endpoints ........................................................................................................ 7 
4 
OVERALL STUDY DESIGN ....................................................................................... 7 
4.1 
Overview of Study Design .......................................................................................... 7 
4.2 
Determination of Sample Size .................................................................................. 14 
5 
DATA SETS TO BE ANALYSED ............................................................................. 14 
6 
STATISTICAL AND ANALYTICAL PLANS .............................................................. 15 
6.1 
Changes in the Planned Analyses ........................................................................... 15 
6.2 
Blind Review ............................................................................................................. 15 
6.3 
Hypotheses and Statistical Methods ........................................................................ 15 
6.3.1 
Definitions ................................................................................................................. 15 
6.3.2 
Summary Statistics ................................................................................................... 16 
6.3.3 
Patient Data Listings ................................................................................................ 16 
6.3.4 
Demographic and Other Baseline Characteristics ................................................... 16 
6.3.5 
Primary Efficacy analysis ......................................................................................... 16 
6.3.6 
Secondary Efficacy Analyses ................................................................................... 17 
6.3.7 
 ................................................................................ 20 
6.3.8 
Exposure to Treatment ............................................................................................. 22 
6.3.9 
Concomitant Medications ......................................................................................... 22 
6.3.10 
Adverse Events ........................................................................................................ 22 
6.3.11 
Other Safety Assessments ....................................................................................... 23 
6.4 
Level of Significance, Multiple Comparisons and Multiplicity ................................... 23 
6.5 
Adjustment for Covariates ........................................................................................ 23 
6.6 
Handling of Dropouts and Missing Data ................................................................... 23 
6.7 
Multicentre Studies ................................................................................................... 25 
6.8 
Examination of Subgroups ....................................................................................... 25 
6.9 
Interim Analysis ........................................................................................................ 25 
6.10 
Data Monitoring ........................................................................................................ 25 
7 
REFERENCES ......................................................................................................... 26 
8 
APPENDIX 1 ............................................................................................................ 26 
8.1 
Tables to be Produced for the Clinical Study Report (Section 14 according to 
ICH E3) ..................................................................................................................... 26 
8.2 
Listings of Individual Patient Data and Other Information to be Produced for the 
Clinical Study Report (Sections 16.1 and 16.2 in ICH E3) ....................................... 30 
 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
4 (30) 
 
 
 
 
 
ABBREVIATIONS 
AE 
Adverse Event 
CDM 
Clinical Data Manager 
CR 
Complete Response 
CRF 
Case Report Form 
CSP 
Clinical Study Protocol 
CSR 
Clinical Study Report 
DCR 
Disease Control Rate 
ECOG 
Eastern Cooperative Oncology Group 
FAS 
Full Analysis Set 
IMP 
Investigational Medicinal Product 
MedDRA 
Medical Dictionary for Regulatory Activities 
mRCC 
Metastatic Renal Cell Carcinoma 
OS 
Overall Survival 
ORR 
Object ve Response Rate 
PD 
Progress ve D sease 
PFS 
Progress on Free Surv va  
PPS 
Per Protocol Set 
PR 
Part a  Response 
 
 
RECIST 
Response Evaluation Criteria In Solid Tumors 
SAP 
Statistical Analysis Plan 
SD 
Stab e D sease 
SOC 
System Organ C ass 
TTF 
Time to Treatment Failure 
TTP 
Time to Tumor Progression 
WHO 
World Health Organization 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
5 (30) 
 
 
 
 
 
1 
INTRODUCTION 
 
This Statistical Analysis Plan (SAP) is based on Clinical Study Protocol (CSP) Version 9.0 
dated 12 February 2019 (and Version 9.1 dated 19 February 2019 for France). It should be 
noted that, prior to procol version 4.0, the trial design was different for intermediate risk 
patients, which leads to some specific considerations to be taken for subjects included in the 
trial corresponding to these versions. 
 
2 
STUDY OBJECTIVES 
 
The primary objectives are: 
• 
To evaluate median overall Survival (OS) from randomization in metastatic renal cell 
carcinoma (mRCC) patients overall and by subgroup, i.e. in high-risk and in 
intermediate-risk patients separately, receiving two (2) vaccine doses of Intuvax pre- 
nephrectomy, followed by sunitinib initiated five (5) to eight (8) weeks post- 
nephrectomy and in non-vaccinated mRCC patients receiving sunitinib initiated five 
(5) to eight (8) weeks post nephrectomy 
• 
To evaluate 18-month survival rate from randomization in mRCC patients overall and 
by subgroup, i.e. in high-risk and in intermediate-risk patients separately, receiving 
two (2) vaccine doses of Intuvax pre-nephrectomy followed by sunitinib post- 
nephrectomy and in non-vaccinated patients receiving sunitinib post-nephrectomy 
The secondary objectives are: 
• 
To evaluate safety and tolerability in high- and intermediate-risk mRCC patients 
receiving two (2) vaccine doses of Intuvax pre-nephrectomy followed by sunitinib 
post-nephrectomy and in non-vaccinated patients receiving sunitinib post 
nephrectomy 
• 
To evaluate progression free survival (PFS) according to Response Evaluation 
Criteria In Solid Tumors (RECIST) 1.1 criteria from Sunitinib Start Visit in 
intermediate- and high-risk mRCC patients after receiving two (2) vaccine doses of 
Intuvax pre-nephrectomy followed by sunitinib post-nephrectomy and in non- 
vaccinated patients receiving sunitinib post nephrectomy 
• 
To evaluate response and its duration according to RECIST 1.1 criteria from Sunitinib 
Start Visit in intermediate- and high-risk mRCC patients receiving two (2) vaccine 
doses of Intuvax pre nephrectomy followed by sunitinib post-nephrectomy and in non- 
vaccinated patients receiving sunitinib post-nephrectomy 
• 
To evaluate time to tumor progression (TTP) from Sunitinib Start Visit in intermediate- 
and high-risk mRCC patients receiving two (2) vaccine doses of Intuvax pre- 
nephrectomy followed by sunitinib post-nephrectomy and in non-vaccinated patients 
receiving sunitinib post-nephrectomy 
• 
To evaluate the number of infiltrating CD8+ T-cells in available diagnostic pre-biopsy 
(sample from either primary tumor or metastasis acceptable) and in the resected 
primary renal tumor in intermediate- and high-risk mRCC patients receiving two (2) 
vaccine doses of Intuvax pre-nephrectomy and in non-vaccinated patients 
 






Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
8 (30) 
 
 
 
 
• Time for diagnosis to treatment less than one (1) year 
• Neutrophils greater than ULN 
• Platelets greater than ULN 
 
The patients are randomized in a consecutive order to one (1) of the following two (2) 
treatment arms when eligibility has been confirmed; 
(i) 
Two (2) doses of Intuvax (10x106 DCs) administered intratumorally into the 
primary tumor 14 ±3 days apart followed by nephrectomy at least three (3) 
days after the second vaccine dose and sunitinib treatment initiated five (5) to 
eight (8) weeks after nephrectomy, administered dose in accordance with the 
SmPC/USPI. 
(ii) 
Sunitinib treatment initiated five (5) to eight (8) weeks after nephrectomy, 
administered dose in accordance with the SmPC/USPI. 
The expected number of patients to be randomized in the study is around 90. The patients 
are randomized in a 2:1 (vaccine treatment arm [i]:control treatment arm [ii]) ratio. 
Patients randomized to treatment arm (i) are scheduled for 12 study visits and patients 
randomized to treatment arm (ii) are scheduled for 10 study visits during a study period of 78 
weeks, see list below and Figure 1. The following vists apply for patients participating in the 
trial 
• 
Screening Visit (Screening) 
• 
Vaccination 1 Visit (Vacc1), applicable for patients randomized to treatment arm (i) 
• 
Vaccination 2 Visit (Vacc2), applicable for patients randomized to treatment arm (i) 
• 
Nephrectomy Visit (Nephrectomy) 
• 
Sunitinib Start Visit (Sun-Start), five (5) to eight (8) weeks after Nephrectomy 
• 
Sunitinib Follow-up Visits (SFU[6W] and SFU[12W]), every 6 weeks for 12 weeks or 
until locally CT-verified PD whichever occurs first 
• 
Sunitinib Follow-up Visits (SFU[24W], SFU[36W], SFU[48W], and SFU[60W]), every 
12 weeks until End-of study or until locally CT-verified PD whichever occurs first 
• 
End-of-Study Visit (End-of-Study) 
 
The above described visits are applicable to all randomized subjects after and including 
protocol version 4.0. Subjects entering the trial corresponding to protocol versions prior to 
this, were included following a visit pattern that was different for high and intermediate risk 
patients. Following this design intermediate risk subjects would only start sunitinib treatment 
after confirmed PD. 
At the two (2) Vaccination Visits, the patients are be administered Intuvax (10 x106 DCs) 
intratumorally in the viable part of their primary tumor. Vaccine from the same batch (i.e. the 
same donor) is be used at both occasions. The patient stay at the clinic at least four (4) 
hours after vaccination. Nephrectomy is done at least 3 days after the second vaccination 
and maximum 63 days after Screening. Sunitinib treatment is initiated five (5) to eight (8) 
weeks after nephrectomy, administered dose is in accordance with the SmPC/USPI. 
All patients areencouraged to contact the clinic in between study visits if they experience 
adverse events (AEs) or have any concerns. If follow-up of any symptoms is needed 
between the planned visits, the patient are scheduled for a visit as soon as possible and 
applicable assessments are performed. 
A diagram of the study design is provided in Figure 1, and a flow chart what all assessments 
to be conducted per visit are provided in Tables 1 and 2. 




Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
10 (30) 
 
 
 
 
Table 1 
Study Flow Chart 
 
Visit 
Screening 
Day 1 
Vacc1 
Intuvax + 
sunitinib: 
Day 2-28 
sunitinib 
only: 
N/A 
Vacc2 
Intuvax + 
sunitinib: 
Day 16-42 
sunitinib 
only: 
N/A 
Nephrectomy 
Intuvax + 
sunitinib: 
Day 19-63 
sunitinib 
only: 
Day 63 at the 
latest 
Sun-Start 
5 to 8 weeks 
after Nephr.j 
SFU[6W] 
SFU[36W] 
6w ±7d 
 
36w ±7d 
after Sun-Start 
after Sun-Start 
 
SFU[12W] 
SFU[48W] 
12w ±7d 
 
48w ±7d 
after Sun-Start 
after Sun-Start 
 
SFU[24W] 
SFU[60W]o 
24w ±7d 
 
60w ±7d 
after Sun-Start 
after Sun-Start 
End-of- 
Study 
78w ±2w 
after Screening 
Extra visit 
When needed 
Informed consent 
X 
Xs 
 
 
 
 
Demography 
X 
 
 
 
 
 
Med ca  and Surg ca  H story 
X 
 
 
 
 
 
CT/MRI scanl 
Xm 
 
Xt 
Xt 
Xt 
 
Pr or and/or Concom tant 
Med cat on 
X 
X 
X 
Xa 
X 
X 
X 
X 
Phys ca  Exam nat on 
X 
X 
X 
X 
X 
X 
X 
V ta  S gnsb 
X 
Xc 
Xc 
X 
X 
X 
X 
ECG 
X 
 
 
 
 
 
Hemato ogy and C n. Chem. 
X 
Xd 
Xd 
Xa d 
Xu 
X 
X 
X 
GFR based on Creat, G uc, 
TSH, and Thyrox ne (free T4) 
X 
 
X 
X 
X 
Xn 
PT-INR 
X 
Xd 
Xd 
Xa d 
 
 
 
 
APTT 
X 
Xd 
Xd 
Xa d 
 
 
 
 
Pregnancy 
Xe 
Xe 
Xe 
 
 
 
 
Ur na yses 
X 
Xd 
Xd 
Xa 
Xu 
X 
X 
X 
HIV/HBV/HCV and HLA 
X 
 
 
 
