Gilead's Trodelvy Falls Short of Phase III Trial Primary Endpoint of Improved Overall Survival in NSCLC

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Data from the Phase III EVOKE-01 trial (NCT05089734) show that Gilead Sciences, Inc’s Trodelvy (sacituzumab govitecan-hziy) did not achieve the primary endpoint of overall survival (OS) in patients with previously treated, metastatic non-small cell lung cancer (NSCLC).¹

EVOKE-01 was comparing Trodelvy with docetaxel for the treatment of patients with metastatic or advanced NSCLC who progressed on or following platinum-based chemotherapy and checkpoint inhibitor therapy.

“The totality of our data gives us continued confidence in Trodelvy’s potential in metastatic NSCLC, and in our broader lung cancer clinical development program,” said Gilead Sciences Chief Medical Officer Merdad Parsey, MD, PhD, in a press release. “Treating metastatic NSCLC that has progressed on or after platinum-based chemotherapy presents significant challenges and the need for safe and effective treatments remains urgent. We will work to further identify the metastatic NSCLC patient populations that may benefit from Trodelvy.”¹

Trodelvy is a conjugated Trop-2-directed antibody and topoisomerase inhibitor previously approved for the treatment of patients with triple-negative breast cancer administered two prior therapies at minimum for metastatic disease; for certain patients with pre-treated HR+/HER2- metastatic breast cancer; and for patients with locally advanced or metastatic urothelial cancer previously administered a platinum-containing chemotherapy and either PD-1 or PD-L1 inhibitor. The drug is included in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, including a category 1 recommendation for use in adults with second-line metastatic triple-negative breast cancer, defined as at least two prior therapies with at least one line for metastatic disease.²

The global, multi-center, open-label, EVOKE-01 trial randomly assigned 603 patients 1:1 with advanced or metastatic NSCLC who progressed on or following platinum-based chemotherapy and checkpoint inhibitor therapy. In addition to the primary endpoint of OS, secondary endpoints of the trial included progression-free survival, objective response rate, duration of response, and disease control rate as assessed by investigator per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and safety.

Results from the trial show a numerical OS improvement for Trodelvy, including among patients with both squamous and non-squamous histology. Investigators found a more than three-month difference in median OS in favor of Trodelvy among a sub-group of patients who did not respond to previous treatment with an anti-PD-L1 therapy, which was more than 60% of patients enrolled in the trial; however, the magnitude of this difference was not observed among patients who did achieve a response to last prior anti PD-L1 therapy, according to Gilead. Although the analysis was pre-specified in the protocol, it was not alpha-controlled for statistical testing, Gilead stated in a press release.

Gilead said it will continue research efforts to further evaluate the role Trodelvy may play in the treatment of patients with metastatic NSCLC because of the high unmet need in this population. The company added that it discuss these trial data with regulators and present the findings at an upcoming medical meeting.

The ongoing Phase III EVOKE-03 study is currently enrolling patients based on positive preliminary efficacy and safety data from the Phase II EVOKE-02 study of Trodelvy plus pembrolizumab (Keytruda) in patients with metastatic PD-L1 high NSCLC.

References

1. Gilead Provides Update on Phase 3 EVOKE-01 Study. Gilead Sciences Inc. News release. January 22, 2024. Accessed January 23, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/1/gilead-provides-update-on-phase-3-evoke-01-study

2. U.S. FDA Approves Trodelvy® in Pre-treated HR+/HER2- Metastatic Breast Cancer. Gilead. News release. February 3, 2023. Accessed January 23, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2023/2/us-fda-approves-trodelvy-in-pretreated-hrher2-metastatic-breast-cancer.