|
|
Pathologically 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 |
|
|
|
|
|
Is not a woman of childbearing potential (WOCBP) |
|
|
|
|
|
breastfeeding, and at least one of the following conditions applies |
|
|
|
|
|
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 |
|
|
|
|
|
Adequate organ function |
|
|
|
|
|
Adequately controlled blood pressure (BP) with or without antihypertensive medications |
|
|
|
|
|
Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization |
|
|
|
|
|
Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening |
|
|
|
|
|
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
|
|
|
|
|
|
Active infection requiring systemic therapy
|
|
|
|
|
|
History of (noninfectious) pneumonitis/interstitial lung disease that required steroids, or has current pneumonitis/interstitial lung disease
|
|
|
|
|
|
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 any contraindication or has a severe hypersensitivity to any components of pembrolizumab, lenvatinib or SOC chemotherapy
|
|
|
|
|
|
Had major surgery within 3 weeks prior to first dose of study interventions
|
|
|
|
|
|
History of a gastrointestinal malabsorption or any other condition or procedure that may affect oral study drug absorption
|
|
|
|
|
|
Pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
|
|
|
|
|
|
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. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible
|
|
|
|
|
|
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
|
|
|
|
|
|
Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
|
|
|
|
|
|
Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
|
|
|
|