A Phase 2 study of lenvatinib (E7080/MK-7902) with pembrolizumab (MK-3475) versus standard of care chemotherapy and lenvatinib monotherapy for recurrent/metastatic head and neck squamous cell carcinoma that has progressed after platinum therapy and immunotherapy (LEAP-009)
- Conditions
- Recurrent/metastatic head and neck squamous cell carcinomaMedDRA version: 22.0Level: LLTClassification code 10082179Term: Squamous cell carcinoma of head and neck metastaticSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-000569-19-FR
- Lead Sponsor
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 400
1. Be male or female and at least 18 years of age on the day of signing informed consent
2. Have 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
3. Have experienced disease progression at any time during or after treatment with a platinum-containing (eg, carboplatin or cisplatin) regimen with or without cetuximab
4. Have disease progression on or after treatment with an anti-PD-1/PD-L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. Anti-PD-1/PD-L1 treatment progression is defined by meeting all the following criteria:
- Most recent treatment with an anti-PD-1/PD-L1 mAb
- Has received at least 2 doses of an anti-PD-1/PD-L1 mAb
- Has demonstrated disease progression on or after an anti-PD-1/PD-L1 mAb as defined by RECIST 1.1
- Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/PD-L1 mAb
5. Have submitted 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
6. Have documentation of results from testing of HPV status for oropharyngeal cancer defined as p16 IHC testing using the CINtec® p16 Histology assay and a 70% cutoff point. If HPV status has previously been tested using this procedure, no retesting is required
7. Have provided tissue for PD-L1 biomarker analysis from a core or excisional biopsy (fine needle aspirate is not adequate) not previously irradiated. Repeat samples may be required if adequate tissue is not provided. A newly obtained biopsy (within 90 days prior to start of study treatment) is strongly preferred, but an archival sample is acceptable
8. Have measurable disease by CT or MRI based on RECIST 1.1 as confirmed by BICR. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
9. Have an ECOG performance status of 0 or 1 assessed within 7 days of the first dose of study intervention
10. 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 SOC chemotherapy (Arm 2), and agree to the following:
- Refrain from donating sperm
PLUS either:
- 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
- Male participants must also agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person of any sex
11. 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 WOCBP
OR
- Is a WOCBP randomized to pembrolizumab + lenvatinib (Arm 1) or lenvatinib monotherapy (Arm 3) and using a contraceptive method that is highly effective (with a failure rate of <1% per year), with lower user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abst
1. Has carcinoma of the nasopharynx, salivary gland, unknown primary origin, or nonsquamous histologies as primary tumors
2. 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
3. Has disease that is suitable for local therapy administered with curative intent
4. Has a life expectancy of less than 3 months and/or has rapidly progressing disease, in the opinion of the treating investigator
5. Has any evidence of symptoms or signs of active tumor bleeding within 6 months prior to randomization
6. Has ulceration and/or fungation of disease onto the skin surface
7. Has radiographic evidence of major blood vessel invasion/infiltration or tumor demonstrates >90 degree abutment or encasement of a major blood vessel
8. Has a history of (noninfectious) pneumonitis that required systemic steroids, or current pneumonitis/interstitial lung disease
9. Has an active infection requiring systemic therapy
10. 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 to the first dose of study drug
11. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
12. Has a known additional malignancy that is progressing or has required active systemic treatment within the past 3 years
13. Has an active autoimmune disease that has required systemic treatment in the past 2 years
14. Has had an allogeneic tissue/solid organ transplant
15. Has a known history of HIV infection
16. Has a known history of hepatitis B or known active hepatitis C virus infection
17. Has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab (=Grade 3), lenvatinib or SOC chemotherapy
18. Has pre-existing =Grade 3 gastrointestinal or non-gastrointestinal fistula
19. Has a history of a gastrointestinal condition or procedure that, in the opinion of the investigator, may affect oral study drug absorption
20. Has had major surgery within 3 weeks prior to first dose of study interventions
21. Has clinically significant cardiovascular impairment within 12 months of the first dose of study drug, such as history of congestive heart failure greater than NYHA Class II, unstable angina, myocardial infarction or cerebrovascular accident /transient ischemic attack /stroke, cardiac revascularization, or cardiac arrhythmia associated with hemodynamic instability
22. Has active tuberculosis
23. Has difficulty swallowing capsules or ingesting a suspension either orally, by a nasogastric tube, or by a gastrostomy tube
24. 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 pembrolizumab + lenvatinib (Arm 1) or lenvatinib monotherapy (Arm 3) or 180 days after the last dose of SOC chemotherapy
25. Patients previously treated to one of the 4 SOC agents in this trialmay not receive the same agent if randomized to the SOC chemotherapy arm
26. Has had prior treatment with lenvati
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method