A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous Zotatifin (eFT226) in Subjects With Selected Advanced Solid Tumor Malignancies
Effector Therapeutics
Summary
This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of Zotatifin (eFT226) in subjects with selected advanced solid tumor malignancies.
Description
Part 1 (Dose Escalation): Completed; Recommended Phase 2 Dose (RP2D) and Maximum Tolerated Dose (MTD) identified Part 1a (Dose Escalation) This cohort will enroll patients with an advanced breast cancer that is refractory or intolerant to SOC therapy. Part 1b (Dose Escalation) This cohort will enroll patients with an advanced breast cancer that is refractory or intolerant to SOC therapy. Part 2 (Expansion Cohort) provides defined expansion cohorts to further explore the safety, pharmacology, and clinical activity of eFT226 monotherapy and in various combinations in subjects with previously…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Key Criteria: Parts 1a and 1b (Dose Escalation + Fulvestrant): * Patient has histological or cytological confirmation of breast cancer. * Patient has metastatic disease or locoregionally recurrent disease which is refractory or intolerant to existing therapy(ies) known to provide clinical benefit. * Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows: * Minimum of one prior line of therapy for advanced/metastatic disease. * Maximum of five prior lines of therapy for advanced/metastatic disease. * Recurrence or progression on at least one line of endocrin…
Interventions
- DrugeFT226
eFT226 is a novel small-molecule, investigational drug being developed by eFFECTOR Therapeutics as an anticancer therapy. eFT226 is a potent and selective inhibitor of eIF4A1-mediated translation and selectively regulates the translation of a subset of mRNAs based on sequence specific recognition motifs in their 5'-UTR. eIF4A1 inhibition by eFT226 downregulates expression of receptor tyrosine kinases and KRAS, leading to decreased signaling through the PI3K/AKT and MAPK pathways. Preclinical efficacy testing of eFT226 demonstrates activity across models of solid tumor cancers with amplifications in HER2, FGFR1/2 and mutations in KRAS (including breast, NSCLC and CRC).
- DrugSotorasib
Recommended dosage: 960 mg orally once daily
- DrugFulvestrant
500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter
- DrugAbemaciclib
Dose in combination with fulvestrant: 150 mg twice daily
- DrugTrastuzumab
600 mg every 3 weeks
Locations (14)
- University of Southern CaliforniaLos Angeles, California
- Valkyrie Clinical TrialsLos Angeles, California
- Hoag Memorial Hospital PresbyterianNewport Beach, California
- Stanford UniversityPalo Alto, California
- START MidwestGrand Rapids, Michigan
- Comprehensive Cancer Centers of NevadaLas Vegas, Nevada