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: 20.0 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0 Level: LLT Classification code 10079440 Term: Non-squamous non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003824-35-ES
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- 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 based on RECIST 1.1.
4. Have provided an evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (that was not previously irradiated) for central PD L1 testing. Formalin fixed, paraffin embedded (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. A male participant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 120 days after the last dose of pembrolizumab and/or lenvatinib/matching placebo and up to 180 days after the last dose of chemotherapeutic agents.
A male participant must also agree to the following:
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.
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 woman of childbearing potential (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 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
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 major blood vessel invasion/infiltration. 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 treatment with lenvatinib.
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.
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 not recovered adequately from any toxicity and/or complication from major surgery prior to the first dose of study intervention.
16. Has known psychiatric or substance abuse disorders
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