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-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- 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 > o =1% of tumor cells (TPS>o =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 120 days after the last dose of study intervention:
- 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. Refrain from donating sperm for at least 120 days after the last dose of lenvatinib.
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 after the last dose of study intervention 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 72 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 representative if applicable) provides written informed consent/assent for the study.
12. Have adequately controlled blood pre
1Has known untreated central nervous system metastases and/or carcinomatous meningitis. Particip with prev treated brain metast may particip provided they are radiolog stable (ie, without evid of progression for at least4ws 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
2Has clinically signif hemoptysis (at least0.5teaspoon of bright red blood)or tumor bleeding within2ws before first dose of study interv
3Has Radiogr evid of encasement or invasion of a major blood vessel, or of intratumoral cavitation. The degree of tumor inva/infiltr of major blood vessels should be consid bec of the pot risk of sev hemorr ass with tumor shrinkage/necrosis after lenva therapy
4Has known hist of add malignancy, exc if particip has undergone potentially curat therapy with no evid of that disease recurr for at least3ys since init of that therapy
5Has active autoimm disease that has required syst treatm in past 2 y (use of disease-modifying agents, corticost or immunosuppr drugs).Replac therapy( thyroxine, insulin or physiologic corticost replacement ther for adrenal or pituitary insuff etc) isnt consid a form of syst treatm and is allowed
6Has had allogeneic tissue/solid organ transplant
7Has known history of HIV infection; HIV testing isnt requir unless mandated by local health authority
8Has hist of (noninfectious) pneumonitis that required syst ster or cur pneumonitis/interstitial lung disease
9Has known hist of hep B (defined as hepB surface antigen [HBsAg] react or hep B virus [HBV]-DNA detected) or known act hep C virus (HCV, defined as HCV-RNA [qualitative] detected or HCV antibody reactive, if HCV-RNA is not the local SOC) infect
10Has hist of gastroint condit or proced that in the opinion of investig may affect oral study drug absorption
11Has signif cardiovasc impairment within12months of first dose of study interv, such as hist of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocard infarct, cerebrovasc accid(CVA)/stroke, or card arrhyth assoc with hemodyn instab
12Hasnt recovered adeq from any tox and/or complications from major surgery bef starting ther
13Has known hist of act tuberc(TB)
14Has act infec requiring syst ther
15Has known psychiatric or subst abuse disorder that would interf with particip's cooperation for requirem of study
16Prev had sev hypers reac to treatm with mAb or known sensit or intoler to any component of lenva or pembro
17WOCBP who has pos urine pregn test within24h bef first dose of study interv
18Has received prior syst chemoth or other targeted or biolog antineopl therapy for metastatic NSCLC
19Has rec pr therapy with anti-PD-1, anti-PD-L1, or anti-PDL2 ag or agent direct to another stimulatory or coinhibitory T-cell rec( CTLA-4,OX 40,CD137)or has rec lenva as monoth or in comb with anti-PD-1 agents
20Has rec radioth within14d before first dose of study interv or lung radiation ther of >30Gy within6months bef first dose of st interv
21Has diagn of immunodef or is receiv any form of immunosuppr ther within7d bef first dose of study interv
22Is rec syst steroid therapy(doses exceeding10mg daily of prednisone equivalent)within7d bef first dose of study interv
23Has rec live vaccine within30d bef first dose of study interv
24Particips with proteinuria >1+on urine dipstick testing/urinalysis will undergo 24hour ur
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