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

A Randomized, Controlled Phase III Study Investigating IMA901 Multipeptide Cancer Vaccine in Patients Receiving Sunitinib as First-line Therapy for Advanced/Metastatic Renal Cell Carcinoma

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Renal Cell Carcinoma
• Intervention / Treatment: Drug: Sunitinib; Biological: GM-CSF; Drug: Cyclophosphamide; Drug: IMA901

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 339
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Bordeaux, France, 33075
    • Hopital Saint André
  • Caen Cedex, France, 14076
    • Centre Francois Baclesse, Comite Urologie-Gynecologie
  • Clermont Ferrand Cedex, France, 63003
    • CHU Estaing, Service d'hematologie clinique adulte et de therapie cellulaire
  • Paris, France, 75015
    • Hospital Européen Georges Pompidou, Service d'oncologie medicale
  • Saint-Herblain, France, 44800
    • Centre Rene Gauducheau, Service d'oncologie medicale
• Germany
  • Berlin, Germany, 12200
    • Universitätsmedizin Berlin, Charité Campus Benjamin Franklin, Urologische Klinik und Hochschulambulanz
  • Bochum, Germany, 44791
    • Klinik für Hämatologie und internistische Onkologie, Augusta-Krankenanstalt gGmbH
  • Bonn, Germany, 53127
    • Medizinische Klinik III für Hämatologie und Onkologie, Universitätsklinikum Bonn
  • Essen, Germany, 45122
    • Universitätsklinikum Essen, Klinik für Innere Medizin (Tumorforschung)
  • Hannover, Germany, 30625
    • Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69120
    • Nationales Centrum für Tumorerkrankungen (NCT), Medizinische Onkologie
  • Leipzig, Germany, 04103
    • Klinik und Poliklinik für Urologie, Abteilung für Operative Medizin, Universitätsklinikum Leipzig
  • Munich, Germany, 81675
    • Klinikum rechts der Isar, Urologischen Klinik und Poliklinik, Technische Universität München
  • Planegg, Germany, 82152
    • Urologische Klinik Dr. Castringius, München-Planegg
  • Straubing, Germany, 94315
    • Klinikum St. Elisabeth Straubing GmbH
  • Tübingen, Germany, 72076
    • Klinik für Urologie, Universitätsklinikum Tübingen
  • Ulm, Germany, 89081
    • Klinik für Innere Medizin III, Hämatologie - Onkologie - Rheumatologie - Infektionskrankheiten, Universitätsklinikum Ulm
  • Villingen-Schwenningen, Germany, 78052
    • Schwarzwald-Baar Klinikum Villingen-Schwenningen, Abteilung Hämatologie und Onkologie
• Hungary
  • Budapest, Hungary, 1076
    • Péterfy Utcai Hospital, Urology department
  • Budapest, Hungary, 1082
    • Semmelweis University, Urology Clinic
  • Budapest, Hungary, 1106
    • Urology Department, Bajcsy-Zsilinszky Hospital
  • Budapest, Hungary, 1145
    • Uzsoki Utcai Hospital, Oncoradiology Center
  • Debrecen, Hungary, 4032
    • University of Debrecen, Faculty of Medicine, Institute of Oncology
  • Debrecen, Hungary, 4032
    • University of Debrecen, Faculty of Medicine, Urology Clinic
  • Debrecen, Hungary, 4043
    • Kenézy Hospital, Urology Department
  • Eger, Hungary, 3300
    • Oncology Centre, Markhot Ferenc Training Hospital and Clinic
  • Gyula, Hungary, 5700
    • Pándy Kálmán County Hospital, Oncology and Radiotherapy Center
  • Miskolc, Hungary, 3526
    • Urology department, BAZ County Hospital
  • Pécs, Hungary, 7621
    • Urology Clinic, University of Pécs
  • Szeged, Hungary, 6720
    • Oncology Therapy Clinic, University of Szeged
  • Szolnok, Hungary, 5000
    • County Oncology Centre, Hetényi Géza Hospital
  • Zalaegerszeg, Hungary, 8900
    • Oncology Department, Zala County Hospital
• Italy
  • Arezzo, Italy, 52100
    • Presidio Ospedaliero Ospedale San Donato, U.O. Oncologia Medica
  • Aviano, Italy, 33081
    • Centro di Riferimento Oncologico di Aviano
  • Bologna, Italy, 40138
    • Medical Oncology Unit, Policlinico Sant'Orsola Malpighi
  • Modena, Italy, 41100
    • Department of Oncology and Haematology, Division of Medical Oncology, University of Modena and Reggio Emilia
  • Pavia, Italy, 27100
    • Dipartimento di Oncologia, IRCCS Fondazione
  • Reggio Emilia, Italy, 42100
    • Medical Oncology, Hospital Santa Maria Nuova of Reggio Emilia
  • Rimini, Italy, 47923
    • Oncologia Medica, "Ospedale Infermi"
  • Sassari, Italy, 07100
    • Ospedale S.S Annunziata Sasari
  • Torino, Italy, 10060
    • IRCC-Istituto di Ricerca e Cura del Cancro
• Netherlands
  • Nijmegen, Netherlands, 6525
    • University Medical Center St. Radboud Centraal, Department of Urology
• Norway
  • Oslo, Norway, 0310
    • University Hospital, UOS - Radiumhospital
• Poland
  • Białystok, Poland, 15-027
    • Białostockie Centrum Onkologii
  • Bydgoszcz, Poland, 85-796
    • Prof. Franciszek Łukaszczyk Oncology Center
  • Dobra, Poland, 72-003
    • Pomeranian Medical University Hospital, NZOZ Innowacyjna Medycyna
  • Elbląg, Poland, 82-300
    • Wojewódzki Szpital Zespolony, Oncology Department
  • Gdańsk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne, Klinika Urologii
  • Lublin, Poland, 20-090
    • Chemotherapy Department Center of Oncology of the Lublin Region
  • Olsztyn, Poland, 10-513
    • Olsztyński Oncology Center "KOPERNIK"
  • Poznań, Poland, 60-569
    • Przemienienia Pańskiego Clinical Hospital no. 1, Oncology Clinic
  • Rzeszów, Poland, 35-242
    • Private Outpatient Clinic MRUKMED
  • Szczecin, Poland, 70-111
    • Samodzielny Publiczny Szpital Kliniczny Nr 2 PUM w Szczecinie
  • Warsaw, Poland, 02-005
    • Dzieciątka Jezus Clinical Hospital of Medical University, General Urology and Oncology Clinic
  • Warsaw, Poland, 04-125
    • Niepubliczny Zaklad Opieki Zdrowotnej "Magodent"
  • Warsaw, Poland, 50-566
    • Urology and Urological Oncology Department and Clinic
• Romania
  • Bucharest, Romania, 022328
    • Fundeni Clinical Institute
  • Cluj Napoca, Romania, 400015
    • "Prof. Dr. Ioan Chiricuta" Oncology Institute
  • Cluj-Napoca, Romania, 400058
    • Medisprof SRL
  • Cluj-Napoca, Romania, 400015
    • "Prof. Dr. Ioan Chiricuta" Oncology Institute
  • Craiova, Romania, 200385
    • Sc Oncolab Srl
