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IVAC-RCC-001: A Personalized Neoantigen Vaccine as Add-on to Standard of Care Checkpoint Inhibitor in Advanced/Metastatic RCC Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05641545
Recruitment Status : Recruiting
First Posted : December 7, 2022
Last Update Posted : December 7, 2022
Sponsor:
Information provided by (Responsible Party):
Uwe Martens, SLK Kliniken Heilbronn GmbH

Brief Summary:
This is a monocenter, single-arm, prospective phase Ib trial, designed to evaluate the safety, clinical toxicity and in vivo immunological effects of a patient-individualized peptide vaccination added to standard of care checkpoint blockade (nivolumab) in adult patients with metastatic/advanced renal cell carcinoma who experienced at least stable disease after four cycles of standard of care immune therapy (ipilimumab/nivolumab).

Condition or disease Intervention/treatment Phase
Advanced Renal Cell Carcinoma Biological: IVAC Phase 1

Detailed Description:
The aim of this clinical study is to evaluate the feasibility and safety of an individualized peptide vaccination approach in patients with advanced renal cell carcinoma who experienced at least stable disease after four cycles of standard of care immune therapy (ipilimumab/nivolumab). For this purpose, tumor-specific mutations are analyzed by comparative exome sequencing of tumor and healthy reference tissue. In a second step, HLA-binding (human leukocyte antigen-binding) peptides derived from mutated protein sequences are selected for vaccination. The peptides are administered as a vaccination cocktail with adjuvant GM-CSF and Imiquimod over a course of 9 months and a total of 16 vaccinations. Primary objective is the de novo induction of a specific T cell response without unacceptable toxicity.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: IVAC-RCC-001: A Personalized Neoantigen Vaccine as Add-on to Standard of Care Checkpoint Inhibitor in Advanced/Metastatic RCC Patients
Actual Study Start Date : October 17, 2022
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : November 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arm Intervention/treatment
Experimental: IVAC-RCC-001
Individual peptide vaccination with adjuvant GM-CSF and Imiquimod Intradermal injection of a cocktail of 3-5 individual HLA-binding peptides. Subcutaneous injection of adjuvant GM-CSF at vaccination site. Topical administration of Imiquimod at vaccination site.
Biological: IVAC
IVAC is a personalized peptide vaccine




Primary Outcome Measures :
  1. Primary endpoint is "success of treatment" defined as a patient without unacceptable toxicity and showing a vaccination-induced T-cell response. [ Time Frame: 120 days ]

    Treatment success is defined as a patient without

    1. unacceptable toxicities (grade 4 according to NCI-CTC) and in whom
    2. a vaccine-specific response of CD4+ and/or CD8+ T cells could be induced. The primary endpoint will be analyzed after 10 patients have reached visit 10


Secondary Outcome Measures :
  1. To evaluate CD4+ and/or CD8+ T-cell responses over the vaccination period. [ Time Frame: 246 days ]
    T-cell responses will be measured after completion of the study and will be analyzed with regard to the T-cell responses after 10 vaccinatuions /at day 120.

