Week 4, May 2024: Extensive-Stage Small-Cell Lung Cancer
Biointron2024-05-28Read time: 2 mins
ADCs for ES-SCLC. Image credit: DOI: 10.3390/genes15060701
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.
This report aims to explore the events and trends of the biopharmaceutical industry in Q2 (April, May, June). Besides crovalimab and Vyloy, two more novel antibody drugs have been approved this year
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Anti-drug antibodies (ADAs) are immune system proteins that can develop in response to therapeutic drugs, particularly biologics like monoclonal antibodies. These biopharmaceuticals have significantly advanced therapies for cancer and autoimmune diseases, but their long-term use can elicit immunogenicity due to repeated administration. The host immune system may recognize epitopes in the biologic drug as foreign, triggering the production of ADAs. This can lead to the formation of drug–ADA immune complexes, which accelerate drug clearance and potentially neutralize the drug's efficacy.
