FDA Grants Breakthrough Therapy Designation to Gilead’s Trodelvy for Extensive-Stage Small Cell Lung Cancer

Image Credit: Adobe Stock Images/Andres Mejia

The FDA has granted Breakthrough Therapy Designation (BTD) to Gilead Sciences’ Trodelvy (sacituzumab govitecan-hziy) for adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has progressed following platinum-based chemotherapy. The BTD was based on promising results from the global Phase II TROPiCS-03 study. Trodelvy is the only approved Trop-2-directed antibody-drug conjugate that has demonstrated meaningful survival advantages in two different types of metastatic breast cancers, according to Gilead.1

Data from TROPiCS-03 were recently presented at the IASLC 2024 World Conference on Lung Cancer in September. The trial consisted of adult patients with ES-SCLC that progressed after no more than one prior line of platinum-based chemotherapy and anti-PD-L1 therapy. All patients received 10 mg/kg on days one and eight of a 21-day cycle. The primary endpoint of the study was overall response rate (ORR) by investigator assessment per RECIST v1.1, while secondary endpoints included clinical benefit rate (CBR), duration of response (DOR), progression-free survival, overall survival, and safety.^2,3

At the time of data cutoff on March 8, 2024, the investigator-assessed ORR with Trodelvy was 41.9%. Further, disease stability and progressive disease were observed in 41.9% and 9.3% of patients, respectively; whereas 7% of patients were not assessed. Additional results found that the disease control rate was 83.7%, the CBR was 48.8%, the median DOR rate was 4.7 months— with 48.2% of responders maintaining a response at six months—and the median time to response was 1.4 months.⁴

According to Gilead, ES-SCLC accounts for 70% of all SCLC cases and is a highly aggressive cancer with limited treatment options, particularly for patients who fail first-line therapies. SCLC accounts for 15% of all lung cancers. For patients with ES-SCLC whose disease does not respond to current first-line standard of care, the prognosis is often poor, and treatment options are limited.¹

According to the American Cancer Society, lung cancer is the leading cause of cancer-related mortality in the United States, accounting for one in every five cancer deaths. Annually, more people due from lung cancer than from colon, breast, and prostate cancers combined. It is also estimated that by the end of the year, there will be 234,580 new cases of lung cancer and 125,070 deaths. While it mainly occurs in older people, a very small number of people under 45 years of age have been diagnosed. The average age of diagnosis is 70 years.

Cases of lung cancer have been decreasing, in part due to the fact that more people are quitting smoking or haven’t started. The number of deaths from lung cancer continues to drop as well, due to fewer people smoking and advances in early detection and treatment. Currently, the chance that a male will develop lung cancer in his lifetime is about 1 in 16, whereas for a woman, the risk is about 1 in 17.⁵

Currently, Trodelvy has been approved in over 50 countries for second-line or later metastatic triple-negative breast cancer patients (TNBC) and in more than 40 countries for certain patients with pre-treated HR-positive/HER2-negative metastatic breast cancer. In addition to the aforementioned indications, Trodelvy is being investigated for use in other TNBC and HR-positive/HER2-negative breast cancer populations, as well as a range of tumor types in which Trop-2 is highly expressed, including small cell lung cancer and first-line metastatic non-small cell lung cancer where Trodelvy has shown clinical activity through the TROPiCS-03 proof-of-concept study and the EVOKE-02 proof-of-concept study, respectively.¹

References

1. U.S. FDA Grants Breakthrough Therapy Designation to Trodelvy® (sacituzumab govitecan-hziy) for Second-Line Treatment of Extensive-Stage Small Cell Lung Cancer. Gilead. December 17, 2024. Accessed December 18, 2024. https://www.gilead.com/news/news-details/2024/us-fda-grants-breakthrough-therapy-designation-to-trodelvy-sacituzumab-govitecan-hziy-for-second-line-treatment-of-extensive-stage-small-cell-lung-cancer

2. Sacituzumab Govitecan-hziy Receives FDA Breakthrough Therapy Designation for Extensive-Stage Small Cell Lung Cancer Treatment. Pharmacy Times. December 17, 2024. Accessed December 18, 2024. https://www.pharmacytimes.com/view/sacituzumab-govitecan-hziy-receives-fda-breakthrough-therapy-designation-for-extensive-stage-small-cell-lung-cancer-treatment

3. OA04.04 Sacituzumab Govitecan as Second-Line Treatment in Patients with Extensive Stage Small Cell Lung Cancer. ScienceDirect. Accessed December 18, 2024. https://www.sciencedirect.com/science/article/abs/pii/S1556086424009080

4. FDA Grants Breakthrough Therapy Designation to Sacituzumab Govitecan for Second-Line ES-SCLC. OncLive. December 17, 2024. Accessed December 18, 2024. https://www.onclive.com/view/fda-grants-breakthrough-therapy-designation-to-sacituzumab-govitecan-for-second-line-es-sclc

5. Key Statistics for Lung Cancer. American Cancer Society. Accessed December 18, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html