Sacituzumab Govitecan-hziy Receives FDA Breakthrough Therapy Designation for Extensive-Stage Small Cell Lung Cancer Treatment

Author(s):

Luke Halpern, Assistant Editor

Abstract data presented in September demonstrate that the drug elicited strong antitumor activity in the second line in both platinum-sensitive and -resistant patients.

The FDA granted breakthrough therapy designation to sacituzumab govitecan-hziy (Trodelvy; Gilead) for the treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease has continued progressing while being treated or following treatment with platinum-based chemotherapy, according to a news release from Gilead.¹

Small Cell Lung Cancer Cells: These small, round cells in the lungs divide rapidly and are known for early metastasis, resulting in highly aggressive cancer.

Treatments for extensive-stage small cell lung cancer are currently being developed. | Image Credit: © Best | stock.adobe.com

The regulatory action is based upon data from the ES-SCLC cohort global phase 2 TROPiCS-03 (NCT03964727) clinical trial, recently presented at the IASLC 2024 World Conference on Lung Cancer (WCLC) in September. Study results indicated that sacituzumab govitecan-hziy led to promising antitumor activity as a second-line treatment, with activity observed in patients with both platinum-sensitive and -resistant disease.^2,3

“For people 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,” the company said in the news release. “There is an urgent need for new and more effective approaches to care that can improve survival and slow the progression of the disease.”¹

According to the abstract presented at WCLC, overall response rate in the efficacy analysis was 41.9%, while clinical benefit rate (CBR) was 48.8%. Median duration of response was 4.73 months (95% CI, 3.52-6.70), while median progression-free survival (PFS) was 4.40 months (95% CI, 3.81-6.11). Median overall survival (OS) was 13.60 months (95% CI, 6.57-14.78), the investigators found, which is meaningful for patients in this disease cohort.³

Importantly, the safety analysis revealed that any-grade treatment-emergent, treatment-related adverse events (TE TRAEs) were observed in 97.7% of patients, with TE TRAEs of grade ≥3 found in 60.5% of patients. In a positive sign, there were no AEs that led to discontinuation of study treatment; however, one TE TRAE of neutropenic sepsis led to death in a patient.³

About The Trial

Trial Name: Study of Sacituzumab Govitecan in Participants With Metastatic Solid Tumors (TROPiCS-03)

ClinicalTrials.gov ID: NCT03964727

Sponsor: Gilead Sciences

Completion Date (Estimated): March 2023

This is the second breakthrough therapy designation to be granted for sacituzumab govitecan-hziy, which Gilead said is the first and only approved Trop-2-directed antibody-drug conjugate to demonstrate significant survival advantages in 2 types of metastatic breast cancer. Based on this preliminary evidence, the FDA felt sacituzumab govitecan-hziy could lead to meaningfully improved clinical outcomes compared with current standard of care.¹

Earlier this year, sacituzumab govitecan-hziy was issued a complete response letter by the FDA after results from the phase 3 EVOKE-01 trial did not meet its primary end point of OS in patients with metastatic non-small cell lung cancer. (NSCLC) Gilead said they are continuing to study sacituzumab govitecan-hziy in patients with NSCLC, ES-SCLC, and in certain cancer populations where Trop-2 is highly expressed.^1,4

Trop-2, a cell surface antigen, is expressed in multiple tumor types and in over 90% of lung and breast cancers. Sacituzumab govitecan-hziy has been purposely designed with a proprietary hydrolysable linker that is attached to topoisomerase I inhibitor payload SN-38.¹

“This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect,” Gilead said in the news release.¹

REFERENCES

1. Gilead. US FDA grants breakthrough therapy designation to Trodelvy (sacituzumab govitecan-hziy) for second-line treatment of extensive-stage small cell lung cancer. News Release. Released December 17, 2024. Accessed December 17, 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. Gilead. Gilead to present new Trodelvy data at the IASLC 2024 World Conference on Lung Cancer. News Release. Released September 5, 2024. Accessed December 17, 2024. https://www.gilead.com/news/news-details/2024/gilead-to-present-new-trodelvy-data-at-the-iaslc-2024-world-conference-on-lung-cancer

3. Dowlati A, Chiang AC, Cervantes A, et al. OA04.04 Sacituzumab govitecan as second-line treatment in patients with extensive stage small cell lung cancer. Journ Thoracic Onc. 2024;19(10):S16. doi:10.1016/j.jtho.2024.09.034

4. Ferruggia K. Phase 3 EVOKE-01 study in metastatic NSCLC falls short of primary end point. Pharmacy Times. Published February 20, 2024. Accessed Decembeer 17, 2024. https://www.pharmacytimes.com/view/phase-3-evoke-01-study-in-metastatic-nsclc-falls-short-of-primary-endpoint