  • Oradea, Romania, 410469
    • Emergency Clinical County Hospital Oradea
  • Targu-Mures, Romania, 540142
    • Targu-Mures Clinical County Hospital, Oncology and Radiotherapy Department
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
    • State Budget Institution of Healthcare "Chelyabinsk regional clinical oncological Dispensary"
  • Kazan, Russian Federation, 420029
    • Republican Clinical Oncology Dispensary of Ministry of Health of Republic Tatarstan
  • Moscow, Russian Federation, 115478
    • Institution of Russian Academy of Medical Science, "Russian Oncological Scientific Center named after N.N. Blokhin of Russian Academy of Medical Science"
  • Moscow, Russian Federation, 117997
    • Federal State Institution "Russian Scientific Center of Radiology and Nuclear Medicine of Healthcare of Russian Federation"
  • Moscow, Russian Federation, 125284
    • Moscow Hertsen Scientific Research Oncological Institute
  • Moscow, Russian Federation, 129327
    • State Institution "City Clinical Hospital NO20"
  • Orenburg, Russian Federation, 460021
    • Orenburg Regional Clinical Oncological Dispensary
  • Rostov-on-Don, Russian Federation, 344022
    • State Educational Institution of High Professional Education "Rostov State Medical University of Roszdrav"
  • Ryazan, Russian Federation, 390011
    • State Budget Institution of Ryazan Region "Regional Clinical Oncological Diespensary"
  • Saratov, Russian Federation, 410004
    • Nonstate Institution of Healthcare "Railway clinical Hospital at Station Saratov-2 of "RZGD" PC"
  • St. Petersburg, Russian Federation, 191104
    • State Institution of Healthcare "Leningrad Regional Oncological Dispensary"
  • St. Petersburg, Russian Federation, 194354
    • Saint-Petersburg State Institution of Healthcare "City Universal Hospital N02"
  • St. Petersburg, Russian Federation, 197022
    • Saint Petersburg State Institution of Healthcare "City Clinical Oncological Dispensary"
  • St. Petersburg, Russian Federation, 197758
    • Federal State Institution "Russian Scientific Center of Radiology and Surgery Technologies" of Ministry of Healthcare of Russian Federation"
  • St. Petersburg, Russian Federation, 197758
    • Federal State Institution "Scientific Research Institute of Oncology named after N.N. Petrov of Ministry of Healthcare of Russian Federation"
  • St. Petersburg, Russian Federation, 197758
    • Saint-Petersburg Clinical Scientific and Practical Centre of Special Methods of Medical Aid (Oncology)
  • Yaroslavl, Russian Federation, 150040
    • State Institution of Healthcare of Yaroslavl Region "Regional Clinical Oncological Hospital"
• United Kingdom
  • Bournemouth, United Kingdom, BH7 7DW
    • Royal Bournemouth Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrooke's Hospital & Peterborough District Hospital, Cambridge University Hospitals NHS Foundation Trust, Oncology Center
  • Leeds, United Kingdom, LS9 7TF
    • Leeds Institute of Molecular Medicine, Section of Oncology and Clinical Research, St. James's University Hospital
  • Manchester, United Kingdom, M20 4BX
    • Paterson Institute for Cancer Research, Christie Hospital NHS Foundation Trust, Medical Oncology
  • Oxford, United Kingdom, OX3 7LJ
    • Oxford Cancer and Haematology Centre, University of Oxford, The Churchill Hospital, Oxford Radcliffe Hospital NHS Trust, Dept.of Medical Oncology
  • Preston, United Kingdom, PR2 9HT
    • ROSEMERE CANCER CENTRE, Royal Preston Hospital, Lancashire Teaching Hospital
  • Southampton, United Kingdom, SO16 6YD
    • CRUK Research Unit, Somers Cancer Research Building, Southampton General Hospital
  • Surrey, United Kingdom, GU2 7WG
    • Postgraduate Medical School, University of Surrey
  • Swansea, United Kingdom, SA2 8QA
    • South West Wales Cancer Institute, Singleton Hospital, School of Medicine
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90048
      • Cedars-Siani Medical Center, Samuel Oschin Comprehensive Cancer Institute
  • Colorado
    • Denver, Colorado, United States, 80205
      • Kaiser Permanente Oncology Hematology Clinic
  • District of Columbia
    • Washington, D.C., District of Columbia, United States, 20007
      • Georgetown University Medical Center, Lombardi Comprehensive Cancer Center
  • Florida
    • Orlando, Florida, United States, 32806
      • M.D. Anderson Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago Medicine
    • Peoria, Illinois, United States, 61615-7822
      • North Central Cancer Treatment Group, Illinois Cancer Care
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Iu Simon Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Weinberg Cancer Institute at Franklin Hospital
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • New York
    • Lake Success, New York, United States, 11042
      • Clinical Research Alliance
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Institute
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Pavilion, University of Pittsburgh Cancer Institute, Division of Hematology / Oncology
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • San Antonio, Texas, United States, 78258
      • South Texas Oncology & Hematology, P.A., The Start Center For Cancer Care
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Sunitinib; Sunitib as Standard therapy per Label.	Drug: Sunitinib; As per label.; Other Names: Sutent
EXPERIMENTAL: IMA901 plus GM-CSF added to sunitinib after single dose of cy; 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	Drug: Sunitinib; As per label.; Other Names: Sutent; Biological: GM-CSF; Intradermal injection of GM-CSF as adjuvant.; Other Names: Leukine; Sargramostim; Granulocyte macrophage-colony stimulating factor; Drug: Cyclophosphamide; One single low-dose i.v. infusion prior to the first vaccination; Other Names: Endoxan (EU name); Cytoxan (US name); Drug: IMA901; Intradermal vaccinations with IMA901 vaccine.; Other Names: IMA901 Vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall survival	2015 (estimated)

