Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) vs. Standard Chemotherapy and Lenvatinib Monotherapy in Participants With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) That Progressed After Platinum Therapy and

This study will test the safety of the study drugs, lenvatinib alone, pembro and lenvatinib together, and standard chemotherapies alone in the treatment of HNSCC that has returned or spread after previous treatment. The study will potentially discover if participants who get pembro and lenvatinib for HNSCC that has returned or spread after previous treatment live longer than those who are treated with standard chemotherapies.

This study will measure what happens as lenvatinib goes through the body.

Some participants in this study will get pembro and lenvatinib together, some will receive lenvatinib alone. Getting pembro and lenvatinib together or getting lenvatinib alone is considered experimental, meaning the combination of pembro and lenvatinib or lenvatinib alone as used in this study is not approved by the U.S. Food and Drug Administration (FDA) for recurrent HNSCC.

This study will compare these experimental treatments with standard chemotherapy treatments for HNSCC that has returned or spread after previous treatment. These standard treatments are: docetaxel, paclitaxel, cetuximab, and capecitabine. The study drugs may be available by prescription for various cancers. They may not be approved for your exact type of cancer. The use of pembro and lenvatinib in this study is investigational.

Inova Schar Cancer Institute
8081 Innovation Park Dri.
Fairfax, VA 22031

A department of Inova Fairfax Hospital

• Adults over the age of 18
• 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 (eg, carboplatin or cisplatin) regimen with or without cetuximab
• Disease progression on or after treatment with an anti-PD-1/PD-L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies
  • Note: Eligible participants may have received anti-PD-1/PD-L1 mAb and platinum-containing therapy concomitantly
• Documentation of results from testing of HPV status for oropharyngeal cancer defined as p16 IHC testing using the CINtec® p16 Histology assay and a 70% cutoff point. If HPV status has previously been tested using this procedure, no retesting is required.
• 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 6 months after the last dose of docetaxel; no male contraception is needed for pembrolizumab and cetuximab. NOTE: If the contraception requirements in the local label for any of the study drugs is less stringent than the requirements above, the local label requirements should be followed
  
  Male participants agree to the following:
  
  Refrain from donating sperm PLUS either:
  
  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
   
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and is not a woman of childbearing potential (WOCBP) OR
  • Is a WOCBP randomized to pembrolizumab + lenvatinib (Arm 1) or lenvatinib monotherapy (Arm 3) and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with lower user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 5 during the intervention period and for at least 120 days post pembrolizumab or 1 month post lenvatinib, whichever occurs last
  • A WOCBP randomized to SOC chemotherapy is eligible to participate if she is using a contraceptive method that is highly effective with low user dependency or abstinent from heterosexual intercourse as her preferred and usual lifestyle and agrees 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. NOTE: If the contraception requirements in the local label for any of the study drugs is less stringent than the requirements above, the local label requirements should be followed.
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum; as required by local regulations) within 24 hours before the first dose of study intervention
• The participant (or legally acceptable representative if applicable) provides written informed consent for the study
• Have adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications for at least 1 week prior to randomization
• Additional eligibility information in protocol

• Women who are pregnant or breastfeeding
• Carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous histologies as primary tumors
• A history of re-irradiation to any head and neck sites of disease including the cervical, infraclavicular or supraclavicular lymph nodes for head and neck cancer
• Ulceration and/or fungation of disease onto the skin surface
• 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
• A known additional malignancy that is progressing or has required active systemic treatment within the past 3 years
  • Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded. Participants with low-risk early stage prostate cancer defined as follows are not excluded; Stage T1c or T2a with a Gleason score ≤ 6 and prostatic-specific antigen (PSA) <10 ng/mL either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study enrollment. Other exceptions may be considered.
• A known history of human immunodeficiency virus (HIV) infection
  • Note: No HIV testing is required unless mandated by local health authority
• A history of a gastrointestinal condition or procedure that, in the opinion of the investigator, may affect oral study drug absorption
• Active tuberculosis
• A history or current evidence of any condition, therapy, or laboratory abnormality that may 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, in the opinion of the treating investigator
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
• Additional ineligibility in protocol

Additional information can be found at: https://clinicaltrials.gov/ct2/show/NCT04428151