A Phase 2, Randomized, Open-label, Three-arm Clinical Study to Evaluate the Safety and Efficacy of Lenvatinib (E7080/MK7902) in Combination with Pembrolizumab (MK3475) 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 (PD1/PDL1 Inhibitors) (LEAP009)

Cancer Categories

Head and Neck

Karmanos Trial ID

2020-062

NCT ID

NCT04428151

Age Group

Adult

Scope

National

Phase

Phase II

Principal Investigator

Ammar
Sukari, M.D.
Oncology - Medical View Profile

Objective:

Primary Objective:

to compare pembrolizumab + lenvatinib combination therapy and SOC chemotherapy with respect to ORR per RECIST 1.1 as assessed by BICR.

Secondary Objectives:

to compare pembrolizumab + lenvatinib combination therapy and SOC chemotherapy with respect to PFS per RECIST 1.1 by BICR.
to compare pembrolizumab + lenvatinib combination therapy and SOC chemotherapy with respect to OS.
to assess the efficacy of pembrolizumab + lenvatinib combination therapy and SOC chemotherapy with respect to DOR per RECIST 1.1, by BICR.
to assess the safety and tolerability of study intervention with pembrolizumab + lenvatinib combination therapy, SOC chemotherapy, and lenvatinib monotherapy

Request an Appointment

Refer a Patient

NCI Dictionary of Cancer Terms

KCI Clinical Trials App

Eligibility

Inclusion Criteria:

Pathologically 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 (e.g., 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 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
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 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 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 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 malabsorption or any other condition or procedure that 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
Has difficulty swallowing capsules or ingesting a suspension orally, or by a feeding 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. Participants with endocrine-related AEs Grade ≤2 requiring treatment or hormone replacement may be eligible
Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: Administration of killed vaccines is allowed
Previously treated with 4 or more systemic regimens given for recurrent/metastatic disease
Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study

Locations

Karmanos Cancer Institute - Detroit Headquarters

4100 John R
Detroit, MI 48201
Get Directions

Phone: 800-527-6266

Karmanos Cancer Institute at Weisberg Cancer Center - Farmington Hills

31995 Northwestern Hwy
Farmington Hills, MI 48334
Get Directions

Phone: 800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices