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 (FOCUS)

March 8, 2022 updated by: Mascha Binder, MD, Martin-Luther-Universität Halle-Wittenberg

Phase 2 Multicenter Study Investigating the Tolerability and Efficacy of UV1 Vaccine in Patients With Recurrent or Metastatic PD-L1 Positive (CPS≥1) Head and Neck Squamous Cell Carcinoma Planned for First-line Treatment With Pembrolizumab

The primary objective of this study is to determine the clinical performance of UV1 vaccination as add on to standard pembrolizumab treatment in patients with recurrent or metastatic PD-L1 positive (CPS >=1) head and neck squamous cell carcinoma. Secondary objectives are to determine the efficacy in terms of overall survival ,objective response rate and duration of response. Moreover, this study will explore patient subgroups most likely deriving benefit from a targeted immunotherapy approach combining a checkpoint inhibitor with a cancer vaccine and help to establish liquid biopsy tumor monitoring in HNSCC.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
75

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Germany
      • Aachen, Germany
        • Not yet recruiting
        • Universitätsklinikum Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie
      • Berlin, Germany
        • Not yet recruiting
        • Charité Universitätsmedizin, Comprehensive Cancer Center, Medizinische Klinik m.S. Hämatologie, Onkologie und Tumorimmunologie
      • Greifswald, Germany
        • Not yet recruiting
        • Universitätsklinikum Greifswald, Klinik für Hals-, Nasen-, Ohrenkrankheiten, Kopf- und Halschirurgie
      • Halle (Saale), Germany
        • Recruiting
        • Universitätsklinikum Halle (Saale), Klinik und Poliklinik für Innere Medizin IV
      • Hamburg, Germany
        • Not yet recruiting
        • Universitätsklinikum Hamburg, Universitäres Cancer Center Hamburg UCCH, Hubertus Wald Tumorzentrum
      • Leipzig, Germany
        • Not yet recruiting
        • Klinikum St. Georg gGmbH
      • Leipzig, Germany
        • Recruiting
        • Universitätsklinikum Leipzig, Klinik und Poliklinik für HNO Heilkunde
      • Mainz, Germany
        • Recruiting
        • Universitätsklinikum Mainz, III. Medizinische Klinik und Poliklinik
      • Stuttgart, Germany
        • Recruiting
        • Klinikum Stuttgart, Klinik für Hämatologie, Onkologie und Palliativmedizin
      • Würzburg, Germany
        • Not yet recruiting
        • Universitätsklinikum Würzburg, Comprehensive Cancer Center Mainfranken

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Vaccination arm
Pembrolizumab flat dose iv every 3 weeks + UV1 vaccination (UV1 plus GM-CSF/Sargramostim as adjuvant per vaccination)
Biological: 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)
Drug: 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).
Drug: 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)
Other: Calibration arm
Pembrolizumab flat dose iv every 3 weeks
Drug: 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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progression free survival rate
Time Frame: 6 months after first administration of study medication
according to iRECIST
6 months after first administration of study medication

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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
every three months, until progression of disease, maximum 12 months from the date of LPI (last patient in)
Overall survival
Time Frame: every three months, until death, maximum 12 months from the date of LPI (last patient in)
every three months, until death, maximum 12 months from the date of LPI (last patient in)
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
every three months, until death, maximum 12 months from the date of LPI (last patient in)
Duration of Response
Time Frame: every three months, until death, maximum 12 months from the date of LPI (last patient in)
according to iRECIST
every three months, until death, maximum 12 months from the date of LPI (last patient in)
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
Baseline, up to 8 weeks, time of progression (max. 12 months after LPI)
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)
Baseline, week 5, week 8 and 1, 3, 6 months after EOT (max. 14 weeks), time of progression (max. 12 months after LPI)
Adverse Events
Time Frame: 3 months after EOT (maximum 25 weeks after start of treatment)
according to NCI CTC AE v5.0
3 months after EOT (maximum 25 weeks after start of treatment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Martin-Luther-Universität Halle-Wittenberg

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Ultimovacs ASA
Apotheke der Universitätsmedizin der Johannes Gutenberg-Universität Mainz (Germany)
Axel Hinke. CCRC Cancer Clinical Research Consulting (Düsseldorf, Germany

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Mascha Binder, MD, University Medical Center Halle, Department of Hematology and Oncology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 2, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2024

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 21, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 29, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 12, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 9, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 8, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KKSH176
  • 2020-005910-17 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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