Abstract
Small-cell lung cancer (SCLC) is the most aggressive lung cancer, mostly diagnosed at advanced stage, and with few therapeutic options for patients failing the first-line treatment. Antibody-based therapies, such as antibody-drug conjugates and T-cell engagers, are emerging as a promising option in the treatment of various solid tumors, including SCLC. T-cell engagers are molecules able to trigger the T-cell-mediated tumor cell death binding, at the same time, a T-cell and a tumor cell target. Tarlatamab is a DLL3-directed bi-specific T-cell engager (BiTE) whose efficacy was evaluated in a Phase 2 study. Antibody-drug conjugates (ADC) consist of a tumor-directed monoclonal antibody conjugated to a cytotoxic payload able to selectively kill tumor cells through different mechanisms. Ifinatamab-deruxtecan is an anti-B7-H3 ADC showing efficacy in pretreated SCLC patients in a phase 2 clinical trial. Sacituzumab govitecan is a Trop-2-directed ADC already used in other tumor types and evaluated in SCLC in the phase 2 TROPiCS-03 trial, with positive results. Bispecific antibodies targeting VEGF and PD-(L)1 showed antitumor activity in phase 1 and 2 clinical trials. Other antibody-based agents are currently at an earlier phase of their clinical development and showed a promising activity. Novel antibody-based agents could potentially acquire a prominent role in the treatment of SCLC, a field with few therapeutic options. Direct comparisons with the current standard of care still lack, however Phase 3 trials are currently ongoing.