Clinical Trials /

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)

NCT04428151

Description:

This study is designed to assess the safety and efficacy of lenvatinib in combination with pembrolizumab versus standard of care (SOC) chemotherapy, and to also assess the safety and efficacy of lenvatinib monotherapy in participants with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) that have progressed after platinum therapy and a programmed cell death protein 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) inhibitor. The primary hypothesis is that pembrolizumab + lenvatinib is superior to SOC chemotherapy with respect to ORR per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review.

Related Conditions:
  • Hypopharyngeal Squamous Cell Carcinoma
  • Laryngeal Squamous Cell Carcinoma
  • Oral Cavity Squamous Cell Carcinoma
  • Oropharyngeal Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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)
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: 7902-009
  • SECONDARY ID: LEAP-009
  • SECONDARY ID: E7080-G000-228
  • SECONDARY ID: MK-7902-009
  • SECONDARY ID: 2019-000569-19
  • NCT ID: NCT04428151

Conditions

  • Squamous Cell Carcinoma of Head and Neck

Interventions

DrugSynonymsArms
PembrolizumabKEYTRUDA®, MK-3475, SCH 900475Pembrolizumab + Lenvatinib
LenvatinibLENVIMA®, MK-7902, E7080Pembrolizumab + Lenvatinib
DocetaxelTAXOTERE®SOC Chemotherapy
CapecitabineXeloda®SOC Chemotherapy
PaclitaxelTaxolSOC Chemotherapy
CetuximabERBITUX®SOC Chemotherapy
LenvatinibLENVIMA®, MK-7902, E7080Lenvatinib Monotherapy

Purpose

This study is designed to assess the safety and efficacy of lenvatinib in combination with pembrolizumab versus standard of care (SOC) chemotherapy, and to also assess the safety and efficacy of lenvatinib monotherapy in participants with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) that have progressed after platinum therapy and a programmed cell death protein 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) inhibitor. The primary hypothesis is that pembrolizumab + lenvatinib is superior to SOC chemotherapy with respect to ORR per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review.

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + LenvatinibExperimentalParticipants will be treated with the combination of pembrolizumab (200 mg 30-minute intravenous (IV) infusion on day 1 of each 21-day cycle for 35 cycles), plus lenvatinib (once daily 20 mg oral dose) 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.
  • Pembrolizumab
  • Lenvatinib
SOC ChemotherapyActive ComparatorParticipants 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.
  • Docetaxel
  • Capecitabine
  • Paclitaxel
  • Cetuximab
Lenvatinib MonotherapyActive ComparatorParticipants 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.
  • Lenvatinib

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  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 confirmed 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 30 days after the last dose of pembrolizumab
             + lenvatinib (Arm 1) or lenvatinib monotherapy (Arm 3), and 180 days after the last
             dose of standard of care (SOC) chemotherapy (Arm 2):

               -  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

               -  Agree to use a male condom when engaging in any activity that allows for passage
                  of ejaculate to another person of any sex

          -  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 30 days post lenvatinib, whichever occurs last
                  (Arms 1 and 3), or during the intervention period and for at least 180 days after
                  the last dose of SOC chemotherapy (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 180 days after
                  the last dose of SOC chemotherapy

          -  Adequately controlled blood pressure (BP) with or without antihypertensive medications

          -  Adequate organ function

        Exclusion Criteria:

          -  Carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous
             histologies as primary tumors

          -  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 that required systemic steroids, or 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

          -  History of hepatitis B or known active hepatitis C virus

          -  History of any contraindication or has a severe hypersensitivity to any components of
             pembrolizumab, lenvatinib or SOC chemotherapy

          -  Pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula

          -  History of a gastrointestinal condition or procedure that, in the opinion of the
             investigator, may 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 of
             study drug

          -  Active tuberculosis

          -  Difficulty swallowing capsules or ingesting a suspension either orally, by a
             nasogastric (NG) tube, or by a gastrostomy 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

          -  Received a live vaccine within 30 days of planned start of study intervention

          -  Previously treated with 4 or more systemic regimens given for recurrent/metastatic
             disease

          -  Currently participating in or has participated in a study of an investigational agent
             and received study therapy or used an investigational device within 4 weeks prior to
             the first dose of study intervention

          -  Known psychiatric or substance abuse disorder that would interfere with the
             participant's ability to cooperate with the requirements of the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Up to approximately 4 years
Safety Issue:
Description:ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of the diameters of target lesions) until progressive disease (PD) or death due to any cause, whichever occurs first. Responses are according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR).

Secondary Outcome Measures

Measure:Progression-Free Survival (PFS)
Time Frame:Up to approximately 4 years
Safety Issue:
Description:PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Responses are according to modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR).
Measure:Overall Survival (OS)
Time Frame:Up to approximately 4 years
Safety Issue:
Description:OS is defined as the time from randomization to death due to any cause.
Measure:Duration of Response (DOR)
Time Frame:Up to approximately 4 years
Safety Issue:
Description:DOR is defined as the time from the first documented evidence of complete response (CR: disappearance of all target lesions) or partial response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of the diameters of target lesions) until progressive disease (PD) or death due to any cause, whichever occurs first. Responses are according to modified RECIST 1.1 as assessed by BICR.
Measure:Number of Participants Who Experienced One or More Adverse Events (AEs)
Time Frame:Up to approximately 4 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.
Measure:Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE)
Time Frame:Up to approximately 4 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Death-Ligand 1 (PDL1, PD-L1)

Last Updated

July 23, 2020