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Head and Neck Squamous Cell CarcinomaPhase 2NCT05433116

Pembrolizumab and Lenvatinib After Definitive Chemoradiation of Locally Advanced HNSCC

A Phase 2 study testing Pembrolizumab and Lenvatinib in people with Head and Neck Squamous Cell Carcinoma, run by Universität des Saarlandes at 10 sites in Germany.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Open-label, two-arm, prospective multicenter phase II clinical trial to determine the efficacy and safety of combined pembrolizumab and lenvatinib compared to pembrolizumab alone as maintenance therapy after definitive radiochemotherapy of locally advanced head and neck squamous cell carcinoma (HNSCC). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Head and Neck Squamous Cell Carcinoma
What is being tested?
Pembrolizumab and Lenvatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
10 sitesGermany
Study dates
25 May 2023to Jan 2027
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
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants are eligible to be included in the study only if all of the following criteria apply:
  • Male/female participants who are at least 18 years of age on the day of signing informed consent
  • Pathologically proven new diagnosis of squamous cell carcinoma (HNSCC) of the oral cavity, oropharynx, hypopharynx or supraglottic larynx stage III-IVB according to TMM 8th edition
  • PD-L1 combined positive score (CPS) ≥1 (in sample prior to radiochemotherapy) by central pathology review
  • Completed definitive radiochemotherapy up to at least 68Gy with at least 200mg/m² body surface area concomitant Cisplatin.
  • No progression during radiochemotherapy. Study screening CT has to be compared to radiochemotherapy baseline CT. (Study screening CT may be performed before the end of radiochemotherapy, whereas a minimum radiation dose of 50Gy has to be administered at the time point of the study screening CT.)
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  • Male participants:
  • A male participant must agree to use a contraception as detailed in Appendix 3 of this protocol during the treatment period and for at least 120 days after the last dose of study treatment (pembrolizumab or lenvatinib, whichever is administered last) and refrain from donating sperm during this period. In addition, contraception has to be used for 180 days after the last dose of cisplatin.
  • Female participants:
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP) OR b. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment (pembrolizumab or lenvatinib, whichever is administered last). In addition, contraception has to be used for 180 days after the last dose of cisplatin.
  • The participant provides written informed consent for the trial.
  • Have measurable disease based on RECIST 1.1.
  • Have provided archival tumor tissue sample with sufficient tumor content. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
  • Have adequate organ function. Specimens must be collected within 10 days prior to the start of study intervention.

Who cannot join

  • Participants are excluded from the study if any of the following criteria apply:
  • Have tumor infiltration/perforation of the skin or cervical fistula (either at timepoint of study inclusion or prior to radiochemotherapy)
  • Have radiographic evidence of major blood vessel invasion/infiltration or tumor demonstrates >90-degree abutment or encasement of a major blood vessel.
  • Had prior radical surgery for the head and neck cancer under study or induction chemotherapy with more than one cycle prior to definitive radiochemotherapy. Patients with single cycle induction chemotherapy prior radiochemotherapy can be included.
  • WOCBP who have a positive urine or serum pregnancy test within 72 hours prior to. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Have received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
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  • Have received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to study drug administration (except from cisplatin concomitant to radiochemotherapy).
  • Have received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
  • Are currently participating in or have participated in a study of an investigational agent or have used an investigational device within 4 weeks prior to the first dose of study intervention.
  • Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
  • Have a known additional malignancy that is progressing or have required active treatment within the past 3 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
  • Have distant metastases.
  • Have severe hypersensitivity (≥Grade 3) to pembrolizumab, lenvatinib and/or any of their excipients.
  • Have 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • Have a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
  • Have an active infection requiring systemic therapy.
  • Have a known history of Human Immunodeficiency Virus (HIV) infection.
  • Have a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA is detected) infection.
  • Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
  • Have known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment. (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]).
  • Have had an allogenic tissue/solid organ transplant.
  • Have uncontrolled blood pressure (Systolic BP>140 mmHg or diastolic BP >90 mmHg) in spite of an optimized regimen of antihypertensive medication.
  • Have clinically relevant electrolyte abnormalities that have not been corrected.
  • Have significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening.
  • Have/had bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
  • Have > 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.
  • Have not recovered adequately from any toxicity from other anti- cancer treatment regimens and/or complications from major surgery prior to starting therapy. 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.
  • Have prolongation of QTc interval to >480 ms in the ECG.
  • Have a LVEF below the institutional (or local laboratory) normal range, as determined by multigated acquisition (MUGA) or echocardiogram (ECHO).
  • Active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

Germany10 sites

  • University Hospital Augsburg, Radiation Oncology

    Augsburg, Bavaria, 86156

  • Hospital Chemnitz, Radiation Oncology

    Chemnitz, Saxony, 09116

  • Gemeinschaftspraxis Hämatologie-Onkologie

    Dresden, Saxony, 01307

  • University Hospital Düsseldorf, Radiation Oncology

    Düsseldorf, North Rhine-Westphalia, 40225

  • University Hospital Erlangen, Radiation Oncology

    Erlangen, Bavaria, 91054

  • University Hospital Frankfurt/M, Center for Radiology

    Frankfurt am Main, Hesse, 60590

  • University Hospital Giessen; Ear, nose and throat clinic

    Giessen, Hesse, 35392

  • Saarland University Medical Center and Saarland University Faculty of Medicine, Clinic for Radiotherapy and Radiooncology

    Homburg, Saarland, 66421

  • University Hospital Regensburg, Clinic and Polyclinic for Radiotherapy

    Regensburg, Bavaria, 93053

  • University Hospital Ulm, Otolaryngology & Head and Neck Surgery

    Ulm, Baden-Wurttemberg, 89070

Other trials in Germany

About this study

Official title: Combined Pembrolizumab and Lenvatinib After Definitive Chemoradiation of Locally Advanced HNSCC in PD-L1 Positive Patients (CPS≥1)

Open-label, two-arm, prospective multicenter phase II clinical trial to determine the efficacy and safety of combined pembrolizumab and lenvatinib compared to pembrolizumab alone as maintenance therapy after definitive radiochemotherapy of locally advanced head and neck squamous cell carcinoma (HNSCC).

Read the detailed description

This is an open-label, two-arm, prospective multicenter phase II clinical trial to determine the efficacy and safety combined pembrolizumab and lenvatinib compared to pembrolizumab alone as maintenance therapy after definitive radiochemotherapy of locally advanced head and neck squamous cell carcinoma (HNSCC). The trial will be conducted in conformance with Good Clinical Practices and subjects will be enrolled into the trial by signing the informed consent form (ICF). Only subjects with PD-L1 positive (CPS≥1) tumors according to centralized reference pathologic assessment can be enrolled. Subjects without disease progression in the study screening CT (compared to radiochemotherapy baseline CT) that fulfil all further eligibility criteria can enter the trial after completion of definitive radiochemotherapy. Sites will be required to submit tissue samples for PD-L1 assessment in central pathology.

After confirmed study inclusion, patients will be randomized to receive either combined pembrolizumab and lenvatinib (treatment arm A) or pembrolizumab alone (treatment arm B). Pembrolizumab will be administered intravenously at a dose of 200mg q3w and lenvatinib at a dose of 20mg once daily orally. The first dose of pembrolizumab has to be administered within 14 days after completion of radiochemotherapy. Treatment with lenvatinib will start concomitant to cycle 2 of pembrolizumab. Treatment will be continued until disease progression, unacceptable adverse event(s) or until the subject has received 12 months of treatment (i.e. 17 doses of pembrolizumab). Afterwards patients will enter follow-up until 24 months since study inclusion.

It is planned to randomize 48 patients. In addition, two patients are treated in advance as proof on concept with pembrolizumab and lenvatinib. Primary endpoint of the trial is the event-free survival (EFS) rate at 2 years. The aim of the trial is to increase the 2-year EFS rate from 60% to 80%. This improvement is considered to be a clinically relevant advantage.

Medical subject headings
Squamous Cell Carcinoma of Head and Neck

What participants receive

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

  • PembrolizumabDrug

    Also called Keytruda

    i.v., 200mg absolute, q3w, starting within 14 days after completion of radiochemotherapy

  • LenvatinibDrug

    Also called Lenvima

    20mg once daily orally, start concomitant to cycle 2 of pembrolizumab

Study groups in NCT05433116
Study groupRoleWhat they receive
pembrolizumab + lenvatinibOthercombined pembrolizumab (200mg q3w) and lenvatinib treatment (20mg once daily)
Receives: Drug: Pembrolizumab; Drug: Lenvatinib
pembrolizumabOtherpembrolizumab (200mg q3w)
Receives: Drug: Pembrolizumab

What is being measured

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

  1. Event-free survival (EFS) rate

    To study efficacy of pembrolizumab/lenvatinib maintenance therapy versus pembrolizumab alone after definitive RCT of locally advanced HNSCC to prolong the event-free survival (EFS) rate at 2 years.

    Measured: 2 years

Secondary outcomes (3)

  1. Event-free survival (EFS) (continuous)

    Pembrolizumab/lenvatinib maintenance therapy will improve further efficacy endpoints compared to expectations derived from historical data on pembrolizumab alone.

    Measured: 2 years

  2. Locoregional control

    Locoregional progression will be evaluated by RECIST 1.1 criteria

    Measured: Restaging 12-13 weeks after completion of radiotherapy; Follow-up every 24 weeks

  3. Toxicity of Pembrolizumab/lenvatinib

    Toxicity will be evaluated according to CTCAE v5.0 criteria

    Measured: until safety follow-up (1 year treatment + 30 days)

Timeline

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

  1. First posted27 Jun 2022
  2. Study start25 May 2023
  3. Primary completionJan 2026 (estimated)
  4. Study completionJan 2027 (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
Randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05433116
Sponsor's protocol ID
PeLeRad
Other IDs
2021-004388-28
Status last verified
Oct 2025
First submitted
15 Jun 2022
Last updated
2 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab and Lenvatinib in people with Head and Neck Squamous Cell Carcinoma, run by Universität des Saarlandes at 10 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 15 inclusion and 31 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: under way, not looking for participants, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Event-free survival (EFS) rate (time frame: 2 years). 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 NCT05433116.

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 2 Dec 2025.

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