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival in biomarker-defined subgroup	2015 (estimated)
Progression-free survival	2014 (estimated)
Best tumor response	2014 (estimated)
Safety and tolerability	continuously
Cellular immunomonitoring	2014 (estimated)

Collaborators and Investigators

• Sponsor: Immatics Biotechnologies GmbH
• Investigators: Principal Investigator: Brian Rini, MD, Cleveland Clinic Taussig Cancer Institute; Principal Investigator: Tim Eisen, MD, Addenbrooke's Hospital University of Cambridge, UK

Publications and helpful links

General Publications

• Rini BI, Stenzl A, Zdrojowy R, Kogan M, Shkolnik M, Oudard S, Weikert S, Bracarda S, Crabb SJ, Bedke J, Ludwig J, Maurer D, Mendrzyk R, Wagner C, Mahr A, Fritsche J, Weinschenk T, Walter S, Kirner A, Singh-Jasuja H, Reinhardt C, Eisen T. IMA901, a multipeptide cancer vaccine, plus sunitinib versus sunitinib alone, as first-line therapy for advanced or metastatic renal cell carcinoma (IMPRINT): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2016 Nov;17(11):1599-1611. doi: 10.1016/S1470-2045(16)30408-9. Epub 2016 Oct 3.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): July 1, 2015
• Study Completion (ACTUAL): July 1, 2015

Study Registration Dates

• First Submitted: December 22, 2010
• First Submitted That Met QC Criteria: December 22, 2010
• First Posted (ESTIMATE): December 23, 2010

Study Record Updates

• Last Update Posted (ACTUAL): October 12, 2017
• Last Update Submitted That Met QC Criteria: October 4, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Metastatic Renal Cell Carcinoma; First line; Eligible for sunitinib
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Cyclophosphamide; Sunitinib; Sargramostim; Molgramostim
• Other Study ID Numbers: IMA901-301; 2010-022459-45 (EUDRACT_NUMBER)