Tolerability and Efficacy of UV1 Vaccine in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Planned for First-line Treatment With Pembrolizumab

Studien-Informationen Einschlusskriterien Studien-Rationale Studien-Arme Geprüfte Regime

Rekrutierend

NCT-Nummer:
NCT05075122

Studienbeginn:
August 2021

Letztes Update:
09.03.2022

Wirkstoff:
UV1, Sargramostim for Injection, Pembrolizumab Injection

Indikation (Clinical Trials):
Carcinoma, Carcinoma, Squamous Cell, Squamous Cell Carcinoma of Head and Neck

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Martin-Luther-Universität Halle-Wittenberg

Collaborator:
Ultimovacs ASA, Apotheke der Universitätsmedizin der Johannes Gutenberg-Universität Mainz (Germany), Axel Hinke. CCRC Cancer Clinical Research Consulting (Düsseldorf, Germany,

Studienleiter

Mascha Binder, MD
Principal Investigator
University Medical Center Halle, Department of Hematology and Oncology

Kontakt

Mascha Binder, MD
Kontakt:
Phone: 0049 345 557
Phone (ext.): 2054
E-Mail: mascha.binder@uk-halle.de» Kontaktdaten anzeigen

Christine Dierks, MD
Kontakt:
Phone: 0049 345 557
Phone (ext.): 2590
E-Mail: christine.dierks@uk-halle.de» Kontaktdaten anzeigen

Studienlocations
(3 von 10)

Universitätsklinikum Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie
Aachen
(Nordrhein-Westfalen)
GermanyNoch nicht rekrutierend» Google-Maps

Charité Universitätsmedizin, Comprehensive Cancer Center, Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie
Berlin
(Berlin)
GermanyNoch nicht rekrutierend» Google-Maps

Universitätsklinikum Greifswald, Klinik für Hals-, Nasen-, Ohrenkrankheiten, Kopf- und Halschirurgie
Greifswald
(Mecklenburg-Vorpommern)
GermanyNoch nicht rekrutierend» Google-Maps

Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Innere Medizin IV
Halle (Saale)
(Sachsen-Anhalt)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Hamburg, Universitäres Cancer Center Hamburg UCCH, Hubertus Wald Tumorzentrum
Hamburg
(Hamburg)
GermanyNoch nicht rekrutierend» Google-Maps

Klinikum St. Georg gGmbH
Leipzig
(Sachsen)
GermanyNoch nicht rekrutierend» Google-Maps

Universitätsklinikum Leipzig, Klinik und Poliklinik für HNO Heilkunde
Leipzig
(Sachsen)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Mainz, III. Medizinische Klinik und Poliklinik
Mainz
(Rheinland-Pfalz)
GermanyRekrutierend» Google-Maps

Klinikum Stuttgart, Klinik für Hämatologie, Onkologie und Palliativmedizin
Stuttgart
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps

Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken
Würzburg
(Bayern)
GermanyNoch nicht rekrutierend» Google-Maps

Alle anzeigen

Studien-Informationen

Detailed Description:

Overall survival of patients with metastatic or recurrent HNSCC has improved over the past

decade but remains poor overall. Median overall survival is limited to less than 15 months,

with the current standard of care (immune checkpoint blockade with or without chemotherapy).

Many patients with HNSCC are frail and therefore cannot tolerate chemotherapy, reducing their

treatment options to checkpoint inhibitor. Therefore, the development of effective and

tolerable combination regimens is urgently needed, especially in first-line therapy. The

FOCUS study will evaluate such a combination regimen in patients with metastatic or recurrent

HNSCC. The experimental regimen evaluated in this study will test the first-line standard

drug pembrolizumab in combination with the novel UV1 cancer vaccine. In the comparator arm,

patients receive pembrolizumab as the standard of care. The aim is to assess whether the

addition of UVI can increase the efficacy of the checkpoint inhibitor. Based on currently

available data, a decrease in efficacy due to the combination of standard first-line therapy

with pembrolizumab is unlikely. The FOCUS study could therefore establish a new 1st-line

regimen with increased efficacy and acceptable tolerability, which would need to be compared

with the standard of care in a larger phase III trial. Based on the biomarker data from the

FOCUS study, a subsequent Phase 3 study would potentially test the regimen only in

subpopulations with increased response probability. From the perspective of the individual

patient, participants may benefit from the experimental combination through improved

efficacy. On the other hand, this is a novel combination study for HNSCC, and there is a risk

that efficacy may not improve.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Histologically confirmed diagnosis of a non-resectable recurrent or metastatic head

and neck squamous cell carcinoma (not necessarily reconfirmed at time of enrolment)

- At least one measurable tumor lesion as per RECIST v1.1, (Scan not older than 4 weeks

before randomization)

- Eligible for pembrolizumab monotherapy (PD-L1 CPS >/= 1% and adequate laboratory

parameters for pembrolizumab monotherapy as assessed by the investigator)

- ECOG-performance score 0-2

- Written informed consent obtained according to international guidelines and local laws

- Ability to understand and give informed consent.

