A Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First Line (1L) Intervention in a Programmed Cell Death-ligand 1 (PD-L1) Selected Population With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (LEAP-010) (MK-7902-010)-China Extension Study

Head and Neck Squamous Cell Carcinoma Clinical Trial

Official title:

A Phase 3, Randomized, Placebo-controlled, Double-blind Clinical Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) to Evaluate the Safety and Efficacy of Pembrolizumab and Lenvatinib as 1L Intervention in a PD-L1 Selected Population of Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC) (LEAP-010).

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05523323
• Other study ID #: 7902-010 China Extension
• Secondary ID: MK-7902-010 Chin
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 30, 2020
• Est. completion date: March 1, 2025

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study of pembrolizumab (MK-3475) with or without lenvatinib (E7080/MK-7902) as a first line intervention in a PD-L1 selected population with participants with recurrent or metastatic head and neck squamous cell carcinoma.

Hypotheses include:

• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR.

• Pembrolizumab + lenvatinib is superior to pembrolizumab + placebo with respect to overall survival (OS).

Description:

The MK-7902-010-China Extension Study will include participants previously enrolled in China in the global study for MK-7902-010 (NCT04199104) plus those enrolled during the China extension enrollment period.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 112
• Est. completion date: March 1, 2025
• Est. primary completion date: August 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has histologically confirmed diagnosis of R/M HNSCC that is considered incurable by local therapies.

Note: Participants with newly-diagnosed HNSCC must be M1/Stage IV.

• Has a primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx.

Note: Primary tumor site of nasopharynx (any histology) or unknown primary tumor (including p16+ unknown primary) are not eligible.

Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.

• Male participants agree to use approved contraception during the treatment period for at least 7 days after the last dose of lenvatinib/placebo, or refrain from heterosexual intercourse during this period

• Female participants are not pregnant or breastfeeding, and are not a woman of childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during the treatment period (or 14 days prior to the initiation of study treatment for oral contraception) and for at least 120 days post pembrolizumab, or 30 days post lenvatinib/placebo, whichever occurs last

• Has measurable disease per RECIST 1.1 as assessed by BICR. Note: Lesions situated in a previously irradiated area are considered measurable if progression has been showed in such lesions.

• Participants with oropharyngeal cancer must have results from testing of human papillomavirus HPV status.

• Has an Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 1.

• Has adequately controlled blood pressure with or without antihypertensive medications.

• Has adequate organ function.

Exclusion Criteria:

• Has any evidence of symptoms or signs of active tumor bleeding within 6 months before randomization.

• Has radiographic evidence of major blood vessel invasion/infiltration or tumor demonstrates >90 degree abutment or encasement of a major blood vessel.

Note: The degree of proximity to major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy.

• Has a history of re-irradiation to any head and neck sites of disease including the cervical, infraclavicular or supraclavicular lymph nodes for head and neck cancer.

• Has ulceration and/or fungation of disease onto the skin surface.

• Has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab (=Grade 3) or lenvatinib.

• Has pre-existing =Grade 3 gastrointestinal or non-gastrointestinal fistula.

• Has a history of a gastrointestinal condition or procedure that, in the opinion of the investigator, may affect oral study drug absorption.

• Has clinically significant cardiovascular impairment within 12 months of the first dose of study intervention, such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident/transient ischemic attack (TIA)/stroke, cardiac revascularization, or cardiac arrhythmia associated with hemodynamic instability.

• Has disease that is suitable for local therapy administered with curative intent.

• Had PD within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC.

• Has had major surgery within 3 weeks before to first dose of study interventions.

• Has difficulty swallowing capsules or ingesting a suspension orally or by a feeding tube.

• Has received prior therapy with lenvatinib or pembrolizumab.

• Received last dose of systemic therapy for locoregionally advanced disease less than 6 months before signing consent.

• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).

• Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.

• Has received prior radiotherapy within 2 weeks of start of study intervention.

• Has received a live vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.

• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention-administration.

• Has a 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 the first dose of study intervention.

• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.

Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g., breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

• Has an active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid) is allowed.

• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.

• Has an active infection requiring systemic therapy. (e.g., tuberculosis, known viral or bacterial infections, etc.).

• Has a known history of human immunodeficiency virus (HIV) infection.

• Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV ribonucleic acid (RNA) [qualitative] is detected) infection.

• Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention.

• Has had an allogenic tissue/solid organ transplant.

• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

Intervention

Drug:
• Lenvatinib
Lenvatinib, 20 mg (two 10-mg oral capsules) administered QD
• Pembrolizumab
Pembrolizumab (MK-3475), 200 mg, every 3 weeks (Q3W) by intravenous (IV) infusion for up to 35 3-week cycles
• Placebo
Lenvatinib-matching placebo, oral capsules, administered once daily (QD)

Locations

Country	Name	City	State
China	Beijing Tongren Hospital affiliated to Capital Medical University ( Site 3343)	Beijing	Beijing
China	Beijing Cancer Hospital ( Site 3314)	Beining	Beijing
China	Peking Union Medical College Hospital ( Site 3304)	Bejiing	Beijing
China	Jilin Cancer Hospital ( Site 3310)	Changchun	Jilin
China	Hunan Cancer Hospital ( Site 3311)	Changsha	Hunan
China	Hunan Cancer Hospital ( Site 3334)	Changsha	Hunan
China	Xiangya Hospital of Central South University ( Site 3305)	Changsha	Hunan
China	Changzhou Tumor Hospital - Changzhou Fourth People's Hospital ( Site 3339)	Changzhou	Jiangsu
China	West China Hospital of Sichuan University ( Site 3308)	Chengdu	Sichuan
China	Chongqing Cancer Hospital ( Site 3327)	Chongqing	Chongqing
China	Fujian Provincial Cancer Hospital ( Site 3326)	Fuzhou	Fujian
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University ( Site 3336)	Guangzhou	Guangdong
China	Sun Yat-sen Memorial Hospital, Sun Yat-sen University ( Site 3338)	Guangzhou	Guangdong
China	The First Affiliated Hospital, Sun Yat-sen University ( Site 3344)	Guangzhou	Guangdong
China	Guizhou Cancer Hospital ( Site 3330)	Guiyang	Guizhou
China	Zhejiang Cancer Hospital ( Site 3303)	Hangzhou	Zhejiang
China	The Third Affiliated Hospital of Harbin Medical University ( Site 3302)	Harbin	Heilongjiang
China	Anhui Cancer Hospital-Radiology Department ( Site 3333)	Hefei	Anhui
China	Jiangxi Cancer Hospital ( Site 3313)	Nanchang	Jiangxi
China	Guangxi Medical University Affiliated Tumor Hospital ( Site 3322)	Nanning	Guangxi
China	Fudan University Shanghai Cancer Center ( Site 3324)	Shanghai	Shanghai
China	Shanghai 9th People hospital ( Site 3332)	Shanghai	Shanghai
China	Shanghai East Hospital ( Site 3300)	Shanghai	Shanghai
China	Tianjin Medical University Cancer Hospital ( Site 3312)	Tianjin	Tianjin
China	Tongji Hospital Tongji Medical,Science & Technology ( Site 3316)	Wuhan	Hubei
China	Wuhan Union hospital Cancer Center ( Site 3307)	Wuhan	Hubei
China	The First Affiliated Hospital of Xi an Jiaotong University ( Site 3328)	XI An	Shaanxi
China	Henan Cancer Hospital ( Site 3309)	Zhengzhou	Henan

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR).	ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The percentage of participants who experience a CR or PR based on modified RECIST 1.1 will be presented.	Up to approximately 24 months
Primary	Progression Free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR).	PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as =20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of =5 mm. Note: The appearance of one or more new lesions is also considered PD.	Up to approximately 30 months
Primary	Overall Survival (OS)	OS is the time from randomization to death due to any cause.	Up to approximately 44 months
Secondary	Duration of Response (DOR)	For participants who demonstrate a confirmed complete response (CR: Disappearance of all target lesions) or confirmed Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death.	Up to approximately 44 months
Secondary	Number of Participants Who Experienced an Adverse Event (AE)	An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 44 months
Secondary	Number of Participants Who Discontinued Study Drug Due to an AE	An adverse event (AE) is defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it is considered related to the medical treatment or procedure, that occurs during the course of the study.	Up to approximately 44 months

External Links

•   Merck Clinical Trials Information