 
 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
11 (30) 
 
 
 
 
Cont. Table 2 Study Flow Chart 
 
Visit 
Screening 
Day 1 
Vacc1 
Intuvax + 
sunitinib: 
Day 2-28 
sunitinib 
only: 
N/A 
Vacc2 
Intuvax + 
sunitinib: 
Day 16-42 
sunitinib 
only: 
N/A 
Nephrectomy 
Intuvax + 
sunitinib: 
Day 19-63 
sunitinib 
only: 
Day 63 at the 
latest 
Sun-Start 
5 to 8 weeks 
after Nephr.j 
SFU[6W] 
SFU[36W] 
6w ±7d 
 
36w ±7d 
after Sun-Start 
after Sun-Start 
 
SFU[12W] 
SFU[48W] 
12w ±7d 
 
48w ±7d 
after Sun-Start 
after Sun-Start 
 
SFU[24W] 
SFU[60W]o 
24w ±7d 
 
60w ±7d 
after Sun-Start 
after Sun-Start 
End-of- 
Study 
78w ±2w 
after Screening 
Extra visit 
When needed 
Auto- and A o mmun zat on 
 
X  
X  
 
 
 
ECOG performance 
X 
Xd 
Xd 
X 
X 
X 
X 
Karnofsky performance 
X 
 
 
 
 
 
 
X 
 
Xa 
X 
X 
X 
 
Inc us on/Exc us on cr ter a 
Xg 
 
 
 
 
 
Random zat on 
Xg 
 
 
 
 
 
Conf rmatory d agnost c 
b opsy 
Xp 
 
 
 
 
 
Nephrectomy 
 
 
X 
 
 
 
 
B ops es (tumor x2, adjacent 
norma  t ssue) 
 
 
X 
 
 
 
 
Adm n strat on of Intuvaxq 
 
Xc 
Xc 
 
 
 
 
Sun t n b d spense & returnh 
 
 
Xi 
X 
Xi 
 
AEs 
X 
Xc 
Xc 
X 
X 
X 
Xk 
X 
D agnos s Conf rmat onr 
 
 
X 
 
 
 
 
a Assessment to be comp eted before nephrectomy and may be done the day before nephrectomy for og st ca  reasons 
Loca y ana yzed Creat n ne for pat ents nc uded n the study before 28 August 2017 ( f performed as part of c n ca  rout ne) to be recorded n eCRF 
b He ght on y at Screen ng. We ght at a  v s ts except for Vacc1 and Vacc2 V s ts. 
c See spec f c f ow chart, Table , for deta ed nstruct ons on pre- and post-vacc nat on assessments. 
d Phys ca  exam nat on, ECOG performance, and samp es for safety ab and ur na yses may be taken the day before vacc nat on for og st ca  reasons 
Loca y ana yzed resu ts for Hb, WBC, p ate ets, PT-INR, and APTT need to be ava ab e before vacc nat on 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
12 (30) 
 
 
 
 
Loca y ana yzed resu ts for Hb, WBC, and c n ca  chem stry m ght need to be ava ab e pr or to nephrectomy 
Ana ys s of coagu at on status at Nephrectomy s not necessary prov ded the pat ent s not on ant coagu ant treatment. For pat ents on ant coagu ants oca  samp ng pract ce 
app es. 
e Pregnancy test n b ood at Screen ng, and n e ther b ood or ur ne at Vacc1 and Vacc2 V s ts. The pregnancy test resu t s needed pr or to each vacc nat on. 
f 
Samp es for auto- and a o mmun zat on ana yses w  be co ected pr or to vacc nat on at Vacc1 V s t. Samp ng at Sun-Start V s t on y app cab e for pat ents random zed to 
Intuvax. 
g To be done when the resu ts from a  assessments made are ava ab e. Te ephone contact w th pat ent to nform about treatment and t m ng of next study v s t. 
h The prescr bed dose to be n accordance w th the SmPC/USPI nc ud ng any dose adjustments. 
 
Return of sun t n b not app cab e at Sun-Start V s t and D str but on not app cab e at End-of-Study V s t. Standard of Care app es after End-of-Study. 
j 
Start of sun t n b adm n strat on w  be dependent on wound hea ng. The t me w ndow for n t at on s f ve (5) to e ght (8) weeks after Nephrectomy. 
k Post-study co ect on of surv va  data. 
 
If CT cannot be used for some reason, MRI s acceptab e. The same moda ty has to be used at a  v s ts. 
m CT scan to be done w th n 3 weeks before Screen ng un ess a CT scan has been done n c n ca  rout ne w th n 6 weeks before Screen ng. Bra n mag ng (preferab y by 
contrast-enhanced) MRI or CT to be done w th n 3 weeks before Screen ng V s t un ess a CT scan has been performed n c n ca  rout ne w th n 6 weeks pr or to Screen ng 
V s t 
n To be done f Extra V s t s schedu ed after Sun-Start V s t 
o If SFU[60W] s schedu ed ≥76 weeks s nce Screen ng th s v s t shou d be cons dered the End-of-Study V s t 
p Conf rmatory d agnost c b opsy n accordance w th oca  rout nes pr or to Vacc1 V s t, f requ red by oca  regu at ons and aws 
q Abso ute fast ng for four (4) h pr or to Intuvax adm n strat on app es 
r 
Rout ne h sto ogy/Pr mary d agnos s s assessed oca y 
s 
Extra consent for vacc nat on for pat ents random zed to the vacc ne arm, to be taken after random zat on f requ red by oca  regu at ons 
t 
The CT scan does not have to be done the very same day as the correspond ng study v s t. However, each CT scan has to be done w th n the spec f ed t me w ndow for the 
correspond ng v s t 
u The aboratory safety b ood and ur ne assessments do not have to be done the very same day as the study v s t. However, t has to be done w th n 3 days pr or to the v s t. 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
13 (30) 
 
 
 
 
 