- Safe contraception measures for males and females. Procedures with a pearl index of

less than 1% apply as safe pregnancy prevention measures.

Exclusion Criteria:

- Patients for whom a combination therapy of a checkpoint inhibitor and a chemotherapy

is deemed necessary in the opinion of the investigator

- Participation in another interventional study simultaneously and within the last 30

days prior to inclusion (registries or observational studies allowed)

- Concurrent malignancies other than disease under study within 5 years prior to

inclusion, with the exception of those with a negligible risk of metastasis or death

(e.g., expected 5-year OS > 90%) treated with expected curative outcome

- Active, known, or suspected autoimmune disease requiring systemic treatment.

- A concomitant therapy with systemic immune suppression: use of chronic systemic

steroid medication (up to 5 mg/day prednisolone equivalent is allowed; patients using

physiological replacement doses of prednisone for adrenal or pituitary insufficiency

are eligible)

- History of severe autoimmune disorder or history of organ transplant

- Any serious or uncontrolled medical disorder or active infection that, in the opinion

of the investigator, may increase the risk associated with study participation, study

drug administration, or would impair the ability of the subject to receive study drug.

- Significant acute or chronic infections including, among others (test not older than 4

weeks prior to randomization): Any positive test for human immunodeficiency virus

(HIV) or known acquired immunodeficiency syndrome (AIDS), Any positive test result for

hepatitis B virus or hepatitis C virus indicating acute or chronic infection.

- Pregnancy or lactation

- (Bacterial) infections requiring systemic antibiotic treatment within 2 weeks prior to

first dose of study treatment (depending on group assignment: either prior to first

UV1 or prior to first pembrolizumab administration).

- History of allergy or hypersensitivity to study drug or human granulocyte-macrophage

colony stimulating factor, yeast-derived products or any constituent of the products

- Receipt of a live vaccine within 30 days prior to start of therapy

- Patient who has been incarcerated or involuntarily institutionalized by court order or

by the authorities.

- Patients who are unable to consent because they do not understand the nature,

significance and implications of the clinical study and therefore cannot form a

rational intention in the light of the facts.

Studien-Rationale

Primary outcome:

1. Progression free survival rate (Time Frame - 6 months after first administration of study medication):
according to iRECIST

Secondary outcome:

1. Progression free survival (Time Frame - every three months, until progression of disease, maximum 12 months from the date of LPI (last patient in)):
according to iRECIST

2. Overall survival (Time Frame - every three months, until death, maximum 12 months from the date of LPI (last patient in))

3. Objective Response Rate (Time Frame - every three months, until death, maximum 12 months from the date of LPI (last patient in)):
Complete Remission (CR) + Partial Remission (PR) according to iRECIST

4. Duration of Response (Time Frame - every three months, until death, maximum 12 months from the date of LPI (last patient in)):
according to iRECIST

5. Rate of immune responses against hTERT peptides (Time Frame - Baseline, up to 8 weeks, time of progression (max. 12 months after LPI)):
measured by 3H-Thymidine proliferation and IFNgamma ELISPOT assays

6. Rate of clearance of ctDNA from blood on treatment (Time Frame - Baseline, week 5, week 8 and 1, 3, 6 months after EOT (max. 14 weeks), time of progression (max. 12 months after LPI))

7. Adverse Events (Time Frame - 3 months after EOT (maximum 25 weeks after start of treatment)):
according to NCI CTC AE v5.0

Studien-Arme

Experimental: Vaccination arm
Pembrolizumab flat dose iv every 3 weeks + UV1 vaccination (UV1 plus GM-CSF/Sargramostim as adjuvant per vaccination)
Other: Calibration arm
Pembrolizumab flat dose iv every 3 weeks

Geprüfte Regime

UV1:
UV1 vaccination (300 μg) UV1 vaccination will be applied in a dense schedule with three vaccinations during one week before initiation of pembrolizumab, followed by 5 additional vaccinations every 3 weeks on d1 of each cycle (5 cycles in total, duration of treatment will be 13 weeks in total, regular EOT at week 14)
Sargramostim for Injection:
75 μg GM-CSF as adjuvant per vaccination. Applied in a dense schedule with three injections during one week before initiation of pembrolizumab, followed by 5 additional injections every 3 weeks on d1 of each cycle (5 cycles in total, duration of treatment will be 13 weeks in total, regular EOT at week 14).
Pembrolizumab injection:
200mg flat dose iv every 3 weeks. Pembrolizumab will be administered beyond the EOT visit at physician discretion until disease progression and up to a maximum of two years (standard of care)

Quelle: ClinicalTrials.gov

Sie können folgenden Inhalt einem Kollegen empfehlen:

"Tolerability and Efficacy of UV1 Vaccine in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma Planned for First-line Treatment With Pembrolizumab"

Bitte tragen Sie auch die Absenderdaten vollständig ein, damit Sie der Empfänger erkennen kann.

Die mit (*) gekennzeichneten Angaben müssen eingetragen werden!