A Phase 3 Study of Pemetrexed + Platinum Chemotherapy + Pembrolizumab with or without Lenvatinib in Participants with NSCLC
- Conditions
- Metastatic Nonsquamous Non-small Cell Lung CancerMedDRA version: 27.0Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10079440Term: Non-squamous non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003824-35-PL
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 714
Participant must:
1. Have a histologically or cytologically confirmed diagnosis of Stage IV
(American Joint Committee on Cancer [AJCC], version 8 or current
version) nonsquamous NSCLC.
2. Have confirmation that EGFR , ALK , or ROS1 directed therapy is not
indicated as primary treatment (documentation of absence of tumor
activating EGFR mutations AND absence of ALK and ROS1 gene
rearrangements OR presence of a KRAS mutation).
3. Have measurable disease per RECIST 1.1.
4. Have provided 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. Formalin fixed specimens after the participant has been
diagnosed with metastatic disease are preferred. Biopsies obtained prior
to receipt of adjuvant/neoadjuvant chemotherapy are permitted if
recent biopsy is not feasible.
5. Be male or female =18 years of age inclusive, at the time of signing
the informed consent form (ICF).
6. Have a life expectancy of at least 3 months.
7. Have an ECOG performance status of 0 or 1 within 7 days prior to the
first dose of study intervention but before randomization.
8. Male participants are eligible to participate if they agree to the
following during the intervention period and for at least 7 days after the
last dose of lenvatinib/matching placebo and up to 180 days after the
last dose of chemotherapeutic agents:
• 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
(vasectomized or secondary to medical cause) as detailed below:
- Agree to use a male condom plus partner use of an additional
contraceptive method when having penile-vaginal intercourse with a
WOCBP who is not currently pregnant. Note: Men with a pregnant or
breastfeeding partner must agree to remain abstinent from penilevaginal
intercourse or use a male condom during each episode of penilevaginal
penetration.
9. 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), during the
intervention period and for at least 120 days post pembrolizumab and 30
days post-lenvatinib/matching placebo, and up to 180 days post last
dose of chemotherapeutic agents, 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.
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- 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.
10. The participant (or legally acceptable representative)
If participant:
1. Has known untreated central nervous system (CNS) 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 [the repeat imaging must be performed during the screening
period]), clinically stable, and have not required steroids for at least 14
days prior to the first dose of study intervention.
2. Has a history of (noninfectious) pneumonitis that required systemic
steroids or current pneumonitis/interstitial lung disease.
3. Radiographic evidence of intratumoral caviations, encasement, or
invasion of a major blood vessel. Additionally, the degree of proximity to
major blood vessels should be considered for exclusion because of the
potential risk of severe hemorrhage associated with tumor
shrinkage/necrosis after lenvatinib therapy. (In the chest, major blood
vessels include the main pulmonary artery, the left and right pulmonary
arteries, the 4 major pulmonary veins, the superior or inferior vena cava,
and the aorta).
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 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 allowed.
6. Has a diagnosis of immunodeficiency or is receiving chronic systemic
steroid therapy (doses exceeding 10 mg daily of prednisone equivalent)
or any other form of immunosuppressive therapy within 7 days prior the
first dose of study intervention.
7. Has had an allogeneic tissue/solid organ transplant.
8. Has a known history of human immunodeficiency virus (HIV)
infection. HIV testing is not required unless mandated by the local health
authority.
9. Has a known history of Hepatitis B (defined as Hepatitis B surface
antigen [HBsAg] reactive or HBV DNA detected) or known active
Hepatitis C virus (defined as HCV RNA [qualitative] detected or HCV
antibody reactive, if HCV RNA is not the local SOC) infection. No testing
for Hepatitis B or Hepatitis C is required unless mandated by the local
health authority.
10. Has a history of a gastrointestinal condition or procedure that in the
opinion of the investigator may affect oral drug absorption.
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11. Has active hemoptysis (at least 0.5 tsp of bright red blood) within 2
weeks prior to the first dose of study intervention.
12. Has significant cardiovascular impairment within 12 months prior to
the first dose of study intervention, including history of congestive heart
failure greater than New York Heart Association (NYHA) Class II,
unstable angina, myocardial infarction, cerebrovascular accident
(CVA)/stroke, or cardiac arrhythmia associated with hemodynamic
instability.
13. Has a known history of active tuberculosis.
14. Has an active infection requiring systemic therapy.
15. Has had major surgery within 3 weeks prior to first dose of study
interventions.
16. Has known psychiatric or substance abuse disorders that would
interfere with the participant's cooperation to meet with the
requirements
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