A Randomized Phase III Study of Pembrolizumab Versus Pembrolizumab-Carboplatin-Pemetrexed for Locally Advanced or Metastatic Nonsquamous Non-small-cell Lung Cancer with PD-L1 50% or more (LAPLACE-50): Study Protocol

Pembrolizumab monotherapy or immune checkpoint inhibitor with platinum and pemetrexed combination chemotherapy are the standard therapies for patients with nonsquamous non-small-cell lung cancer (NSCLC) with programmed cell death ligand-1 (PD-L1) tumor proportion score (TPS) ≥ 50%. However, there are no data on the comparative effectiveness of the 2 regimens in patients with nonsquamous NSCLC with PD-L1 TPS ≥ 50%.This randomized, multicenter, phase III trial (LAPLACE-50, jRCTs031200078) was designed to compare the efficacy and safety of pembrolizumab with pembrolizumab-carboplatin-pemetrexed combination in patients with nonsquamous NSCLC with PD-L1 TPS ≥ 50%. Patients are eligible for enrollment if they are at least 20 years old; have pathologically confirmed locally advanced/metastatic nonsquamous NSCLC without sensitizing epidermal growth factor receptor or anaplastic lymphoma kinase mutations; have not received previous systemic therapy for metastatic disease; have an Eastern Cooperative Oncology Group performance status of 0 or 1; and have at least 1 measurable lesion. Patients will be excluded if they have symptomatic central nervous system metastases, interstitial pneumonitis, active autoimmune disease, or are on systemic immunosuppressive treatment. The patients will be randomized 1:1 to pembrolizumab (200 mg) or pembrolizumab (200 mg) plus carboplatin (area under the curve 5) plus pemetrexed (500 mg/m2) on day 1 of each 21-day treatment cycle. The primary endpoint is progression-free survival. The recruitment phase began in August 2020 and will enroll 290 patients.If the primary endpoint is achieved, pembrolizumab could be the first choice for first-line treatment in patients with nonsquamous NSCLC with PD-L1 TPS ≥ 50%.