This study was conducted in order to evaluate the efficacy and safety of the cancer vaccine IMA901 and GM-CSF as adjuvant in the treatment of advanced renal cell carcinoma.

Patients received vaccination with GM-CSF followed by IMA901 during the study period of 9 months. Patients received pre-treatment with a single i.v. infusion of cyclophosphamide prior to the first vaccination.

This is a multicenter, open label, randomized phase 2 study which investigated the effect of a second-line systemic treatment with IMA901 plus GM-CSF in RCC patients. Randomization was done according to a pre-treatment with low-dose cyclophosphamide (CY). Secondary endpoints comprised tumor response parameters.

The study population consisted of HLA-A*02-positive men or women with advanced RCC of the clear-cell type classified as having a favorable or intermediate risk after first-line systemic therapy for. Patients had to be aged 18 years or older, had at least have one measurable tumor lesion and had have received first-line tyrosine kinase inhibitor or cytokine systemic therapy for advanced disease, during or after which the patient had experienced disease progression.

Patients in both arms received a total of 17 vaccinations with GM-CSF followed by IMA901 during the 9 month treatment period.

At screening baseline tumor status was assessed by CT or MRI. During the study tumor assessments were performed every 6 weeks.

Immunomonitoring (T-cell responses to peptides contained in IMA901 and analysis of other immune cell populations that may influence T-cell responses), serum levels of antibodies and molecules with suspected influence on immune response were assessed on several occasions during the study.

Safety assessment comprised continuous adverse event reporting, regular physical examinations and regular assessments of vital signs, hematology, blood chemistry and urine. A 12-lead ECG was performed at screening and at the end of the study. Pregnancy testing was performed according to applicable legislation in the country where the trial was performed. At the very least, women of childbearing potential had have to undergo a pregnancy test during screening for the study, before the first dose was applied and at the end of the study.

Inclusion Criteria:

• Aged at least 18 years
• HLA type: HLA-A*02-positive
• Histologically documented advanced clear-cell RCC
• Patients who have received first-line tyrosine kinase inhibitor or cytokine systemic therapy for advanced disease systematic therapy for advanced disease and must be candidates for second-line therapy (NOTE: in Germany and Austria only patients after first-line tyrosine kinase inhibitor failure will be included into the study)
• Patients having experienced documented tumor progression
• At least one unidimensional measurable target lesion
• Karnofsky Performance Status ≥ 80%
• Favorable or intermediate risk according to the 3-score MSKCC criteria.
• Able to understand the nature of the study and give written informed consent
• Willingness and ability to comply with the study protocol for the duration of the study

Exclusion Criteria:

• Poor risk according to the 3-score MSKCC criteria

• Immunosuppressive therapy within 4 weeks before study entry, e.g. corticosteroid treatment

• History of other malignant tumors, except non-melanoma-skin cancer or curatively excised cervical carcinoma in situ

• Presence of brain metastases on MRI or CT scan

• Patients with a history or evidence of systemic autoimmune disease

• Any vaccination in the two weeks before study entry

• Any planned prophylactic vaccination from study entry until the end of the induction period (5 weeks after the first vaccination)

• Known active hepatitis B or C infection

• Known HIV infection

• Any other infection with a biological agent that can cause a severe disease and poses a severe danger to lab personnel working on patient tissues.

• Any of the following in the 4 weeks before study entry:

  1. Major surgery
  2. Anticancer treatments including (but not limited to) cytotoxic chemotherapy, radiotherapy, immunotherapy, hormone therapy, tyrosine kinase inhibitors, monoclonal antibodies
  3. Unresolved toxicity from prior anticancer treatments including (but not limited to) cytotoxic chemotherapy, hormone therapy, tyrosine kinase inhibitors, monoclonal antibodies, radiotherapy, or immunotherapy
  4. Received study drug within any clinical study

• Any of the following abnormal laboratory values:

  1. Hematology: Hb < 9 g/dL; WBC < 3 x 109/L; neutrophils < 1.5 x 109/L; lymphocytes < 1.0 x 109/L; platelets < 100 x 109/L
  2. Liver function: serum bilirubin > 1.5 x upper normal limit (unless a history of Gilbert's disease); ALAT or ASAT > 3 x upper normal limit (>5 x upper normal limit if liver metastases are present)
  3. Renal function: serum creatinine > 200 µmol/L

• Patients with other significant diseases currently uncontrolled by treatment which might interfere with study completion, for example:

  1. Heart failure or non compensated active heart disease
  2. Severe coronary heart disease, cardiac arrhythmia requiring medication, or uncontrolled hypertension
  3. Symptomatic neurotoxicity (motor or sensory) ≥ grade 2 National Cancer Institute - Common Toxicity Criteria (NCI-CTC).
  4. Severe pulmonary dysfunction

• Psychiatric disabilities, seizures or central nervous system disorders that may interfere with the ability to give informed consent or perform adequate follow-up in the investigator's opinion

• Active infections requiring oral or intravenous antibiotics

• Women or men who decline to practice a medically approved method of contraception

• Pregnancy or breastfeeding

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