FDA grants to expedite review of zotatifin plus Faslodex (fulvestrant) and Verzenio (abemaciclib) for patients with ER–positive, HER2-negative advanced or metastatic breast cancer.
The FDA has granted Fast Track Designation to eFFECTOR Therapeutics, Inc’s zotatifin (eFT226) plus Faslodex (fulvestrant) and Verzenio (abemaciclib) as a second- or third-line treatment for patients with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer whose disease progressed after treatment with endocrine therapy and a CDK4/6 inhibitor.1
The FDA granted the designation based on data from preclinical and clinical trials of zotatifin, as well as safety and efficacy data with the combination.1
"We’re grateful to receive this fast track designation from [the] FDA, which is a meaningful milestone for the development of zotatifin and reflects the demonstrated potential for zotatifin in combination with fulvestrant and abemaciclib to address unmet needs in ER-positive/HER2-negative breast cancer,” said Steve Worland, PhD, eFFECTOR chief executive officer, in a press release.1 “We value the opportunities provided by fast track designation for frequent interactions with the FDA review team as we advance this development program for zotatifin and look forward to providing further data updates and development plans at the 2023 San Antonio Breast Cancer Symposium.”
The FDA awards Fast Track designation to medications either alone or in combination with one or more other therapies that demonstrate the potential to address unmet medical needs for patients with serious or life-threatening diseases or conditions. Fast Track designation is intended to expedite the review of medications for serious and life-threatening conditions to allow approved products to reach the market quickly.
Zotatifin is a sequence-selective small molecule inhibitor of the RNA helicase eIF4A. The drug is designed to inhibit the expression of a cancer-driving protein network, which includes Cyclins D and E, CDKs 2, 4 and 6, select RTKs, and KRAS. An ongoing phase 1/2 dose-escalation and dose-expansion study (NCT04092673) is currently evaluating zotatifin for the treatment of patients with ER-positive/HER2-negative metastatic breast cancer.
According to data presented at the 2023 American Society of Clinical Oncology meeting, among patients previously administered a median of four lines of therapy for metastatic disease, five of 19 (26%) RECIST-evaluable patients achieved a partial response (PR), with four confirmed and one unconfirmed. The five patients achieving a PR previously experienced disease progression during treatment with CDK 4/6 and fulvestrant.2
Dose escalation was resumed for the combination of zotatifin with fulvestrant based on safety and tolerability data. Additional updates regarding interim data from the triplet cohort and the resumed dose escalation cohorts will be presented at the San Antonio Breast Cancer Conference on December 8, 2023.
1. eFFECTOR receives U.S. FDA fast track designation for zotatifin in combination with fulvestrant and abemaciclib for treatment of ER+/HER2- advanced metastatic breast cancer. News release. eFFECTOR Therapeutics. November 28, 2023. Accessed November 30, 2023. https://www.globenewswire.com/news-release/2023/11/28/2786889/0/en/eFFECTOR-Receives-U-S-FDA-Fast-Track-Designation-for-Zotatifin-in-Combination-with-Fulvestrant-and-Abemaciclib-for-Treatment-of-ER-HER2-Advanced-Metastatic-Breast-Cancer.html
2. Rosen E, Sharma M, Berz D, et al. Phase 1/2 dose expansion study evaluating first-in-class eIF4A inhibitor zotatifin in patients with ER+ metastatic breast cancer. J Clin Oncol. 2023;41(suppl 16):1080. doi:10.1200/JCO.2023.41.16_suppl.1080