A PHASE 3 STUDY OF PEMBROLIZUMAB (MK-3475) WITH OR WITHOUT LENVATINIB (E7080/MK-7902) AS 1L INTERVENTION IN A PD-L1 SELECTED POPULATION WITH R/M HNSCC (LEAP-010)
- Conditions
- -C76 Malignant neoplasm of other and ill-defined sitesMalignant neoplasm of other and ill-defined sitesC76
- Registration Number
- PER-044-19
- Lead Sponsor
- Merck Sharp & Dohme Corp., una subsidiaria de Merck & Co. Inc.,
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 1
1. Has histologically confirmed diagnosis of R/M HNSCC that is considered incurable by local therapies
2. Has a primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx
3. Is male or female, and at least 18 years of age at the time of signing the informed consent
4. 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 lenvatinib/placebo:
-Be abstinent from heterosexual intercourse as their preferred and usual lifestyle
OR
-Must agree to use contraception
5. 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 and using a contraceptive method that is highly effective
6. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the study
7. Has measurable disease per RECIST 1.1 as assessed by BICR
8. Has provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. FFPE tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
9. Has a PD-L1 positive (CPS ≥1) tumor as determined by the central laboratory
10. Participants with oropharyngeal cancer must have results from testing of HPV status defined as p16 IHC testing using CINtec® p16 Histology assay and a 70% cutoff point. If HPV status was previously tested using this method, no additional testing is required
11. Has an ECOG performance score of 0 to 1
12. Has adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week prior to randomization
13. Has adequate organ function as defined in the following table (Table 3, see Protocol). Specimens must be collected within 7 days prior to the start of study intervention.
Please refer to the protocol for more information
1. Has histologically confirmed diagnosis of R/M HNSCC that is considered incurable by local therapies
2. Has a primary tumor location of oropharynx, oral cavity, hypopharynx, or larynx
3. Is male or female, and at least 18 years of age at the time of signing the informed consent
4. 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 lenvatinib/placebo:
-Be abstinent from heterosexual intercourse as their preferred and usual lifestyle
OR
-Must agree to use contraception
5. 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 and using a contraceptive method that is highly effective
6. The participant (or legally acceptable representative if applicable) provides written informed consent/assent for the study
7. Has measurable disease per RECIST 1.1 as assessed by BICR
8. Has provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. FFPE tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue
9. Has a PD-L1 positive (CPS ≥1) tumor as determined by the central laboratory
10. Participants with oropharyngeal cancer must have results from testing of HPV status defined as p16 IHC testing using CINtec® p16 Histology assay and a 70% cutoff point. If HPV status was previously tested using this method, no additional testing is required
11. Has an ECOG performance score of 0 to 1
12. Has adequately controlled BP with or without antihypertensive medications, defined as BP ≤150/90 mm Hg with no change in antihypertensive medications within 1 week prior to randomization
13. Has adequate organ function as defined in the following table (Table 3, see Protocol). Specimens must be collected within 7 days prior to the start of study intervention.
Please refer to the protocol for more information
Criterios de Exclusion claves (Ingles):
1. Has any evidence of symptoms or signs of active tumor bleeding within 6 months prior to randomization
2. Has radiographic evidence of major blood vessel invasion/infiltration or tumor demonstrates >90 degree abutment or encasement of a major blood vessel
3. 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
4. Has ulceration and/or fungation of disease onto the skin surface
5. Has a history of any contraindication or has a severe hypersensitivity to any components of pembrolizumab (≥Grade 3) or lenvatinib
6. Has pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
7. Has a history of a gastrointestinal condition or procedure that, in the opinion of the investigator, may affect oral study drug absorption
8. 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/TIA/stroke, cardiac revascularization, or cardiac arrhythmia associated with hemodynamic instability
9. Has disease that is suitable for local therapy administered with curative
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <br>Outcome name:Miettinen and Nurminen Method<br>Measure:Objective Response Rate (ORR) per RECIST 1.1 as assessed<br>by BICR.<br><br>Timepoints:The primary analysis will be conducted approximately 24 months after first Participant randomized.<br>;<br>Outcome name:Kaplan-Meier Method.<br>Measure:Overall survival (OS)<br>Timepoints:The two primary analysis will be conducted approximately 30 and 38 months after first<br>Participant randomized. The final analysis will be conducted approximately 44 months after first<br>Participant randomized<br>;<br>Outcome name:Kaplan-<br>Meier Method<br><br>Measure:Progression-free survival (PFS) per RECIST 1.1 as assessed<br>by BICR.<br><br>Timepoints:The primary analysis will be conducted approximately 24 months after first<br>Participant randomized. The final analysis will be conducted approximately 30 months after first<br>Participant randomized.<br>
- Secondary Outcome Measures
Name Time Method <br>Outcome name:Miettinen and Nurminen Method<br>Measure:Proportion of adverse events (AE) and Discontinuation of study intervention due to AEs<br>Timepoints:From study enrollment until resolution, stabilization, until the event is otherwise explained, or the participant is lost to follow-up<br>