A Phase 3 Study of Pembrolizumab with or without Lenvatinib in Metastatic NSCLC
- Conditions
- Metastatic non-small cell lung cancer (NSCLC)MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003794-98-HU
- 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
- 620
1. Have a histologically or cytologically confirmed diagnosis of NSCLC.
2. Have Stage IV NSCLC (American Joint Committee on Cancer [AJCC], version 8).
3. Have confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy (documentation of the absence of tumor-activating EGFR mutations [eg,
DEL19 or L858R], AND absence of ALK and ROS1 gene rearrangements OR presence of a Kirsten rat sarcoma [K-ras] mutation).
4. Have measurable disease based on RECIST 1.1, as determined by the local site.
5. Tumor tissue that demonstrates PD-L1 expression in =1% of tumor cells (TPS =1%) as assessed by IHC 22C3 pharmDx at a central laboratory.
6. Be = 18 years of age, inclusive, at the time of signing the ICF.
7. Have a life expectancy of at least 3 months.
8. Have an ECOG performance status of 0 or 1 within 7 days before the first dose of study intervention but before randomization.
Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Male Participants
9. 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/matching placebo:
- 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 (vasectomized or secondary to medical cause [Appendix 5]) as detailed below:
- Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant.
- Please note that 30 days after lenvatinib/matching placebo is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed.
Female Participants
10. 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 (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), as described in Appendix 5 during the intervention period and for at least 120 days post pembrolizumab or 30 days
post lenvatinib/matching placebo, whichever occurs last. The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention.
-A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours before the first dose of study intervention.
- If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
- Additional requirements for pregnancy testing during and after study intervention are located in Appendix 2.
- The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
11. The participant (or legally acceptable
1. Has known untreated central nervous system metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression for at least 4 weeks by repeat imaging (note: repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days before first dose of study intervention.
2. Has clinically significant hemoptysis (at least 0.5 teaspoon of bright red blood) or tumor bleeding within 2 weeks before the first dose of study intervention.
3. Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation. The degree of tumor invasion/infiltration of major blood vessels should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib therapy.
4. Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy.
5. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
6. Has had an allogeneic tissue/solid organ transplant.
7. Has a known history of human immunodeficiency virus (HIV) infection; HIV testing is not required unless mandated by the local health authority.
8. Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
9. Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive or hepatitis B virus [HBV]-DNA detected) or known active hepatitis C virus (HCV, defined as HCV-RNA [qualitative] detected or HCV antibody reactive, if HCV-RNA is not the local SOC) infection.
10. Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption.
11. Has significant cardiovascular impairment within 12 months of the first dose of study intervention, such as a history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability.
12. Has not recovered adequately from any toxicity and/or complications from major surgery before starting therapy.
13. Has a known history of active tuberculosis (TB).
14. Has an active infection requiring systemic therapy.
15. Has a known psychiatric or substance abuse disorder that would interfere with the participant’s cooperation for the requirements of the study.
16. Previously had a severe hypersensitivity reaction to treatment with an mAb or has a known sensitivity or intolerance to any component of lenvatinib or pembrolizumab.
17. WOCBP who has a positive urine pregnancy test within 24 hours before the first dose of study intervention.
18. Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC.
19. Has received prior therapy with an anti-PD-1, anti
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