Study of Pembrolizumab, Lenvatinib and Chemotherapy Combination in First Line Extensive-stage Small Cell Lung Cancer

Lenvatinib is an oral, potent multiple receptor tyrosine kinase (RTK) i that selectively inhibits VEGF-driven VEGFR2 phosphorylation and suppressed proliferation and tube formation in human umbilical vein endothelial cell models. Antitumor activity of lenvatinib in vivo has been shown in numerous xenograft animals. These results suggest that lenvatinib may be a novel anticancer therapy through inhibition of angiogenesis and may be useful as either monotherapy or in combination with other anticancer drugs. Part 1 (safety run-in) and Part 2: The study intervention consists of: Dose: 8 mg (induction) and 20 mg (maintenance) Dose Frequency: Once daily Dose formulation: Capsule Route of administration: Oral Treatment duration: 4 cycles (induction) and no treatment duration limit (maintenance).

Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Part 1 (safety run-in) and Part 2: Dose: 200 mg Frequency: Day 1, Q3W Route: Intravenous Treatment Period: Up to 35 cycles or until reaching a discontinuation criterion

Standard first-line treatment for the vast majority of patients with SCLC, regardless of stage, involves combination chemotherapy with etoposide plus cisplatin or carboplatin. Pharmacotherapeutic group: Cytostatics, plant alkaloids and other natural products, derived from podophyllotoxin. Mechanism of action :The main effect of etoposide appears to be in the late S and early G2 phase of the cell cycle, in mammalian cells. Part 1 (safety run-in) and Part 2: Dose: 100 mg/m2 Frequency: Day 1-3, Q3W Route: Intravenous Treatment Period: 4 cycles

Pharmacotherapeutic group: Other antineoplastic agents, platinum compounds. Carboplatin, like cisplatin, binds to DNA to produce inter- and intra-strand cross-links cells exposed to carboplatin. DNA reactivity has been linked to cytotoxicity. Part 1 (safety run-in) and Part 2: Dose: AUC5 Frequency: Day 1, Q3W Route: Intravenous Treatment Period: 4 cycles