Antibody-Based Therapeutics in Small Cell Lung Cancer: A Narrative Review
Novel antibody‑based agents could potentially acquire a prominent role in the treatment of SCLC.
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 tumours, including SCLC. T‑cell engagers are molecules able to trigger the T‑cell‑mediated tumour cell death binding, at the same time, a T‑cell and a tumour 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 tumour‑directed monoclonal antibody conjugated to a cytotoxic payload able to selectively kill tumour 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 tumour 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.
SCLC remains a highly lethal disease with limited treatment options; effective antibody‑based therapies may improve outcomes by providing new mechanisms of tumour cell killing and circumventing resistance to conventional chemotherapy and immunotherapy.
Evidence level: Korai humán adat. Kis vagy feltáró emberi adat.
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