Phase 2 N=374 Randomized Single-blind Treatment

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)

Squamous Cell Carcinoma of Head and Neck

Bottom Line

View on ClinicalTrials.gov: NCT04428151 ↗

Enrolled (actual)

374

Serious AEs

49.2%

Results posted

May 2025

Primary outcome: Primary: Overall Survival (OS) — 8.4; 11.3 Months — p=0.9963

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Lenvatinib (Drug); Pembrolizumab (Biological); Docetaxel (Drug); Capecitabine (Drug); Paclitaxel (Drug); Cetuximab (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Merck Sharp & Dohme LLC
Primary completion: May 2024

Outcome Measures

Outcome	Result	p-value
PRIMARY Overall Survival (OS)	8.4; 11.3	0.9963
SECONDARY Progression-Free Survival (PFS)	3.0; 2.8	0.4181
SECONDARY Objective Response Rate (ORR)	13.9; 20.4	0.9266219
SECONDARY Duration of Response (DOR)	4.1; 5.9	—
SECONDARY Number of Participants Who Experienced One or More Adverse Events (AEs)	—	—
SECONDARY Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)	—	—

Summary

Researchers are looking for new ways to treat people with head and neck cancer whose cancer has come back after treatment (recurrent) or whose cancer has spread to other parts of the body (metastatic). Some people with recurrent or metastatic head and neck cancer are treated with chemotherapy and immunotherapy, but the cancer gets worse. The goal of this study is to learn if more people who receive lenvatinib and pembrolizumab have a better overall survival rate than people who receive standard chemotherapy treatment.

Eligibility Criteria

Inclusion Criteria

Pathologically confirmed recurrent (not amenable to curative treatment with local and/or systemic therapies) or metastatic (disseminated) head and neck squamous cell carcinoma (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 a programmed cell death protein 1/programmed death-ligand 1 monoclonal antibody (anti-PD-1/PD-L1 mAb)
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 computed tomography scan (CT) or magnetic resonance imaging (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
Eastern Cooperative Oncology Group (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 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
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
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 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 excee

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04428151). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.