IMA901 in Patients Receiving Sunitinib for Advanced/Metastatic Renal Cell Carcinoma

This is a multicenter, open-label, randomized phase III study to investigate whether
therapeutic vaccination with IMA901, a mult-peptide cancer vaccine (TUMAP), can prolong
overall survival in patients with metastatic and/or locally advanced RCC when added to
standard first-line therapy with sunitinib (primary endpoint).

Secondary endpoints include a subgroup analysis of overall survival in patients who are
positive for a prospectively defined primary biomarker signature (identified as being
predictive for improved clinical outcome in IMA901-vaccinated patients in the previous phase
II study), progression-free survival (PFS), best overall response, cellular immunomonitoring
in a subset of patients, and safety. Safety analysis will be based on adverse events (AEs),
physical examinations, vital signs, hematology, clinical chemistry, urinalysis and ECG
changes.

Further endpoints include subgroup analyses of overall survival in patients who are positive
for further prospectively defined biomarkers (identified in the previous phase II study), and
exploratory screening of new biomarkers (to be investigated in patients' blood and paraffin
sections from tumor tissue) to predict better clinical outcome as response to vaccination
with IMA901. Biomarker sets will not be used for patient selection in this study.

Inclusion Criteria:

1. Aged at least 18 years.

2. HLA type: HLA-A*02-positive

3. Metastatic and/or locally advanced RCC with clear cell histology (histological
confirmation by local pathologist required). NOTE: prior nephrectomy is NOT required.

4. Measurable and/or non-measurable tumor lesions as per RECIST 1.1

5. Patients who are candidates for a first-line therapy with sunitinib.

6. Favorable or intermediate risk according to the 6-score risk criteria in patients
treated with VEGF-targeted agents according to Heng [Heng et al. 2009]. The patient
has a favorable risk if none, or intermediate risk if one or two of the following
criteria apply (if three or more criteria apply the patient is not eligible):

1. Hemoglobin < LLN,

2. Serum corrected calcium > ULN,

3. Karnofsky performance status < 80%,

4. Time from initial diagnosis to initiation of therapy < 1 year,

5. Absolute neutrophil count > ULN,

6. Platelets > ULN.

7. Able to understand the nature of the study and give written informed consent.

8. Willingness and ability to comply with the study protocol for the duration of the
study.

9. Female patients who are post menopausal (no menstrual period for a minimum of 1 year),
or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or
hysterectomy) or practice a medically acceptable method of birth control.

10. Male patients willing to use contraception (upon study entry and during the course of
the study or have undergone vasectomy.

Exclusion Criteria:

1. Prior systemic therapy for metastatic disease. (Note: prior adjuvant treatment for
non-metastatic disease is allowed, however adjuvant therapy must have been stopped ≥ 1
year before Visit C).

2. History of or current brain metastases.

3. Abnormal ≥ CTC Grade 3 laboratory values for hematology (Hb, WBC, neutrophils,
lymphocytes, platelets), liver (serum bilirubin, ALAT or ASAT) and renal function
(serum creatinine).

4. Metastatic second malignancy.

5. Localized second malignancy expected to influence the patient's life span.

6. Patients with a history or evidence of systemic autoimmune disease, e.g., rheumatoid
arthritis, multiple sclerosis, systemic lupus erythematodes (SLE), scleroderma,
Sjögren's syndrome, Wegener's granulomatosis, Guillain-Barre syndrome.

7. Known active hepatitis B or C infection.

8. Known HIV infection.

9. Active infections requiring oral or intravenous antibiotics.

10. Any other known infection with a biological agent that can cause a severe disease and
poses a severe danger to lab personnel working on patients' blood or tissue.

11. Received study drug within any clinical study (including approved and experimental
drugs) within 4 weeks before sunitinib start.

12. Serious intercurrent illness, which according to the investigator, poses an undue risk
for the patient when participating in the trial, including, but not limited to, any of
the following:

- Clinically significant cardiovascular disease (e.g., uncontrolled hypertension;
clinically significant cardiac arrhythmia, clinically significant
QT-prolongation),

- New York Heart Association class III-IV congestive heart failure,

- Symptomatic peripheral vascular disease,

- Severe pulmonary dysfunction,

- Psychiatric illness or social situation that would preclude study compliance.

13. Less than 12 months since any of the following:

- Myocardial infarction,

- Severe or unstable angina,

- Coronary or peripheral artery bypass graft,

- Cerebrovascular event incl. transient ischemic attack,

- Pulmonary embolism / deep vein thrombosis (DVT).

14. Pregnancy or breastfeeding.

15. Any condition which in the judgment of the investigator would place the patient at
undue risk or interfere with the results of the study.