FDA Fast Tracks eFFECTOR Therapeutics' Zotatifin Combo for ER+/HER2– Breast Cancer
FDA to expedite review of zotatifin plus Faslodex (fulvestrant) and Verzenio (abemaciclib) as a second- or third-line treatment for patients with estrogen receptor–positive, human epidermal growth factor receptor 2-negative advanced or metastatic breast cancer whose disease progressed after treatment with endocrine therapy and a CDK4/6 inhibitor.
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
Image credit: SciePro | stock.adobe.com
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.
References
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
FDA Grants Priority Review to Regeneron’s Eylea for Macular Edema Following Retinal Vein Occlusion
April 18th 2025Regulatory action was based on data from the Phase III QUASAR trial, which demonstrated that Eylea HD dosed every eight weeks achieved non-inferior visual acuity outcomes compared to Eylea in patients with macular edema following retinal vein occlusion.
Addressing Disparities in Psoriasis Trials: Takeda's Strategies for Inclusivity in Clinical Research
April 14th 2025LaShell Robinson, Head of Global Feasibility and Trial Equity at Takeda, speaks about the company's strategies to engage patients in underrepresented populations in its phase III psoriasis trials.
New Insights Into T Cell Exhaustion and Inflammation in Long COVID
April 17th 2025Nigel McCracken, chief operating officer, Virax Biolabs, discusses new findings that reveal altered cytokine activity and evidence of T cell exhaustion in long COVID patients, providing deeper insight into post-infection immune disruption.
Key Findings of the NIAGARA and HIMALAYA Trials
November 8th 2024In this episode of the Pharmaceutical Executive podcast, Shubh Goel, head of immuno-oncology, gastrointestinal tumors, US oncology business unit, AstraZeneca, discusses the findings of the NIAGARA trial in bladder cancer and the significance of the five-year overall survival data from the HIMALAYA trial, particularly the long-term efficacy of the STRIDE regimen for unresectable liver cancer.
Amgen’s Imdelltra Demonstrates Significant Overall Survival Improvement in Small Cell Lung Cancer
April 16th 2025In the Phase III DeLLphi-304 trial, patients with small cell lung cancer administered Imdelltra achieved a statistically significant and clinically meaningful improvement in overall survival compared to standard-of-care chemotherapy.