Table 2 
Assessments in Connection with Vaccination 
 
Assessment 
Pre- 
vacc nat on 
Vacc nat on 
Post-vacc nat on 
> 2 h 
0 h 
15 m n 
(±5 min) 
30 m n 
(±10 min) 
60 m n 
(±10 min) 
2 h 
(±10 min) 
3 h 
(±10 min) 
4 h 
(±20 min) 
Intuvax nject on 
 
X 
 
 
 
 
 
BP 
X 
 
X 
X 
X 
X 
X 
X 
HR 
X 
 
X 
X 
X 
X 
X 
X 
Body temperature 
X 
 
X 
X 
X 
X 
X 
AEs 
X 
 
X 
X 
X 
X 
X 
X 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
14 (30) 
 
 
 
 
 
4.2 
Determination of Sample Size 
This is a proof of concept study and the number of patients chosen is based on practical 
considerations and not on a formal statistical power calculation. With around 90 patients 
randomized 2:1 to vaccination and control, it is expected that 18-month survival rate for high- 
and intermediate-risk mRCC patients overall can be adequately estimated for exploratory 
purposes but not to confirm the findings as statistical significant. 
 
5 
DATA SETS TO BE ANALYSED 
 
The following analysis sets will be used for the statistical analysis and presentation of data: 
• 
The safety set: All randomized patients with at least one safety assessment at 
Screening. 
• 
The full analysis set (FAS): All randomized patients being evaluable for any efficacy 
endpoint 
• 
The per protocol set (PPS): All patients randomized to Intuvax who had both doses 
of Intuvax administered or patient randomized to sunitinib alone, both having the 
nephrectomy and who continued the trial without any major protocol violations that 
could interfere with the objectives of this study. The criteria for PPS, regarding which 
protocol deviations that warrant exclusions will be determined by the following criteria. 
• 
Violations to inclusion, exclusion and withdrawal criteria 
• 
Deviations relating to primary and secondary objectives/endpoints 
• 
Study medication (Intuvax or Sunitinib): That was not stored and/or prepared 
and/or administered as defined in the protocol 
• 
Administration of prohibited concomitant medication 
• 
Availability of required data 
 
The exact criteria that warrant exclusion from PPS will be documented in relation to review of 
the reported PDs. The patients excluded with reference to the PD leading to exclusion will be 
listed and signed off in in the Pre-Analysis Review Form before DBL. 
The FAS is considered as the primary analysis population, and will be used for all primary 
and secondary efficacy analyses. The primary efficacy analysis will be repeated using the 
PPS. Any significant discrepancy between the results from the FAS and the PPS will be 
analysed and discussed. 
Secondary efficacy endpoints defined as to be analyzed after start of sunitinib will be based 
on the subset of subjects in FAS having at least one dose of sunitinib (or as described for 
PFS, when subjects were included according protocol versions prior to version 4.0). 
Baseline and safety will be presented using the safety set. 




Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
16 (30) 
 
 
 
The centrally assessed CT performed at the Sunitinib Start Visit is defined as 
CT baseline for evaluation of PFS, response rate and TTP after start of 
sunitinib in intermediate- and high-risk patients 
The Screening Visit is defined as baseline for all other assessments than 
those listed above. 
 
6.3.2 
Summary Statistics 
In general, data will be summarized by means of summary statistics. Continuous data will be 
presented with the number of observations, mean value, standard deviation, minimum, Q1, 
median, Q3 and maximum value. Categorical data will be presented as counts and 
percentages. All efficacy related variables will be summarized for the FAS population and all 
safety related data will be summarized for the safety population. 
 
For any assessments being evaluated by visit, an LOCF (Last observation carry forward) 
approach will be applied, where the last available information will be combined, 
independently of what the last recorded visit is. 
 
All descriptive statistics will be presented by stratum of high- and intermediate risk patients 
and pooled together and by treatment group. 
 
6.3.3 
Patient Data Listings 
Data collected in the CRF will generally be listed in Appendix 16.2 (see section 0). CRF 
check questions [e.g. Lab samples taken (Yes/No)] and reminders will not always be listed. 
Listings will be sorted by treatment group, study centre and patient number, or by patient 
number and treatment group. 
In CRF modules where a date is recorded, the date and the relative day may be included in 
the corresponding listing. In modules where both a start date and stop date are recorded, the 
duration may be included in the listing. 
 
6.3.4 
Demographic and Other Baseline Characteristics 
Patient disposition and discontinuation, Demographics (Age, Sex and Race) and other 
baseline characteristics (Weight and Height) and Medical History (mRCC): Duration of 
mRCC, Primary Tumor Stage, mRCC Symptoms and Severity Grade, Karnofsky 
Performance Status and other Medical history will be presented using summary statistics by 
treatment group and by intermediate/high risk stratum. The patient disposition and 
discontinuation will be based on all screened patients, while the other will be summarised for 
the Safety population. 
 
6.3.5 
Primary Efficacy analysis 
 
This is a descriptive proof of concept study and the sample size is not determined based on 
a statistical power calculation. Even though the trial is descriptive, some exploratory 
statistical testing will be conducted for primary endpoint, as described below. 
 
 
Overall Survival 
The primary endpoint is median OS, where OS is defined as the time from randomization to 
the time of death from any cause. 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
17 (30) 
 
 
 
Median OS after randomization in high-risk and intermediate-risk mRCC patients will be 
calculated and compared overall and by subgroup based on FAS in the following way: 
After the last patient has completed the trial, a collection of survival status, for patients still 
alive when exiting the study will be conducted by 
Drug Safety. Additional collections will 
be conducted up to 5 years after collection of the last patient’s 18 months survival data. For 
patients who die before end of trial, or patients with a known date of death during the 
additional collection, the survival time will be calculated as the difference in date of death and 
randomization date plus 1 day. Patients still alive at last contact, either during the trial or at 
the additional collection, will be censored at last date patient is known alive. Patients that are 
lost to follow-up during trial, or alive at end of trial where no follow-up information is available 
will be censored at last date patient is known alive. 
Survival functions will be displayed graphically using Kaplan-Meier plots, and life table 
statistics will be produced including summaries of number of events and censored 
observations. Estimates of 25%, 50% (median) and 75% percentiles of time of survival with 
corresponding 95% confidence intervals will be calculated. Addtionally, analyses where the 
survival functions will be compared between Intuvax+sunitinib, vs. sunitinib alone will be 
conducted using a stratified log-rank test, controlling for strata (high/intermediate-risk 
patients). 
The analyses will be done overall, and separately for high/intermediate risk group of patients. 
In addition, the primary efficacy endpoint will be evaluated using the PPS. 
The analyses will be conducted using Proc Lifetest, SAS®. 
 
