NSCLC with squamous or nonsquamous histology MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK-3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Concentration unit: m
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Have a histologically or cytologically confirmed diagnosis of metastatic squamous or nonsquamous NSCLC 2. Have PD on treatment with one prior an anti-PD-1/PD-L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. Anti- PD-1/PD-L1 treatment progression is defined by meeting ALL of the following criteria: • Treatment with at least 2 doses of an anti-PD-1/PD-L1 mAb • PD after an anti-PD-1/PD-L1 mAb as defined by RECIST v1.1. Evidence of PD is defined as: - imaging prior to anti-PD-1/PD-L1 treatment or image showing nadir during anti-PD-1/PD-L1 treatment; AND - imaging to determine that radiographic progression has occurred per RECIST 1.1 within 12 weeks (84 days) from the last dose of an anti-PD-1/PD-L1 mAb. 3. Have PD during/after platinum doublet chemotherapy for metastatic disease. 4. Have confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy (documentation of absence of tumor-activating EGFR mutations [eg, DEL19 or L858R], and absence of ALK and ROS1 gene rearrangements OR presence of a K-ras mutation) 5. Have submitted prestudy imaging that confirmed evidence of PD based on investigator review of at least 2 images per RECIST 1.1, following initiation of an anti-PD-1/PD-L1 mAb 6. Have measurable disease based on RECIST 1.1 as determined by the local site assessment. • Have at least 1 measurable lesion by CT or MRI per RECIST 1.1 7. Have provided tumor tissue for PD-L1 biomarker analysis from an archival sample (defined as: from initial diagnosis of NSCLC and prior to receiving immunotherapy [antiPD-1/PD-L1], from the primary lesion or a metastatic lesion) 8. Have provided prior to randomization tissue from a newly obtained formalin-fixed sample from a new biopsy (defined as: after completion of immunotherapy [anti-PD-1/PD-L1] and before receiving a randomization number), of a tumor lesion not previously irradiated 9. Be =18 years of age on the day of providing documented informed consent 10. Have ECOG performance status of 0 or 1 within 7 days before the first dose of study intervention but before randomization 11. Have a life expectancy of at least 3 months 12. Male participants receiving pembrolizumab ± lenvatinib or lenvatinib are eligible to participate if they agree to the following during the intervention period or 7 days after the last dose of lenvatinib: Male participants randomized to docetaxel are eligible to participate if they agree to the following during the intervention period and for at least 180 days after the last dose of docetaxel: • 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) • 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 13. A female participant is eligible to participate if she is not pregnant or breastfeeding and at least 1 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 is abstinent from heterosexual intercourse as her preferred and usual lifestyle, during the intervention perio
Exclusion criteria
Exclusion criteria: 1. Has received docetaxel as monotherapy or in combination with other therapies 2. Has received lenvatinib as monotherapy or in combination with an anti-PD-1/PD-L1 mAb 3. Has received radiotherapy within 2 weeks before the first dose of study intervention or has received lung radiation therapy >30 Gy within 6 months before the first dose of study intervention 4. Has received a live vaccine within 30 days before the first dose of study intervention 5. 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 6. Has radiographic evidence of intratumoral cavitation, 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. 7. Has clinically significant cardiovascular impairment within 12 months of the first dose of study intervention, such as history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction or cerebrovascular accident/transient ischemic attack (TIA)/stroke, cardiac revascularization, or cardiac arrhythmia associated with hemodynamic instability 8. Has a history of a gastrointestinal condition or procedure that, in the opinion of the investigator, may affect oral study intervention absorption 9. Has a pre-existing =Grade 3 gastrointestinal or non-gastrointestinal fistula. 10. Is a WOCBP who has a positive urine pregnancy test within 24 hours or a positive serum pregnancy test within 72 hours before randomization 11. Is currently participating in a clinical trial and receiving study therapy or participated in a study of an investigational agent within 4 weeks of the first dose of study intervention 12. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (exceeding 10 mg of prednisone or equivalent daily) or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention 13. Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of disease recurrence for 3 years since initiation of that therapy 14. Has known active central nervous system metastases and/or carcinomatous meningitis 15. Has severe hypersensitivity (Grade =3) to pembrolizumab and/or any of its excipients 16. Has a sensitivity to any of the excipients contained in lenvatinib 17. Has a sensitivity to any of the excipients contained in docetaxel 18. 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) 19. Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease 20. Has an active infection requiring systemic therapy 21. Has a known history of human immunodeficiency virus (HIV) infection 22. Has a known history of hepatitis B (defined as hepatitis B surface antigen (HBsAg) reactive or known active hepatitis C virus (HCV) (defined as HCV RNA [qualitative] is detected) infection 23. Has a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To compare pembrolizumab (MK-3475) + lenvatinib (MK-7902) to docetaxel with respect to overall survival (OS) 2. To compare pembrolizumab + lenvatinib to docetaxel with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR) ;Secondary Objective: 1. To compare pembrolizumab + lenvatinib to docetaxel with respect to objective response rate (ORR) per RECIST 1.1 by BICR 2. To compare pembrolizumab + lenvatinib to lenvatinib monotherapy with respect to ORR per RECIST 1.1 by BICR 3. To assess duration of response (DOR) with pembrolizumab + lenvatinib and docetaxel per RECIST 1.1 by BICR 4. To assess the safety and tolerability of treatment with pembrolizumab + lenvatinib versus docetaxel 5. To assess the safety and tolerability of treatment with lenvatinib monotherapy 6. To compare pembrolizumab + lenvatinib to docetaxel with respect to the mean change from baseline in global health status/quality of life (QoL), cough, chest pain, dyspnea, and physical functioning 7. To compare pembrolizumab + lenvatinib to docetaxel with respect to time to true deterioration (TTD) in global health status/QoL, cough, chest pain, dyspnea, and physical functioning scales;Primary end point(s): 1. Overall Survival (OS) 2. Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) ;Timepoint(s) of evaluation of this end point: 1. Up to ~48 months 2. Up to ~36 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Docetaxel 2. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Lenvatinib Monotherapy 3. Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 4. Number of Participants Experiencing an Adverse Event (AE) 5. Number of Participants Discontinuing Study Treatment Due to an Adverse Event (AE) 6. Change from Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score 7. Change from Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 31) Scale Score 8. Change from Baseline in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score 9. Change from Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score 10. Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score 11. Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score 12. Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score 13. Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score 14. Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score 15. Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score ;Timepoint(s) of evaluation of this end point: 1. Up to ~18 months 2. Up to ~36 months 3. Up to ~48 months 4. Up to ~48 months 5. Up to ~48 months 6. Baseline and Week 12 7. Baseline and Week 12 8. Baseline and Week 12 9. Baseline and Week 12 10. Baseline and Week 12 11. Up to ~48 months 12. Up to ~48 months 13. Up to ~48 months 14. Up to ~48 m | — |
Countries
Argentina, Australia, Canada, Colombia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Portugal, Puerto Rico, Russian Federation, Spain, United Kingdom, United States
Outcome results
None listed