Purpose

This study is designed to assess the safety and efficacy of lenvatinib in combination with pembrolizumab versus standard of care (SOC) chemotherapy, and to also assess the safety and efficacy of lenvatinib monotherapy in participants with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) that have progressed after platinum therapy and a programmed cell death protein 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) inhibitor. The primary hypothesis is that lenvatinib + pembrolizumab is superior to SOC chemotherapy with respect to ORR per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Histologically confirmed recurrent (not amenable to curative treatment with local and/or systemic therapies) or metastatic (disseminated) HNSCC of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies. - Disease progression at any time during or after treatment with a platinum-containing (e.g., carboplatin or cisplatin) regimen. - Disease progression on or after treatment with an anti-PD-1/PD-L1 mAb (programmed cell death protein 1/programmed death-ligand 1 monoclonal antibody). - Pre-study imaging that demonstrates evidence of disease progression based on investigator review of at least 2 pre-study images per RECIST 1.1, following initiation of treatment with a PD-1/PD-L1 inhibitor. - Measurable disease by CT or MRI based on Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as verified by blinded independent central review (BICR). Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. - ECOG performance status of 0 or 1 assessed within 7 days of the first dose of study intervention. - Male participants are eligible to participate if they agree to the following during the intervention period and for at least 1 week after the last dose of lenvatinib, 3 months after the last dose of capecitabine and paclitaxel, and and 6 months after the last dose of docetaxel: - Refrain from donating sperm - Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent; or must agree to use contraception unless confirmed to be azoospermic. - Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. - A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: - Is not a woman of childbearing potential (WOCBP) - Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab or 1 month post lenvatinib, whichever occurs last (Arms 1 and 3), or during the intervention period and for at least 6 months after the last dose of capecitabine, docetaxel, paclitaxel; and 2 months after the last dose of cetuximab (Arm 2). - Female participants who randomize to Arm 2 must also agree not to donate or freeze/store eggs during the intervention period and for at least 6 months after the last dose of capecitabine, docetaxel, paclitaxel; and 2 months after the last dose of cetuximab. - Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. - Adequately controlled blood pressure (BP) with or without antihypertensive medications. - Adequate organ function.

Exclusion Criteria

  • Carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous histologies as primary tumors. - Disease that is suitable for local therapy administered with curative intent. - Life expectancy of less than 3 months and/or has rapidly progressing disease in the opinion of the treating investigator. - History of (noninfectious) pneumonitis/interstitial lung disease that required steroids, or has current pneumonitis/interstitial lung disease. - Active infection requiring systemic therapy. - 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. - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. - Known additional malignancy that is progressing or has required active systemic treatment within the past 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ that have undergone potentially curative therapy. - Active autoimmune disease that has required systemic treatment in the past 2 years. - Had an allogeneic tissue/solid organ transplant. - Known history of human immunodeficiency virus (HIV) infection. - History of hepatitis B or known active hepatitis C virus. - History of any contraindication or has a severe hypersensitivity to any components of pembrolizumab, lenvatinib or SOC chemotherapy. - Pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula. - History of a gastrointestinal malabsorption or any other condition or procedure that may affect oral study drug absorption. - Had major surgery within 3 weeks prior to first dose of study interventions. - Clinically significant cardiovascular impairment within 12 months of the first dose of study drug. - Active tuberculosis. - Has difficulty swallowing capsules or ingesting a suspension orally, or by a feeding tube. - Prior treatment with lenvatinib. - Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Study Day 1 or has not recovered from adverse events (AEs) due to a previously administered agent. - Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Administration of killed vaccines is allowed. - Previously treated with 4 or more systemic regimens given for recurrent/metastatic disease. - Currently participating in or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study intervention. - Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Lenvatinib + Pembrolizumab
Participants will be treated with the combination of lenvatinib (once daily 20 mg oral dose) plus pembrolizumab (200 mg 30-minute intravenous (IV) infusion on Day 1 of each 21-day cycle for 35 cycles), until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met. Participants may receive up to an additional 17 cycles of pembrolizumab as Second Course treatment, with or without lenvatinib.
  • Drug: Lenvatinib
    20 mg once daily, taken as oral capsules
    Other names:
    • LENVIMA®
    • MK-7902
    • E7080
  • Biological: Pembrolizumab
    200 mg 30-minute IV infusion on day 1 of each 21-day cycle
    Other names:
    • KEYTRUDA®
    • MK-3475
    • SCH 900475
Active Comparator
SOC Chemotherapy
Participants will be treated with investigator's choice of standard of care (SOC) chemotherapy (docetaxel, paclitaxel, cetuximab, or capecitabine) until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met.
  • Drug: Docetaxel
    75 mg/m^2 administered as an IV infusion on day 1 of each 21-day cycle
    Other names:
    • TAXOTERE®
  • Drug: Capecitabine
    1250 mg/m^2 twice daily on days 1-14 of each 21-day cycle, taken as oral tablets
    Other names:
    • Xeloda®
  • Drug: Paclitaxel
    80 mg/m^2 administered as an IV infusion on days 1, 8, and 15 of each 21-day cycle
    Other names:
    • Taxol
  • Drug: Cetuximab
    400 mg/m^2 loading dose, followed by 250 mg/m^2 administered as an IV infusion on days 1, 8, and 15 of each 21-day cycle
    Other names:
    • ERBITUX®
Active Comparator
Lenvatinib Monotherapy
Participants will be treated with lenvatinib monotherapy (once daily 24 mg oral dose) until centrally verified disease progression, or until a protocol-specified discontinuation criterion is met.
  • Drug: Lenvatinib
    24 mg once daily, taken as oral capsules
    Other names:
    • LENVIMA®
    • MK-7902
    • E7080

Recruiting Locations

University of Kansas Cancer Center ( Site 1538)
Westwood, Kansas 66205
Contact:
Study Coordinator
913-588-1227

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme Corp.

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@merck.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.