18-month survival rate 
18-month survival rate is defined as the proportion of patients alive 18 months after 
randomization, or probability of surviving beond 18 months after randomization. 
The 18-month survival rates will be obtained using the same analyses as applied for OS, 
described above, where the fixed time point estimate, 18-months survival, will be estimated 
using the kaplan meier estimates as obtained above. The Timelist option in Proc Lifetest will 
be applied to get the estimated proportions at 18 months. Treatment groups will be 
compared using a z-test based on the proportions, where the Greenwood formula will be 
used for caculation of related standard errors. The analysis will be done overall, and 
separately for high/intermediate risk group of patients. Results will be presented including the 
estimated proportions with corresponding 95% CIs and the p-value for treatment difference. 
As the log-rank test for comparison between treatment groups is assessed on the full survival 
functions, as applied above, while the 18 months survival only utilize a subset of the compete 
survival data, the results from the treatment comparison based on the latter should be 
considered with caution. 
The endpoint will be evaluated for FAS as the main analysis, although will also be repeated 
for the PPS population. 
 
6.3.6 
Secondary Efficacy Analyses 
 
PFS from start of sunitinib according to RECIST 1.1 
PFS from start of sunitinib treatment will be derived as date whichever occurred first of any 
cause of death or date for first tumor progression (which is date for centrally assessed CT 
performed, according to RECIST 1.1) minus date for start of sunitinib treatment plus 1 day. 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
18 (30) 
 
 
 
For the analysis of PFS only deaths occuring before end-of-trial will be accounted for in the 
analysis. 
Analysis of PFS will be evaluated the following way: 
Survival functions will be displayed graphically using Kaplan-Meier plots, and life table 
statistics will be produced including summaries of number of events and censored 
observations. Estimates of cumulative 25%, 50% (median) and 75% percentiles of survival 
with corresponding 95% confidence intervals will be calculated. 
Comparison between Intuvax+sunitinib, vs. sunitinib alone will be done using a stratified log- 
rank test (controlling for strata intermediate/high risk), separte analyses will also be done by 
strata. 
With protocol versions before version 4.0, intermediate risk patients did not have to initiate 
treatment with sunitinib at a fixed time point according to the visit schedule. Consequently 
some patients were never started on sunitinib, and in some cases sunitinib treatment was 
initiated at a later time point. The sunitinib start date constitutes the baseline time point for 
PFS according to protocol version 4.0 and after. In the analyses, patients who either had a 
delay or never started sunitnib will be included under the assumption that sunitinib treatment 
would have been initiated according to the final design, the date of the visit following the 
nephrectomy visit will be used as baseline. 
Another issue that will be considered in the analysis is that some patients may have been 
discontinued based on general clinical disease progression as evaluated by investigator from 
symptoms/signs of disease, rather than based on a PD according to RECIST 1.1. For the 
analysis such cases will be handled strictly based on the RECIST 1.1 evaluation, thus if a 
patient is withdrawn without a CT confirmed PD the subject will be censored at last CT 
Analyses will be based on FAS and repeated for separately by strata.. 
 
 
Proportion of Objective Response Rate (ORR) and Disease Control Rate (DCR) from start of 
sunitinib 
Proportion of ORR from start of sunitinib treatment will be derived as the proportion of 
patients with the individual’s best overall response scored as “CR” or “PR” (using RECIST 
1.1) across all time points from first visit six (6) weeks after sunitib treatment, to end-of-study 
visit. Similarly, DCR will be derived as proportion of patients with best overall response 
scored as “CR”, “PR” or “SD”. 
ORR and DCR will be summarised and comparision of treatment groups will be made using 
the Cochran Mantel-Haenzel test, adjusting for strata. 
Duration of response will be derived only for patients meeting the ORR definition CR or PR, 
at least once, as the date of the first occurrence of PD or death minus the date at which the 
CR or PR was first observed, plus 1 day. Patients without an occurrence of a PD or death 
after CR of PR will contribute with the time up till last last tumor assessment. Data will be 
summarised descriptively. 
Duration of clinical benefit will be derived only for patients meeting the DCR definition CR, 
PR or SD at least once, as the date of the first occurrence of PD or death minus the date at 
which the CR, PR or SD was first observed, plus 1 day. Patients without an occurrence of a 
PD or death after CR, PR or SD will contribute with the time up till last last tumor 
assessment. Data will be summarised descriptively. 
The duration of stable disease is calculated for only those patients who exhibited a best 
response of stable disease response and will be calculated as the date for the first SD 








Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
22 (30) 
 
 
 
Sunitinib dose density will be derived as the total recorded dose during the time leading to 
event or censoring divided by the corresponding time period. 
 
These analyses will be conducted for evaluation of primary endpoint and PFS and in addition 
summary statistics for dose density will be provided split by treatment group and best 
response rate, ORR and DCR. 
 
6.3.8 
Exposure to Treatment 
All details collected in relation to the Intuvax vaccination will be listed and tabulated. 
Nephrectomy data will be listed. Exposure data for sunitinib use will be listed by treatment 
group and by high/intermediate risk stratum. Duration of sunitinib treatment will be 
summarised by treatment group and strata. Patient sunitinib compliance will be evaluated 
summarising the number of dispensed tablets minus the number of returned and lost tablets. 
 
