Intratumoral Vaccination With Intuvax Pre-nephrectomy Followed by Sunitinib Post-nephrectomy vs Sunitinib Post-nephrectomy in Newly Diagnosed Metastatic Renal Cell Carcinoma (mRCC)

Patients, all planned for nephrectomy, will be stratified according to the Heng risk criteria
(36 high risk patients, 54 intermediate risk patients) and randomized in a 2:1 ratio to
receive Intuvax+ Sunitinib or Sunitinib alone.

Two doses of Intuvax 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 AB
to further investigate the possibility of exploiting Intuvax vaccination when combined with
Sunitinib for the treatment of mRCC patients.

Inclusion Criteria:

1. Newly (<6 months) diagnosed RCC (histological/cytological verification is optional)
with at least one (1) CT-verified metastasis ≥10mm 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 5-8 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 x10e9/L

- B-Platelet count ≥150 x10e9/L

- B-Hemoglobin ≥90 g/L

8. S-creatinine and S-bilirubin ≤ 1.5 x ULN. S-ALAT and S-ASAT ≤ 2.5 x 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]) Female of childbearing potential must have a negative from
Screening until 90 days after last dose of INTUVAX and/or until completed sunitinib
treatment whichever occurs later.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

2. CNS metastasis that is symptomatic or progressing or untretaed 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, systemic lupus erythematosus (SLE),
vasculitis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, and other
rheumatological diseases

4. Treatment with per oral systemic corticosteroids exceeding 10mg/day within seven (7)
days before Screening until nephrectomy (inhaled, intranasal and local steroids
accepted irrespective of dose)

5. Known cardiomyopathy and/or clinical significant abnormal ECG findings at Screening
disqualifying the patient from nephrectomy and from subsequent sunitinib treatment

6. 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 before 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, hepatitis B and hepatitis C)

15. ECOG performance status >2 after optimization of analgesics

16. Abnormal and clinical significant coagulation parameters at the discretion of the
Investigator, i.e.:

- Prothrombin Time - International Normalized Ratio (PT-INR)

- Activated Partial Thromboplastin Time (APTT) patients beeing treated with
anticoagulants are excluded if teh 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 sunitinib or to chemically related products or
likely to be exacerbated to by any component of the study products

19. Prior systemic antitumour therapy within 28 days before Screening Visit. However,
local radiation therapy to any area except for the abdominal/retroperitoneal area
including the kidney tumour 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