JOURNAL ONKOLOGIE – STUDIE

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

Studien-Informationen Einschlusskriterien Studien-Rationale Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05641545

Studienbeginn:
Oktober 2022

Letztes Update:
07.12.2022

Wirkstoff:
IVAC

Indikation (Clinical Trials):
Carcinoma, Renal Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
SLK Kliniken Heilbronn GmbH

Collaborator:
-

Kontakt

Uwe Martens, MD
Kontakt:
Phone: 004971314928000
E-Mail: uwe.martens@slk-kliniken.de» Kontaktdaten anzeigen

Studienlocations
(1 von 1)

SLK Kliniken Heilbronn, Klinik für Innere Medizin III: Hämatologie, Onkologie, Palliativmedizin
74078 Heilbronn
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Uwe Martens, MD
Phone: 004971314928000
E-Mail: uwe.martens@slk-kliniken.de

Josef Huber, MD
E-Mail: josef.huber@slk-kliniken.de» Ansprechpartner anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

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 unacceptable toxicities (grade 4 according to NCI-CTC) and in whom 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:

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.

Geprüfte Regime

IVAC:
IVAC is a personalized peptide vaccine

Quelle: ClinicalTrials.gov

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