Pembrolizumab and Lenvatinib After Definitive Chemoradiation of Locally Advanced HNSCC

NCT05433116 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: PeLeRad2021-004388-28
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 10

Brief 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).

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (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.

  2 years

Secondary Outcomes (3)

• Event-free survival (EFS) (continuous)

  2 years

• Locoregional control

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

• Toxicity of Pembrolizumab/lenvatinib

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

Study Arms (2)

pembrolizumab + lenvatinib

OTHER

combined pembrolizumab (200mg q3w) and lenvatinib treatment (20mg once daily)

Drug: Pembrolizumab; Drug: Lenvatinib

pembrolizumab

OTHER

pembrolizumab (200mg q3w)

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

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

Also known as: Keytruda

pembrolizumab; pembrolizumab + lenvatinib

Lenvatinib DRUG

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

Also known as: Lenvima

pembrolizumab + lenvatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.)
• 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.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• 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).
• 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.

Sponsors & Collaborators

• Universität des Saarlandes: lead

Study Sites (10)

University Hospital Ulm, Otolaryngology & Head and Neck Surgery

Ulm, Baden-Wurttemberg, 89070, Germany

Location

University Hospital Augsburg, Radiation Oncology

Augsburg, Bavaria, 86156, Germany

Location

University Hospital Erlangen, Radiation Oncology

Erlangen, Bavaria, 91054, Germany

Location

University Hospital Regensburg, Clinic and Polyclinic for Radiotherapy

Regensburg, Bavaria, 93053, Germany

Location

University Hospital Frankfurt/M, Center for Radiology

Frankfurt am Main, Hesse, 60590, Germany

Location

University Hospital Giessen; Ear, nose and throat clinic

Giessen, Hesse, 35392, Germany

Location

University Hospital Düsseldorf, Radiation Oncology

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

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

Homburg, Saarland, 66421, Germany

Location

Hospital Chemnitz, Radiation Oncology

Chemnitz, Saxony, 09116, Germany

Location

Gemeinschaftspraxis Hämatologie-Onkologie

Dresden, Saxony, 01307, Germany

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Study Officials

• Markus Hecht, Prof.

  Saarland University Medical Center, Clinic for Radiotherapy and Radiooncology

  PRINCIPAL INVESTIGATOR

• Antoniu-Oreste Gostian, Prof.

  University Hospital Straubing, Clinic for Otolaryngology, Head and Neck and Facial Plastic Surgery

  STUDY CHAIR

• Henning Kahl, MD

  University Hospital Augsburg, Radiation Oncology

  STUDY CHAIR

• Rainer Fietkau, Prof.

  University Hospital Erlangen, Radiation Oncology

  STUDY CHAIR

• Udo Gaipl, Prof.

  University Hospital Erlangen, Radiation Oncology

  STUDY CHAIR

• Markus Eckstein, MD

  University Hospital Erlangen, Pathology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2022
• First Posted: June 27, 2022
• Study Start: May 25, 2023
• Primary Completion: January 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: December 2, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

DE (10)