6.3.9 
Concomitant Medications 
All concomitant medications/therapies will be summarised as number of patients being 
treated with each type of medication/therapy classified according to ATC level 3 group text 
and World Health Organization (WHO) Drug Dictionary preferred name. 
Prior medication/therapy is defined as medication/therapy administered prior to Screening 
Visit. All medication/therapy administered after Screening Visit are considered concomitant 
medication/therapy. Prior medication/therapy will be indicated as past or ongoing at 
Screening. 
In summary tables, each patient is only counted once for each drug, on a preferred name 
level and will be classified according to the first start date of the medication. If there is an 
occurrence of the same preferred name before and after screening, the medication is only 
counted as started before screening. For total within each group text, a patient can be 
counted both before and after screening if one medication is present at screening, and 
another medication with another preferred name starts after baseline. 
 
6.3.10 
Adverse Events 
Analyses of AEs will be based on the Safety set. AEs will be coded using Medical Dictionary 
for Regulatory Activities (MedDRA) Version 17.1. 
All AEs will be listed by treatment group, with patient number in addition to type of event 
(verbatim term, system organ class and preferred term), start and stop day relative to first 
dose of treatment, seriousness, intensity, action taken, relationship to study drug and 
outcome of AE. Treatment-emergent status will be flagged in the listing. In addition, 
corresponding listings of screening AEs, serious AEs (SAEs), AEs leading to discontinuation 
of study medication, AEs leading to death will be produced. 
The total number of AEs will be summarized including the number of patients with at least 
one AE, the total number of AEs, the number of unique AEs, by seriousness, intensity, 
action taken, relationship to study drug and by treatment group and in total. The number of 
AEs per severity (CTCAE) and relation to trial drug will also be included and summarized per 
treatment group and in total. SAEs will also be summarized separately in a similar manner. 
The number of patients and the number of AEs will be tabulated by MedDRA system organ 
class (SOC) and preferred term in descending order of overall frequency. 
AEs occurring during the 4 hours following the Intuvax vaccination will in addition be 
summarized separately. 
Summary statistics of AE will be done by treatment group. 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
23 (30) 
 
 
 
Pre treatment events occurring between first assessment at Screening and first Intuvax dose 
(for vaccinated patients) and between first assessment at Screening and Nephrectomy (for 
unvaccinated patients) will be summarized separately. 
 
6.3.11 
Other Safety Assessments 
 
Vital Signs 
For vital signs parameters (systolic and diastolic blood pressure, supine heart rate and 
temperature) summary statistics will be produced for observed values by visit. In addition, the 
difference from baseline to each visit at which they were assessed will be derived and 
presented. 
Vital signs assessed at time points post vaccination will be summarised separately. 
Clinical Laboratory Measurements 
The laboratory categories are Hematology, Clinical Chemistry, Coagulation, Urine analysis 
and Pregnancy analysis. 
For all laboratory parameters, summary statistics will be produced for observed values by 
visit. In addition, the difference from baseline to each visit at which they were assessed will 
be derived and presented. The number of abnormal (low and high) and clinically significant 
observations will be tabulated for each treatment group by visit. Abnormal values will be 
flagged in listings. 
Shift tables that show the number of patients who changed from low, normal or high at 
baseline to low, normal or high at each post-baseline time of assessment will be presented. 
Physical Examination 
Physical examination results will be tabulated including number of subjects with normal, 
abnormal not clinically significant or clinically significant abnormalities by visit. Corresponding 
shift tables for changes from baseline will be presented, and all the results will be listed. 
 
6.4 
Level of Significance, Multiple Comparisons and Multiplicity 
The sample size in this trial is not based on a formal power calculation. Any inferential 
statistical methods applied in this trial will be regarded as exploratory, therefore no 
adjustments will be applied to adjust for multiple testing. 
 
6.5 
Adjustment for Covariates 
Parametric analyses based on statistical models will not be conducted. For primary endpoint 
a stratified Log-rank test will be done including adjustment for high/intermediat risk strata. 
 
6.6 
Handling of Dropouts and Missing Data 
Primary and secondary efficacy endpoint 
The primary and secondary efficacy endpoint analysis will be conducted on available data 
(observed cases). Missing data due to loss of follow-up and rules for censoring will be done 
as described in each corresponding section. 
Handling of incomplete dates 
 
Incomplete (partial or missing) dates will be presented in data listings as provided on 
the eCRF. However, for use in calculations (e.g. to calculate the duration of an AE or 
medication use) dates will be estimated as follows. 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
24 (30) 
 
 
 
For partial start-dates 
• 
If the year is unknown, then the date will not be imputed and will be assigned a 
missing value 
• 
If the month is unknown, then: 
o If the year matches the year of the first dose date, then impute the month and 
day of the first dose date 
o Otherwise, assign ‘January’ 
• 
If the day is unknown, then: 
o If the month and year match the month and year of the first dose date, then 
impute the day of the first dose date. 
o Otherwise, assign ‘January’. 
 
For partial end-dates, 
• 
If the year is unknown, then the date will not be imputed and will be assigned a 
missing value. 
• 
If the month is unknown, then assign ‘December’. 
• 
If the day is unknown, then assign the last day of the month 
 
If the above rules for end-dates result in a date after the patient was ended the 
study, then the end date will be replaced with the patient’s date of 
completion/withdrawal. Furthermore, should the above rules not result in the most 
conservative date (as described below), then the imputed value may be replaced by 
a date that will lead to a more conservative analysis. 
 
After implementing the rules above, to determine whether AEs with incomplete start 
or stop dates are pre-treatment or treatment-emergent the following strategy will be 
used: 
• 
If the start date and stop date are both missing, the most conservative approach is 
taken and the AE is considered to be treatment-emergent 
• 
If the start date is missing but the stop date is not missing and is on or after the day of 
first study drug administration but before or on the Week 12 visit date then the most 
conservative approach is taken and the AE is considered to be treatment-emergent; 
• 
If the start date is missing but the stop date is not missing and is before the day of 
first study drug administration then the AE is considered to be pre-treatment. 
 
