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 That Progressed After Platinum Therapy and Immunotherapy (MK-7902-009/E7080-G000-228/LEAP-009)
J
Jonathan L. Berkowitz, MD, PhD
Primary Investigator
Administratively Closed
18 years or above
All
Phase
2
400 participants needed
1 Location
Brief description of study
This study is designed to assess the safety and efficacy of lenvatinib in combination withbrolizumab versus standard of care (SOC) chemotherapy, and to also assess the safety andy of lenvatinib monotherapy in participants with recurrent/metastatic head and neckquamous cell carcinoma (R/M HNSCC) that have progressed after platinum therapy and agrammed 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 asd by blinded independent central review.
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Squamous Cell Carcinoma of Head and Neck
-
Age: 18 years or above
-
Gender: All
Inclusion Criteria:
- Pathologically confirmed recurrent (not amenable to curative treatment with locald/or systemic therapies) or metastatic (disseminated) HNSCC of the oral cavity,harynx, 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 celldeath protein 1/programmed death-ligand 1 monoclonal antibody)
- Pre-study imaging that demonstrates evidence of disease progression based onvestigator review of at least 2 pre-study images per RECIST 1.1, followingwith 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 lesionsuated in a previously irradiated area are considered measurable if progression hasbeen demonstrated in such lesions
- ECOG performance status of 0 or 1 assessed within 7 days of the first dose of studyvention
- Male participants are eligible to participate if they agree to the following duringhe intervention period and for at least 1 week after the last dose of lenvatinib, 3hs after the last dose of capecitabine and paclitaxel, and and 6 months after thedose 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; orust agree to use contraception unless confirmed to be azoospermic
- Contraceptive use by men should be consistent with local regulations regardinghe 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 aure rate of <1% per year), with low user dependency or be abstinent fromheterosexual intercourse as their preferred and usual lifestyle (abstinent on ag term and persistent basis), during the intervention period and for at least120 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 afterhe last dose of capecitabine, docetaxel, paclitaxel; and 2 months after the lastdose of cetuximab (Arm 2)
- Female participants who randomize to Arm 2 must also agree not to donate orze/store eggs during the intervention period and for at least 6 months afterhe last dose of capecitabine, docetaxel, paclitaxel; and 2 months after the lastdose of cetuximab
- Adequately controlled blood pressure (BP) with or without antihypertensive medications
- Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if theyhave received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and haveundetectable HBV viral load prior to randomization
- Participants with history of hepatitis C virus (HCV) infection are eligible if HCVviral load is undetectable at screening
- Adequate organ function
Exclusion Criteria:
- 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 thehe treating investigator
- History of (noninfectious) pneumonitis/interstitial lung disease that requiredds, or has current pneumonitis/interstitial lung disease
- Active infection requiring systemic therapy
- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (indosing exceeding 10 mg daily of prednisone equivalent) or any other form ofunosuppressive 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 systemicwithin the past 3 years, except basal cell carcinoma of the skin, squamoushe skin, superficial bladder cancer, or carcinoma in situ that haveundergone 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 ofbrolizumab, lenvatinib or SOC chemotherapy.
- Pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
- History of a gastrointestinal malabsorption or any other condition or procedure thaty 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 ofudy drug
- Active tuberculosis
- Has difficulty swallowing capsules or ingesting a suspension orally, or by a feedingube
- Prior treatment with lenvatinib
- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2weeks prior to Study Day 1 or has not recovered from adverse events (AEs) due to aviously administered agent. Participants with endocrine-related AEs Grade ≤2quiring treatment or hormone replacement may be eligible
- Has received a live or live attenuated vaccine within 30 days prior to the first doseudy intervention. Note: Administration of killed vaccines is allowed
- Previously treated with 4 or more systemic regimens given for recurrent/metastaticdisease
- Has received an investigational agent or has used an investigational device within 4weeks prior to study intervention administration
- Known psychiatric or substance abuse disorder that would interfere with thebility to cooperate with the requirements of the study
Updated on
13 Dec 2024.
Study ID: 7902-009, BALL-MERCK-MK-7902, 1998737-1
