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Recurrent Vulvar CancerPhase 2PIERCENCT05903833

Pembrolizumab Combination With Lenvatinib in Pts With Recurrent,Persistent,Metastatic or Locally Advanced Vulvar Cancer Not Amenable to Curative Surgery or Radiotherapy

A Phase 2 study testing Pembrolizumab and Lenvatinib in people with Recurrent Vulvar Cancer and Persistent Vulvar Cancer, run by AGO Research GmbH at 15 sites in Germany.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Evaluation of efficacy and safety of pembrolizumab in combination with lenvatinib in patients with recurrent, persistent, metastatic or locally advanced vulva cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Pembrolizumab and Lenvatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
15 sitesGermany
Study dates
24 Jun 2025to 30 Oct 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Signed written informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patients awareness and willingness to comply with the study requirements.
  • Female patients who are at least 18 years of age on the day signing informed consent
  • Histologically confirmed locally advanced, recurrent, persistent and/or metastatic VSCC not amenable for salvage surgery or definitive (chemo)radiation (additive palliative radiotherapy for symptom control is allowed)
  • ≤2 previous lines of chemotherapy for recurrent or metastatic disease
  • Measurable disease (investigator assessed RECIST 1.1). Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Have an eastern cooperative oncology group (ECOG) performance status of 0-1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
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  • No pregnancy (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] or human chorionic gonadotropin [hCG]) test with a minimum sensitivity of 25 IU/L or equivalent units of ß-hCG [or hCG]), no breastfeeding, and at least one of the following conditions applies:
  • Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
  • A WOCBP who agrees to follow the contraception and pregnancy testing recommendations for investigational medicinal products (IMPs) with demonstrated or suspected human teratogenicity/ fetotoxicity in early pregnancy of the CTFG-guideline in Appendix 3 during the treatment period and for at least 4 months (corresponding to time needed to eliminate pembrolizumab) after the last dose of study treatment. In addition to the described highly effective oral/transdermal contraception methods a barrier method must be used.
  • A WOCBP should not become pregnant during the treatment and for at least 4 months.
  • Available archival tumor tissue sample and/or newly obtained core or excisional biopsy of a tumor lesion ideally not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
  • Adequate organ function as defined in Table 3 of study protocol. Specimens must be collected within 10 days prior to the start of study treatment.

Who cannot join

  • Non squamous cell histology
  • Contraindications regarding treatment with pembrolizumab:
  • allergy or hypersensitivity to pembrolizumab or one of the components.
  • Contraindications regarding treatment with lenvatinib: allergy or hypersensitivity to lenvatinib or one of the components or:
  • Pre-existing ≥Grade 3 gastrointestinal or nongastrointestinal fistula
  • Radiographic evidence of major blood vessel infiltration
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  • Bradyarrhythmia
  • Arterial dissection/aneurysm
  • Long QT Syndrome
  • Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 12 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at screening.
  • History or evidence of major thrombotic (e.g. symptomatic pulmonary embolism) or hemorrhagic disorders within 6 months prior to day 1, cycle 1. The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe haemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
  • Allogenic tissue/solid organ transplant.
  • Diagnosis of immunodeficiency
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years (time requirement does not apply for definitively treated early endometrial cancer (FIGO IA/B), in-situ carcinomas [e.g. breast, cervix, bladder], or basal or squamous cell carcinoma of the skin).
  • Gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
  • Active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
  • History of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Major active infection requiring systematic therapy.
  • Has active hemoptysis within 3 weeks prior to the first dose of study intervention or tumor bleeding within 2 weeks prior randomization.
  • Known history of Human Immunodeficiency Virus (HIV) infection
  • History of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
  • Known history of active TB (Bacillus tuberculosis).
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Pregnancy
  • Breastfeeding Prior/ Concomitant Therapy
  • Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
  • Systemic use of corticosteroids or immunosuppressive drugs within 7 days prior start of study treatment (see EC 11.)
  • Systemic corticosteroids (at dose higher than 10 mg/day equivalent prednisone); if systemic corticoid use, corticoid must be stopped at least 7 days before study treatment start
  • Interferons
  • Interleukins
  • Live vaccine
  • Note: Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed as other killed vaccines, if done at least 2 weeks prior the first dose of study drug; however, intranasal influenza vaccines (e.g. FluMist®) are live attenuated vaccines and are not allowed.
  • Antiarrhythmics of classes Ia and III and other QT-interval prolongation drugs
  • Prior systemic anti-cancer therapy including investigational agents within 4 weeks [could consider shorter interval for kinase inhibitors or other short half-life drugs] prior to allocation.
  • Prior radiotherapy within 2 weeks of start of study intervention. Patients must have recovered from radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • Not recovered adequately from any toxicity from other anticancer treatment regimens and/or complications from major surgery prior to starting therapy. Note: Withhold lenvatinib for at least 1 week prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing.
  • Administration of a live, attenuated vaccine within 30 days prior first dose of study drug. Diagnostic Assessments
  • Uncontrolled blood pressure (Systolic BP >140 mmHg or diastolic BP >90 mmHg) in spite of an optimized regimen of antihypertensive medication.
  • Change of anti-HTN (hypertension) medical regimen within 1 week prior to randomization
  • Prolongation of corrected QT interval (QTc interval) >480 ms
  • Left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
  • Electrolyte abnormalities that have not been corrected.
  • Subjects having >1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is <1 g/24 hours. Prior/Concurrent Study Experience
  • Prior enrolment on a clinical study evaluating pembrolizumab and lenvatinib for a carcinoma, regardless of treatment received.
  • Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention. Note: Patients who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.