If the date of first and/or last dose of study drug administration is missing then 
duration of exposure will be set to missing. 
 
Handling of unscheduled visits 
 
Descriptive summaries and by-visit analyses will be presented according to the 
planned (scheduled) visits, unless otherwise specified. 
 
For patients withdrawing early, where discontinuation data is collected on the end-of- 
trial visit, the data will be reallocated to the visit nearest to withdrawal, if applicable. 
 
Any data collected on unscheduled visits, will be reallocated to the visit nearest in 
time to the planned visits where the corresponding information is not already 
available. This will be done by allocating the unscheduled data within the visit 
windows by corresponding visit as listed below. 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
25 (30) 
 
 
 
 
Vacc1 
from screening to 28 days 
Vacc2 
+/- 3 days 
 
 
 
 
 
Nephrectomy Visit: 
Sun-Start Visit: 
At least 3 days after Vacc2 Visit and within 
63 days from Screening Visit for patients 
randomized to Intuvax followed by 
sunitinib. Within 63 days from Screening 
Visit for patients randomized to sunitinib 
only. 
Five (5) to eight (8) weeks after 
Nephrectomy Visit 
SFU[6W]: 
6 weeks (±7 days) after Sun-Start Visit 
SFU[12W]: 
12 weeks (±7 days) after Sun-Start Visit 
SFU[24W]: 
24 weeks (±7 days) after Sun-Start Visit 
SFU[36W]: 
36 weeks (±7 days) after Sun-Start Visit 
SFU[48W]: 
48 weeks (±7 days) after Sun-Start Visit 
SFU[60W]: 
60 weeks (±7 days) after Sun-Start Visit 
End of Study Visit: 
78 ±2 weeks after Screening 
 
6.7 
Multicentre Studies 
Due to the limited number of patients included in this trial, site level summary statistics will 
not be produced. A summary of number of patients per country will be generated, and only if 
relevant additional descriptive statistics for primary and secondary endpoints by country may 
be produced if any treatment by country effects are suspected. 
 
6.8 
Examination of Subgroups 
In general be subgroup evaluations will performed in this study based on the stratification 
levels, high and intermediate risk patients. Statistical analyses will be performed on the 
primary endpoint of OS and proportion of 18-months survival and for the secondary endpoint 
of PFS. Analysis will be done for the FAS population. 
Also, analysis of subgroup of patients from the site in Gothenburg that performes 
embolisation the day before operation will be evaluated descriptively for all biopsy data and 
for corresponding patient characteristics and demographic characteristics. 
A summary overview of all Adverse Events, and summary of number of patients by AE 
intensity and relationship with treatment will be produced split by ilixadencel batch subgroup 
(INT and CCK). 
 
 
6.9 
Interim Analysis 
An interim analysis is not planned for in this study. 
 
6.10 
Data Monitoring 
Not applicable. 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
26 (30) 
 
 
 
7 
REFERENCES 
 
1. Heng DYC, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C et al. Prognostic 
factors for overall survival in patients with metastatic renal cell carcinoma treated with 
vascular endothelial growth factor–targeted agents: Results from a large, multicenter study. J 
Clin Oncol. 2009; 27(34):5794-99 
2. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET et al. Toxicity and 
response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 
5(6):649-55 
3. Marcello Pagano, Kimberlee Gauvreau. Principles of Biostatistics, 2nd edition, 2000. 
4. EORTC QLQ-C30 Scoring Manual, ISBN 2-9300 64-22-6, Third edition, 2001 
 
8 
APPENDIX 1 
 
Data from patients screened but not included in the study will not be presented in any listings 
or tables. 
 
8.1 
Tables to be Produced for the Clinical Study Report (Section 14 according to 
ICH E3) 
(Table numbers refer to section numbers in ICH E3) 
14.1 DEMOGRAPHIC DATA 
(Baseline presentations will be based on the safety set overall and split by stratum if not 
otherwise stated below) 
 
14.1.1 
Patient Disposition in Analysis Sets and Reason for Exclusions (All included patients) 
14.1.2 
Patient Discontinuation (All included patients) 
14.1.3 
Number of Patients by Visit (Safety Set) 
14.1.4 
Demograph cs: Age, Sex and Race (Safety Set) 
14.1.5 
Number of Patients by Country (Safety Set) 
14.1.6 
Other Baseline Characteristics: Weight, Height (Safety Set) 
14.1.7 
Karnofsky Performance Status (Safety Set) 
14.1.8 
Med ca  H story (mRCC): Durat on of mRCC, TNM Stage, mRCC Symptoms and Sever ty 
Grade (Safety Set) 
14.1.9 
Med ca  and Surg ca  H story (Exc ud ng mRCC) (Safety Set) 
 
14.2 EFFICACY DATA 
(Efficacy presentations will be split by stratum, all presentation will be based on FAS if not 
otherwise stated below) 
Tables 
14.2.1 
Life table statistics of OS by treatment group (FAS, PPS and Subgroups) 
14.2.2 
Quartile Estimates (Median) and Confidence Intervals for OS (FAS, PPS and Subgroups) 
14.2.3 
Log rank test compare survival functions for treatments groups OS (FAS, PPS and 
Subgroups) 
14.2.4 
The estimates of the second primary endpoint of the proportion of 18-months survival 
and corresponding z-test test. (FAS, PPS and Subgroup) 




Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
28 (30) 
 
 
 
14.2.38 
 
14.2.39 
 
 
Figures 
14.2.35 
Kaplan-Meier plots OS survival functions by treatment group (FAS, PPS, Subgroups) 
14.2.36 
Kaplan-Meier plots PFS survival functions by treatment group (FAS, PPS, Subgroups) 
14.2.37 
Kaplan-Meier plots TTP survival functions by treatment group (FAS, Subgroups) 
14.2.38 
Kaplan-Meier plots TTF survival functions by treatment group (FAS, Subgroups) 
14.2.39 
Waterfall charts over the response distribution (FAS and Subgroups) 
14.2.40 
Swimmer plots time from screening (FAS and Subgroups) 
14.2.41 
Swimmer plots time from randomization (FAS and Subgroups) 
14.2.42 
Plot over mismatch patient/donor and CD8+ T-cells (as analysed by 
) and 
corresponding Spearman correlation (FAS and Subgroups) 
14.2.43 
Plot over mismatch patient/donor and CD8+ T-cells (as analysed by 
) and 
corresponding Spearman correlation (FAS and Subgroups) 
 
