Recurrent/metastatic head and neck squamous cell carcinoma MedDRA version: 22.0 Level: LLT Classification code 10082179 Term: Squamous cell carcinoma of head and neck metastatic System Organ Class: 100000004864
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: m
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female and at least 18 years of age on the day of providing informed consent 2. Have pathologically confirmed recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and/or larynx that is considered incurable by local therapies 3. Experienced disease progression at any time during or after treatment with a platinum-containing (eg, carboplatin or cisplatin) regimen with or without cetuximab 4. 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: - Treatment with an anti-PD-1/PD-L1 mAb - Received at least 2 doses of an anti-PD-1/PD-L1 mAb - 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. 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. 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. 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. Measurable disease by CT or MRI based on RECIST 1.1 as verified by BICR. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions 9. ECOG performance status of 0 or 1 assessed within 7 days of the first dose 10. 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. No male contraception is needed for pembrolizumab and cetuximab. - 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 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 lenvatinib + pembrolizumab (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 (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. - A WOCBP randomized to SOC chemotherapy is eligible to participate if she is using a contraceptive method that is highly effec
Exclusion criteria
Exclusion criteria: 1. Removed, redundant with Inclusion Criterion #2. 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/interstitial lung disease that required systemic steroids, or has 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. Removed, not relevant due to addition of Inclusion Criteria #15 and #16. 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 malabsorption or any other condition or procedure that 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 orally or by feeding tube 24. 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 25. Has had prior treatment with lenvatinib as monotherapy or in combination with an PD-1/PD-L1 inhibitor or other therapies 26. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to Study Day 1 or has not recovered from AEs due to a previously administered agent. Participants with endocrine-related AEs Grade =2 requiring treatment or hormone replacement may be eligible. 27. Has received a live o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare lenvatinib (MK-7902/E7080) + pembrolizumab (MK-3475) combination therapy and standard of care (SOC) chemotherapy with respect to objective response rate (ORR) per modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as assessed by blinded independent central review.;Secondary Objective: 1. To compare lenvatinib + pembrolizumab combination therapy and standard of care (SOC) chemotherapy with respect to progression-free survival (PFS) per modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as assessed by blinded independent central review. 2. To compare lenvatinib + pembrolizumab combination therapy and standard of care (SOC) chemotherapy with respect to overall survival (OS). 3. To compare lenvatinib + pembrolizumab combination therapy and standard of care (SOC) chemotherapy with respect to duration of response (DOR) per modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), as assessed by blinded independent central review. 4. To assess the safety and tolerability of lenvatinib + pembrolizumab combination therapy, standard of care (SOC) chemotherapy, and lenvatinib monotherapy. ;Primary end point(s): 1. Objective Response Rate (ORR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review;Timepoint(s) of evaluation of this end point: 1. Up to approximately 4 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-Free Survival (PFS) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review 2. Overall Survival (OS) 3. Duration of Response (DOR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Independent Central Review 4. Number of Participants Who Experienced One or More Adverse Events (AEs) 5. Number of Participants Who Discontinued Study Intervention Due to an Adverse Event (AE);Timepoint(s) of evaluation of this end point: 1. Up to approximately 4 years 2. Up to approximately 4 years 3. Up to approximately 4 years 4. Up to approximately 4 years 5. Up to approximately 4 years | — |
Countries
Australia, Canada, Denmark, France, Israel, Korea, Republic of, Norway, Portugal, Romania, Spain, Taiwan, United Kingdom, United States
Outcome results
None listed