Trial locations and contacts

15 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Yvonne Treffner, Dr. contact

+49 201 959812-17

ytreffner@ago-ovar.de

Office -Essen contact

+49 201 959812-20

office-essen@ago-ovar.de

15 sites in 1 country

Germany15 sites, 15 recruiting

  • Universitätsklinikum Augsburg

    Augsburg

    Recruiting

  • Hochtaunus-Kliniken Bad Homburg

    Bad Homburg

    Recruiting

  • Universitätsklinikum Carl Gustav Carus Dresden

    Dresden

    Recruiting

  • Universitätsklinikum Düsseldorf

    Düsseldorf

    Recruiting

  • KEM Kliniken Essen-Mitte

    Essen

    Recruiting

  • Universitätsklinikum Essen

    Essen

    Recruiting

  • Universitätsmedizin Göttingen

    Göttingen

    Recruiting

  • University Hospital Hamburg

    Hamburg

    Recruiting

  • Klinikum Hanau GmbH

    Hanau

    Recruiting

  • ZAGO - Zentrum für ambulante gynäkologische Onkologie

    Krefeld

    Not yet recruiting

  • Universitätsmedizin Mainz

    Mainz

    Recruiting

  • Universitätsklinikum Mannheim

    Manheim

    Recruiting

  • Klinikum der Universität München, LMU

    München

    Recruiting

  • Universitätsklinikum Münster

    Münster

    Recruiting

  • University Hospital

    Tübingen

    Recruiting

Other trials in Germany

About this study

Official title: Pembrolizumab in Combination With Lenvatinib in Pts With Recurrent, Persistent, Metastatic or Locally Advanced Vulvar Cancer Not Amenable to Curative Surgery or Radiotherapy

Evaluation of efficacy and safety of pembrolizumab in combination with lenvatinib in patients with recurrent, persistent, metastatic or locally advanced vulva cancer.

Read the detailed description

A multicenter, single-arm phase II, open-label study, to evaluate the efficacy and safety of pembrolizumab 400 mg Q6W in combination with lenvatinib 20 mg QD in patients with recurrent, persistent, metastatic or locally advanced VSCC not amenable to salvage surgery or definitive (chemo)radiation.

