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

I

Immatics

Status and phase

Completed
Phase 3

Conditions

Metastatic Renal Cell Carcinoma

Treatments

Drug: IMA901
Drug: Sunitinib
Drug: Cyclophosphamide
Biological: GM-CSF

Study type

Interventional

Funder types

Industry

Identifiers

NCT01265901
2010-022459-45 (EudraCT Number)
IMA901-301

Details and patient eligibility

About

The primary objective of the phase III study is to investigate whether IMA901 can prolong overall survival in patients with metastatic and/or locally advanced renal cell carcinoma (RCC) when added to standard first-line therapy with sunitinib.

Secondary objectives include a subgroup analysis of overall survival in patients defined by a certain biomarker signature, the investigation of progression-free survival, best tumor response, safety, and immunological parameters.

Full description

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.

Enrollment

339 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

339 participants in 2 patient groups

Sunitinib
Active Comparator group
Description:
Sunitib as Standard therapy per Label.
Treatment:
Drug: Sunitinib
IMA901 plus GM-CSF added to sunitinib after single dose of cy
Experimental group
Description:
After 1 cycle of sunitinib, intradermal vaccinations with IMA901 plus GM-CSF as adjuvant after a single dose of cyclophosphamide will be applied for a period of 4 months while continuing treatment with sunitinib
Treatment:
Biological: GM-CSF
Drug: Cyclophosphamide
Drug: Sunitinib
Drug: IMA901

Trial contacts and locations

106

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Data sourced from clinicaltrials.gov

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