FDA Designates Trodelvy as Breakthrough Therapy for Second-Line Small Cell Lung Cancer Treatment

Gilead Sciences, Inc., headquartered in Foster City, California, has announced that the U.S. Food and Drug Administration (FDA) has awarded Breakthrough Therapy Designation to Trodelvy® (sacituzumab govitecan-hziy). This designation is for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) that has progressed following treatment with platinum-based chemotherapy.

The decision by the FDA is grounded in findings from the Phase 2 TROPiCS-03 study's ES-SCLC cohort, which indicated that Trodelvy shows promising results as a second-line therapy for this type of cancer. Results shared at the IASLC 2024 World Conference on Lung Cancer revealed that Trodelvy displayed significant antitumor activity in cases resistant to platinum treatments, as well as in those that were sensitive to it. The safety profile noted in the study was consistent with past research on Trodelvy. Encouraged by these findings, Gilead plans to commence a Phase 3 clinical trial to explore further its efficacy in treating ES-SCLC.

Lung cancer ranks as the second most common cancer diagnosis in the United States and is the leading cause of cancer-related deaths. Small cell lung cancer (SCLC) constitutes roughly 15% of all lung cancer cases, with about 70% of SCLC patients diagnosed at an extensive stage. This stage is characterized by cancer spreading to both lungs, lymph nodes, or other organs. Current treatment options for ES-SCLC are limited, especially when the disease does not respond to initial treatments like platinum-based chemotherapy or immunotherapy, resulting in a generally poor prognosis. Thus, there is an urgent need for new and more effective treatment options to improve patient survival rates and halt the disease's progression.

The Breakthrough Therapy Designation is a mechanism to accelerate the development and review of drugs intended for serious or life-threatening conditions, especially when preliminary evidence suggests a substantial improvement over existing treatments. This marks the second time Trodelvy has received such a designation.

Trodelvy is distinguished as the first approved Trop-2-directed antibody-drug conjugate (ADC) to show significant survival benefits in two forms of metastatic breast cancer. Currently, Trodelvy is being evaluated in Phase 3 trials both as a standalone treatment and in combination with other agents across various tumor types. These studies are part of collaborative efforts with academic and industry partners, as well as the global cancer research community.

Trodelvy, a pioneering Trop-2-targeting ADC, was developed to exploit Trop-2, a cell surface antigen prevalent in over 90% of breast and lung cancers. The drug is crafted with a proprietary linker that attaches to SN-38, a topoisomerase I inhibitor, facilitating powerful effects on Trop-2 expressing cells and the surrounding tumor environment.

Trodelvy is already approved in over 50 countries for treating metastatic triple-negative breast cancer (TNBC) and in over 40 countries for specific types of pre-treated HR+/HER2- metastatic breast cancer. The drug is being studied for broader applications, including other breast cancer populations and various tumor types with high Trop-2 expression, such as small cell lung cancer and metastatic non-small cell lung cancer. Furthermore, Trodelvy is under investigation for potential use in treating head and neck cancer, as well as gynecological cancers.

In the United States, Trodelvy is indicated for adults with unresectable locally advanced or metastatic TNBC who have tried at least two prior systemic therapies, and for those with HR-positive, HER2-negative breast cancer who have undergone endocrine-based therapy alongside two additional systemic treatments. Despite its benefits, Trodelvy comes with a boxed warning for severe neutropenia and diarrhea. Patients require careful monitoring, and interventions are recommended for managing these adverse effects. Other potential risks include hypersensitivity reactions, nausea, and vomiting, emphasizing the need for proper patient management and premedication strategies.