  2. To evaluate the event-free survival (EFS) during and after treatment. [ Time Frame: 246 days ]
    EFS will be assessed on days 120 and 246.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 or older
  • Ability to understand and willingness to sign a written informed consent document.
  • Patients with RCC Stage IV (AJCC 8th ed.) of any histology, not amenable to curative surgery, minimal-invasive therapy or radiation therapy
  • Intermediate/poor risk by IMDC (≥1 risk factors)
  • ECOG 0-1
  • Patients with advanced or metastatic disease occurring subsequent to initial curative nephrectomy or subsequent to other previous therapy with curative intent are eligible
  • Measurable disease as per RECIST 1.1 (at least one measurable lesion)
  • Participants must be eligible to be treated with first line Nivolumab+Ipilimumab based on investigator´s judgement.
  • Patients must have adequate fresh tissue available. If a fresh tissue sample is not available by routine procedures, participants must have a lesion amenable to fresh tumor biopsy at study entry for the next generation sequencing (NGS) required for this study and willing to provide informed consent for such biopsy. FFPE tumor samples are not suitable for the NGS required for this study.
  • Patient is agreeable to allow tumor and blood samples to be submitted for complete exome and transcriptome sequencing.
  • No previous systemic therapy for advanced or metastatic RCC
  • Patients with 3 or fewer brain metastases that are < 1 cm in diameter and asymptomatic are eligible if clinically stabe
  • Participants must have normal organ and bone marrow function as defined below Leukocytes ≥3,000/mcL Absolute neutrophil count ≥1,000/mcL Platelets ≥100,000/mcL Total bilirubin within 1,5 ULN AST(SGOT)/ALT(SGPT) ≤5 × institutional upper limit of normal Creatinine Clearance ≥40 mL/min/(calculated using the Cockroft-Gault equation)
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test before entry onto the trial and within 2 days prior to start of study medication.
  • Female patients enrolled in the study, who are not free from menses for >2 years, post hysterectomy / oophorectomy, or surgically sterilized, must be willing to use either 2 adequate barrier methods or a barrier method plus a hormonal method of contraception to prevent pregnancy or to abstain from sexual activity for the duration of vaccine treatment plus 30 days (duration of ovulatory cycle).

Exclusion Criteria:

  • Prior treatment with any anti-programmed cell death (anti-PD-1), or anti-programmed cell death ligand 1 (anti-PD-L1) agent or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
  • Prior systemic anti-cancer therapy for RCC with vascular endothelial growth factor (VEGF)/VEGF receptors (VEGFR) or mechanistic target of rapamycin (mTOR) targeting agents. Prior systemic anti-cancer therapy for curative intent with VEGFR or mTOR targeting agents is allowed if discontinued >6 months prior to enrolment.
  • Prior RCC-directed cancer vaccine therapy.
  • Any history of a known or suspected autoimmune disease [e.g. including but not limited to inflammatory bowel diseases, rheumatoid arthritis, autoimmune thyroiditis, autoimmune hepatitis, systemic sclerosis (scleroderma and variants), systemic lupus erythematosus, autoimmune vasculitis, autoimmune neuropathies (such as Guillain-Barre syndrome) or recent history of a syndrome that required systemic corticosteroids (> 10 mg daily prednisone equivalent) or immunosuppressive medications except for syndromes which would not be expected to recur in the absence of an external trigger. Participants with vitiligo or type I diabetes mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement are permitted to enroll.
  • Any condition requiring systemic treatment with corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to first dose of study drug. Inhaled steroids and adrenal replacement steroid doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
  • Active brain metastases or leptomeningeal metastases
  • Positive serological test for hepatitis C virus ot hepatitis B virus surface antigen (HBsAg) or or human immunodeficiency virus (HIV)
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring IV antibiotic treatment, symptomatic congestive heart failure, unstable angina pectoris, clinically relevant cardiac arrhythmia.
  • Any known medical condition that, in the investigator's opinion, would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05641545


Contacts
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Contact: Uwe Martens, MD 004971314928000 uwe.martens@slk-kliniken.de

Locations
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Germany
SLK Kliniken Heilbronn, Klinik für Innere Medizin III: Hämatologie, Onkologie, Palliativmedizin Recruiting
Heilbronn, Germany, 74078
Contact: Uwe Martens, MD    004971314928000    uwe.martens@slk-kliniken.de   
Contact: Josef Huber, MD       josef.huber@slk-kliniken.de   
Sponsors and Collaborators
SLK Kliniken Heilbronn GmbH
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Responsible Party: Uwe Martens, Director of the Department of Hematology, Oncology and Palliative Care, SLK Kliniken Heilbronn GmbH
ClinicalTrials.gov Identifier: NCT05641545    
Other Study ID Numbers: IVAC-RCC-001
First Posted: December 7, 2022    Key Record Dates
Last Update Posted: December 7, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases