2022-501439-18-00
Completed
Phase 3
A Phase 3, multicenter, randomized, open-label trial to compare the efficacy and safety of pembrolizumab (MK-3475) in combination with lenvatinib (E7080/MK-7902) versus docetaxel in previously treated participants with metastatic non-small cell lung cancer (NSCLC) and progressive disease (PD) after platinum doublet chemotherapy and immunotherapy (LEAP-008)
Merck Sharp & Dohme LLC38 sites in 7 countries206 target enrollmentStarted: June 29, 2023Last updated:
Overview
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 206
- Locations
- 38
- Primary Endpoint
- Overall Survival (OS)
Overview
Brief Summary
- To compare pembrolizumab (MK-3475) + lenvatinib (MK-7902) to docetaxel with respect to overall survival (OS)
- 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)
Eligibility Criteria
- Ages
- 18 years to 65+ years (18-64 Years, 65+ Years)
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Has a histologically or cytologically confirmed diagnosis of metastatic squamous or nonsquamous NSCLC (Stage IV: M1a, M1b, M1c).
- •Has a life expectancy of at least 3 months
- •Male participants receiving pembrolizumab ± lenvatinib or lenvatinib must agree to refrain from donating sperm, and either 1) be abstinent from heterosexual intercourse; or 2) follow contraceptive guidance during the treatment period or 7 days after the last dose of lenvatinib. Male participants receiving docetaxel agree to adhere to the same conditions during the treatment period and for ≥90 days after the last dose of study treatment. Contraceptive use should either follow the study requirements or the local regulations for the study interventions, whichever is more stringent.
- •Female participants must not be pregnant, not be breastfeeding, and not be a woman of child-bearing potential (WOCBP). If a WOCBP, agrees to not donate eggs and either use contraception, or be abstinent from heterosexual intercourse during the treatment period and for ≥120 days after the last dose of pembrolizumab or 30 days after the last dose of lenvatinib, whichever occurs last. If a WOCBP receiving docetaxel, agrees to adhere to the same conditions during the treatment period and for ≥30 days after the last dose of study treatment. Contraception use should either follow the study requirements or the local regulations for the study interventions, whichever is more stringent.
- •Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week before randomization
- •If participant received major surgery or radiation therapy of >30 Gy, they have recovered from the toxicity and/or complications from the intervention.
- •Has adequate organ function.
- •Has PD on treatment with one prior anti-PD-1/PD-L1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. Retreatment with the same anti-PD-L1/PD-L1 mAb is acceptable in the overall course of treatment.
- •Has PD during/after platinum doublet chemotherapy for metastatic disease.
- •Has 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).
Exclusion Criteria
- •Has received docetaxel as monotherapy or in combination with other therapies.
- •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 treatment.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment.
- •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.
- •Has known active central nervous system metastases and/or carcinomatous meningitis.
- •Has severe hypersensitivity to pembrolizumab and/or any of its excipients.
- •Has a sensitivity to any of the excipients contained in lenvatinib and/or docetaxel.
- •Has an active autoimmune disease that has required systemic treatment in the past 2 years.
- •Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
- •Has an active infection requiring systemic therapy.
Outcomes
Primary Outcomes
Overall Survival (OS)
Overall Survival (OS)
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Secondary Outcomes
- Change from Baseline in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
- Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score
- Time to True Deterioration (TTD) in EORTC QLQ-C30 Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score
- Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score
- Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score
- Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
- Time to True Deterioration (TTD) in EORTC QLQ-C30 Physical Functioning (Items 1 to 5) Scale Combined Score
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Docetaxel
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+Lenvatinib vs. Lenvatinib Monotherapy
- Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
- Number of Participants Experiencing an Adverse Event (AE)
- Number of Participants Discontinuing Study Treatment Due to an Adverse Event (AE)
- 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
- Change from Baseline in EORTC Quality of Life Questionnaire Lung Cancer Module 13 (QLQ-LC13) Cough (Item 31) Scale Score
- Change from Baseline in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score
Investigators
Debra Kush
Scientific
Merck Sharp & Dohme LLC
Study Sites (38)
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