Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies
- Conditions
- Solid Tumor, Adult
- Interventions
- Registration Number
- NCT04092673
- Lead Sponsor
- Effector Therapeutics
- Brief 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.
- Detailed 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 treated advanced solid tumor malignancies.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2: Cohort Expansion, Combination, NSCLC, Sotorasib (ECNS) Sotorasib Cohort ECNS; Combination therapy partner administered per SOC at the approved dose. Part 1: Sequential escalation (Completed) eFT226 eFT226 administered IV weekly in 21-day cycles; dose escalated in sequential cohorts after subjects enrolled in a given cohort have completed DLT evaluation period. Part 2: Cohort Expansion, Monotherapy, NSCLC, KRAS (EMNK) eFT226 Cohort EMNK Part 2: Cohort Expansion, Monotherapy, Breast, FGFR (EMBF) eFT226 Cohort EMBF Part 2: Cohort Expansion, Monotherapy, Breast, HER2 (EMBH) eFT226 Cohort EMBH Part 2: Cohort Expansion, Combination, Breast, Fulvestrant (ECBF) Fulvestrant Cohort ECBF; Combination therapy partner administered per SOC at the approved dose. Part 2: Cohort Expansion, Combination, Breast, Fulvestrant+Abemaciclib (ECBF+A) Fulvestrant Cohort ECBF+A; Combination therapy partner administered per SOC at the approved dose. Part 2: Cohort Expansion, Combination, Breast, Fulvestrant+Abemaciclib (ECBF+A) Abemaciclib Cohort ECBF+A; Combination therapy partner administered per SOC at the approved dose. Part 2: Cohort Expansion, Combination, Breast, Trastuzumab (ECBT) Trastuzumab Cohort ECBT; Combination therapy partner administered per SOC at the approved dose. Part 1a: Dose Escalation, Combination, Breast Fulvestrant eFT226 administered IV weekly in 21-day cycles. Fulvestrant will also be given. Dose escalations per protocol. Part 1b Dose Escalation, Combination, Breast Fulvestrant eFT226 administered IV every other week in 14-day cycles. Fulvestrant will also be given. Dose escalations per protocol. Part 2 Cohort Expansion, Combination, Breast, Fulvestrant, Cyclin D1 Fulvestrant ECBF-D1; Combination therapy partner administered per SOC at the approved dose.
- Primary Outcome Measures
Name Time Method Part 2: (Combination Cohorts) Determine MTD Through study completion, approximately 12 months determined by occurrence of first cycle Dose Limiting Toxicities (DLTs) within the study design
Part 2: Percent change in tumor dimensions of target lesions- Efficacy Through study completion, approximately 12 months calculated by the percentage change from baseline in the sum of the LD of target lesions
Parts 1a and 1b; incidence of AEs, serious adverse events (SAEs), and DLTs Through study completion, approximately 12 months according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)
Parts 1a and 1b: MTD Through study completion, approximately 12 months determined by occurrence of first cycle DLTs within a 3+3 or 3+3+3 clinical trial design
Parts 1a and 1b: RP2D Through study completion, approximately 12 months determine by Incidence, type, and severity of AEs and SAEs graded as per NCI CTCAE
Part 2: Objective Response Rate- Efficacy Through study completion, approximately 12 months defined as confirmed Complete Response (CR) or Partial Response (PR)
Part 2: (Combination Cohorts) Incidence, type, and severity of AEs and SAEs Through study completion, approximately 12 months via adverse event monitoring
Part 2: (Combination Cohorts) Determine RP2D Through study completion, approximately 12 months determined by incidence and type of DLTs, and incidence, type, and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Part 2: Time to Response (TTR)- Efficacy Through study completion, approximately 12 months defined as the interval from the start of study therapy to the first documentation of an objective response
Part 2: Duration of Response (DOR)- Efficacy Through study completion, approximately 12 months defined as the interval from the first documentation of objective response to the earlier of the first documentation of disease progression or death from any cause
- Secondary Outcome Measures
Name Time Method Parts 1a and 1b: Objective response Through study completion, approximately 12 months determined by confirmed CR or PR
Part 2: (Monotherapy and Combination Cohorts) Incidence and severity of AEs, SAEs, and additional safety parameters Through study completion, approximately 12 months via adverse event monitoring
Parts 1a and 1b: Percent change in tumor dimensions of target lesions Through study completion, approximately 12 months calculated by the percentage change from baseline in the sum of the LD of target lesions
Parts 1a and 1b: DOR Through study completion, approximately 12 months defined as the interval from the first documentation of objective response to the earlier of the first documentation of disease progression or death from any cause
Parts 1a and 1b: PFS Through study completion, approximately 12 months defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression or death from any cause
Evaluate plasma Pharmacokinetic (PK) parameters of eFT226including terminal state volume of distribution Through study completion, approximately 12 months including terminal state volume of distribution
Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 including terminal phase rate constant Through study completion, approximately 12 months including terminal phase rate constant
Parts 1a and 1b: TTR Through study completion, approximately 12 months defined as the interval from the start of study therapy to the first documentation of an objective response
Part 2: Progression Free Survival Through study completion, approximately 12 months defined as the interval from the start of study therapy to the earlier of the first documentation of disease progression or death from any cause
Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 Through study completion, approximately 12 months including total body clearance
Trial Locations
- Locations (14)
Memorial Sloan Kettering Cancer Center- Westchester
šŗšøHarrison, New York, United States
Stanford University
šŗšøPalo Alto, California, United States
START Midwest
šŗšøGrand Rapids, Michigan, United States
Memorial Sloan Kettering Cancer Center- David H. Koch Center for Cancer Care
šŗšøNew York, New York, United States
Memorial Sloan Kettering Cancer Center- Monmouth
šŗšøMiddletown, New Jersey, United States
Memorial Sloan Kettering Cancer Center- Commack
šŗšøCommack, New York, United States
University of Toledo Medical Center
šŗšøToledo, Ohio, United States
Valkyrie Clinical Trials
šŗšøLos Angeles, California, United States
University of Southern California
šŗšøLos Angeles, California, United States
Hoag Memorial Hospital Presbyterian
šŗšøNewport Beach, California, United States
MD Anderson Cancer Center
šŗšøHouston, Texas, United States
New Experimental Therapeutics of San Antonio - NEXT Oncology
šŗšøSan Antonio, Texas, United States
Virginia Cancer Specialists
šŗšøFairfax, Virginia, United States
Comprehensive Cancer Centers of Nevada
šŗšøLas Vegas, Nevada, United States