 
14.3 SAFETY DATA 
(Safety presentations will be based on the safety set unless otherwise stated below) 
 
14.3.1 Displays of Adverse Events 
14.3.1.1 
Summary of Adverse Events 
14.3.1.2 
Summary of Adverse Events by ilixadencel batch subgroup 
14.3.1.3 
Adverse Events by System Organ Class and Preferred term 
14.3.1.4 
Adverse Events: Number of Patients by Intensity and Relationship by Treatment 
 
14.3.1.5 
Adverse Events: Number of Patients by Intensity and Relationship by Treatment by 
ilixadencel batch subgroup 
14.3.1.6 
Serious Adverse Events by System Organ Class and Preferred term 
14.3.1.7 
Related Adverse Events by System Organ Class and Preferred term 
14.3.1.8 
Adverse Events by CTCAE grade and System Organ C ass and Preferred term 
14.3.1.9 
Adverse Events occurring 4 hours following the Intuvax vaccination 
14.3.1.10 
Adverse Events occurring between first assessment at Screening and first Intuvax dose 
14.3.1.11 
Adverse Events occurring between first assessment at Screening and Nephrectomy 
14.2.1.12 Related Serious Adverse Events by System Organ Class and Preferred term 
 
14.3.2 Listings of Deaths, Other Serious Adverse Events, and Other Significant Adverse 
Events 
14.3.2.1 
Listings of Deaths, Other Serious Adverse Events, and Other Significant Adverse Events 
 
14.3.4 Abnormal Laboratory Value Listings 
14.3.4.1 
Abnormal Laboratory Value Listing 
14.3.4.2 
Other Relevant Laboratory Analyses 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
29 (30) 
 
 
 
14.3.4.3 
Summary Statistics by Visit/Timepoint with Difference from Baseline (including the 
number of abnormal (low and high) and clinically significant observations) 
14.3.4.4 
Shift Tables 
 
14.3.5 Extent of Exposure 
14.3.5.1 
Exposure vaccination 
14.3.5.2 
Exposure sunitinib and sunitinib dose density 
 
14.3.6 Vital Signs 
14.3.6.1 
Summary Statistics with Difference from Baseline for Vital Signs (Systolic Blood Pressure, 
Diastolic Blood Pressure, Heart Rate and weight) 
14.3.6.2 
Vital signs post vaccination 
 
14.3.7 Physical Examination 
14.3.7.1 
Summary of Physical Examination 
14.3.7.2 
Shift Tables for Physical Examination 
 
14.3.8 ECG 
14.3.8.1 
Summary of ECG 
 
 
14.3.9 Concomitant Medication and Therapy 
14.3.8.2 
Summary of Concomitant Medication 
14.3.8.3 
Summary of Sunitinib doses 


Statistical Analysis Plan 
Version: Final 1.0 
Date: 2019-06-19 
Sponsor: Immunicum AB 
Study Code: IM-201 
EudraCT No.: 2014-004510-28 
ST_Temp ate_Stat st ca  Ana ys s P an_04 
30 (30) 
 
 
 
 
8.2 
Listings of Individual Patient Data and Other Information to be Produced for 
the Clinical Study Report (Sections 16.1 and 16.2 in ICH E3) 
(Listing numbers refer to the relevant appendix number in ICH E3. CRF check 
questions/reminders will not be listed.) 
16.1.7 
Randomization Scheme 
16.2.1.1 
Discontinued Patients, Reason for Discontinuation 
16.2.1.2 
Visit Dates and Other Important Dates 
16.2.1.3 
Study Termination 
Patients Excluded from the Efficacy Analysis (Evaluability, Reason for Evaluability 
16.2.3.1 
Classification) 
16.2.3.2 
Treatment Allocation and Evaluability for All Patients 
16.2.4.1 
Demographic Data 
16.2.4.2 
Medical History 
16.2.4.3 
Inclusion Criteria Not Met and Exclusion Criteria Met 
16.2.4.4 
Existing Symptoms 
16.2.4.5 
CT/ MRI-scan 
16.2.4.6 
HLA tissue-typing 
16.2.4.7 
Karnofsky 
16.2.4.8 
Heng / Randomization 
16.2.4.9 
General information 
16.2.5.1 
Compliance and/or Drug Concentration Data vaccine 
16.2.5.2 
Compliance and/or Drug Concentration Data sunitinib 
16.2.6.1 
RECIST 1.1 eva uat on 
16.2.6.2 
Eff cacy parameters (ORR, OS, PFS, TTP, TTF) 
16.2.6.3 
 
16.2.6.4 
ECOG 
16.2.7.1 
Adverse Event Listings by Treatment, Patient, Relative Day or Week. (Since 
demographic data and IMP are listed in separate listings, this listing will only contain 
information on adverse events, for space reasons.) 
16.2.7.3 
Adverse Event Listings by System Organ Class, Preferred Term, Treatment and Patient 
16.2.7.4 
Pre-treatment Adverse Event Listings by System Organ Class, Preferred Term, 
Treatment and Patient 
16.2.8.1 
Listing of Individual Laboratory Measurements by Patient 
16.2.8.2 
Listing of Relevant Comments Regarding Laboratory Values 
16.2.8.3 
Serology 
16.2.8.4 
Pregnancy 
16.2.9.1 
V ta  S gns 
16.2.9.1 
Physical Examination 
16.2.10.1 ECG 
16.2.11.1 Concomitant Medications and Therapy 
16.2.12.1 Alloimmunization 
16.2.13.1 Surgery-Nephrectomy 
16.2.14.1 Immunohistology