Week 4, May 2024: Extensive-Stage Small-Cell Lung Cancer

Extensive-stage small-cell lung cancer (ES-SCLC) is a particularly aggressive form of lung cancer characterized by rapid growth and early metastasis. Antibody drugs, especially immune checkpoint inhibitors, have emerged as a promising treatment option for ES-SCLC. These drugs work by targeting specific proteins on cancer cells or immune cells, such as PD-L1, to enhance the body's immune response against the tumor.

This week, Amgen made headlines as the FDA approved their novel drug Imdelltra (tarlatamab-dlle), a novel bispecific T-cell engager, for ES-SCLC. The approval could lead the drug to blockbuster status for the company’s cancer portfolio. Tarlatamab works by binding to both DLL3 on tumor cells and CD3 on T cells, thus activating T cells to kill DLL3-expressing SCLC cells. This leads to the formation of a cytolytic synapse with lysis of the cancer cell. The DLL3 protein is expressed on the surface of SCLC cells in about 85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it a potential target.

Meanwhile, a recent review by researchers at the IEO Istituto Europeo di Oncologia highlighted the evolving scenario of ES-SCLC immunotherapy, with high expectations from bispecific antibodies like QL1706 (an anti-PD-1/anti-CTLA4 tested in a Phase II trials) and Cadonilimab (AK104) (another anti-PD-1/anti-CTLA4 for combination therapy). Antibody-drug conjugates (ADCs) like Rova-T (rovalpituzumab tesirine), Trodelvy (sacituzumab govitecan), ABBV-011 (SEZ6-targeted, calicheamicin-based) and others have also shown promise.

Atezolizumab and durvalumab are two antibody drugs that have been previously approved for use in combination with chemotherapy for ES-SCLC. Clinical trials have shown that adding these immune checkpoint inhibitors to standard chemotherapy regimens can improve overall survival and progression-free survival in patients with ES-SCLC. These advancements represent a significant step forward in the management of a disease that has traditionally had very limited treatment options and poor prognosis.