A Phase 2, Randomized, Open-label Three-arm Clinical Study to Evaluate the Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care Chemotherapy and Lenvatinib Monotherapy in Participants With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) That Have Progressed After Platinum Therapy and Immunotherapy (PD-1/PD-L1 Inhibitors) (LEAP-009)
Overview
- Phase
- Phase 2
- Intervention
- Lenvatinib
- Conditions
- Squamous Cell Carcinoma of Head and Neck
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 408
- Locations
- 120
- Primary Endpoint
- Overall Survival (OS)
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief 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.
Detailed Description
With Amendment 7, participants will discontinue lenvatinib and pembrolizumab and lenvatinib monotherapy, unless discussed with the Sponsor. A protocol-specified periodic safety review was completed with a data cut-off of 31-May-2024 (Primary Completion Date) and served as the final analysis of the primary outcome measure. Per protocol, 34 participants enrolled after the primary completion date and will be analyzed in the End of Trial analysis.
Investigators
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
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 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
Arms & Interventions
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.
Intervention: Lenvatinib
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.
Intervention: Pembrolizumab
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.
Intervention: Docetaxel
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.
Intervention: Capecitabine
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.
Intervention: Paclitaxel
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.
Intervention: Cetuximab
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.
Intervention: Lenvatinib
Outcomes
Primary Outcomes
Overall Survival (OS)
Time Frame: Up to approximately 45 months
OS was defined as the time from randomization to death due to any cause.
Secondary Outcomes
- Progression-Free Survival (PFS)(Up to approximately 45 months)
- Objective Response Rate (ORR)(Up to approximately 45 months)
- Duration of Response (DOR)(Up to approximately 45 months)
- Number of Participants Who Experienced One or More Adverse Events (AEs)(Up to approximately 5 years)
- Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)(Up to approximately 5 years)