Keywords
Advanced vulvar cancer, Recurrent vulvar cancer, Persistent vulvar canser, Metastatic vulvar cancer, Locally advanced vulvar cancer, Pembrolizumab, Lenvatinib
Medical subject headings
Vulvar Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT05903833
Study groupRoleWhat they receive
Treatment allocationExperimentalAdministration of pembrolizumab 400 mg Q6W in combination with lenvatinib 20 mg QD
Receives: Drug: Pembrolizumab; Drug: Lenvatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ORR within 24 weeks

    ORR will be defined as the proportion of patients with PR or CR within 24 weeks starting with the first study treatment. Tumor responses will be assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

    Measured: 24 weeks

Secondary outcomes (10)

  1. Evaluate the efficacy of lenvatinib + pembrolizumab in terms of overall ORR

    Overall ORR

    Measured: From date of starting study treatment until the date of first documented progression or date of death from any cause, whichever occurs earlier, assessed up to 40 months

  2. Evaluate the efficacy of lenvatinib + pembrolizumab in terms of disease control rate (DCR)

    DCR will be defined as the proportion of patients with PR, CR or stable disease (SD)

    Measured: For 8 weeks

  3. Evaluate the efficacy of lenvatinib + pembrolizumab in terms of duration of response (DOR)

    DOR will be defined as time from response until first progression or death, whichever occurs first

    Measured: Time from response until first progression or death, whichever occurs first, assessed up to 40 months

  4. Evaluate the efficacy of lenvatinib + pembrolizumab in terms of overall survival (OS)

    OS will be defined as the time from date of starting study treatment to death.

    Measured: Time from date of starting study treatment to death, assessed up to 40 months

  5. Evaluate the efficacy of lenvatinib + pembrolizumab in terms of progression free survival (PFS)

    PFS will be defined as the time from starting study treatment to progressive disease (PD) or death, whichever occurs first

    Measured: Time from starting study treatment to progressive disease or death, whichever occurs first, assessed up to 40 months

  6. Evaluate the efficacy of lenvatinib + pembrolizumab in terms of time to first subsequent therapy (TFST)

    • TFST will be defined as the time from date of starting study treatment until the start of the first subsequent therapy or death whichever occurs first.

    Measured: The time from date of starting study treatment until the start of the first subsequent therapy or death whichever occurs first, assessed up to 40 months

  7. Evaluate the efficacy of lenvatinib + pembrolizumab in terms of time to second subsequent therapy (TSST)

    • TSST will be defined as the time from date of starting study treatment until the start of second subsequent treatment or death whichever occurs first.

    Measured: Time from date of starting study treatment until the start of second subsequent treatment or death whichever occurs first, assessed up to 40 motnhs

  8. Patient reported outcomes (QLQ)

    Quality of life is measured by patient reported outcome instruments EORTC QLQ C-30 to evaluate the efficacy of combination of lenvatinib and pembrolizumab

    Measured: Assessed frequently during the trial up to 40 months

  9. Patient reported outcomes (QLQ)

    Quality of life is measured by patient reported outcome instruments EORTC QLQ VU34 to evaluate the efficacy of combination of lenvatinib and pembrolizumab

    Measured: Assessed frequently during the trial up to 40 months

  10. Number of participants with treatment-related adverse events (AE) and/or serious adverse events (SAEs) and/or AEs that led to premature withdrawal of trial treatment and/or interruptions/dose modifications

    Graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, to evaluate the safety and tolerability of the combination of lenvatinib and pembrolizumab

    Measured: At every visit during the trial up to safety follow, thereafter up to 120 days after administration of last dose of study medication

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2023
  2. Study start24 Jun 2025
  3. Primary completion30 Oct 2027 (estimated)
  4. Study completion30 Oct 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
42 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05903833
Sponsor's protocol ID
AGO-Vulva 1
Other IDs
2024-515646-16-00
Acronym
PIERCE
Status last verified
May 2026
First submitted
11 May 2023
Last updated
11 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Lenvatinib in people with Recurrent Vulvar Cancer and Persistent Vulvar Cancer, run by AGO Research GmbH at 15 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Yvonne Treffner, Dr. (+49 201 959812-17, ytreffner@ago-ovar.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ORR within 24 weeks (time frame: 24 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05903833.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 May 2026.

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