Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04092673|
Recruitment Status : Not yet recruiting
First Posted : September 17, 2019
Last Update Posted : September 17, 2019
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumor, Adult||Drug: eFT226||Phase 1 Phase 2|
Part 1 (dose escalation) will enroll subjects with an advanced solid tumor that is refractory or intolerant to standard of care therapy, where the tumor is pancreatic adenocarcinoma (no molecular typing) or any other solid tumor that has a documented activating mutation, amplification, or fusion of HER2, ERBB3, FGFR1, FGFR2, or an activating mutation in KRAS.
Subjects will be assigned sequentially to increasing eFT226 doses. The starting dose of eFT226 is 0.005 mg/kg administered IV weekly in 21 day cycles. eFT226 doses will be escalated in subsequent cohorts after subjects enrolled in a given cohort have completed the 21-day dose-limiting toxicity (DLT) evaluation period. Dose escalation in Part 1 will enroll subjects based on 3+3 design, whereby 3 subjects will be initially enrolled and treated at each dose level.
To obtain as robust a data set as possible regarding PK, safety and tolerability in a diverse population prior to selecting the RP2D, the MTD and MTD-1 cohorts may be backfilled up to 15 subjects total in each cohort.
Part 2 (Expansion Cohort) of the study will provide cohort expansion to further explore the safety, pharmacology, and clinical activity of eFT226 monotherapy in subjects with previously treated advanced solid tumor malignancies. Part 2 will be based on results observed in Part 1 and will be defined by amendment to the protocol.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||dose escalation, 3+3 design|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies|
|Estimated Study Start Date :||September 2019|
|Estimated Primary Completion Date :||April 2021|
|Estimated Study Completion Date :||December 2021|
Experimental: sequential escalation
eFT226 is administered IV weekly in 21 day cycles. eFT226 doses will be escalated in sequential cohorts after subjects enrolled in a given cohort have completed the 21-day dose-limiting toxicity (DLT) evaluation period. Starting dose is 0.005mg/kg/week, potentially escalating to 0.12mg/kg/week until MTD and RP2D are established
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).
Other Name: selective translation inhibitor
- Incidence of Treatment-emergent adverse events (safety and tolerability) [ Time Frame: Through study completion, on average 12 months ]via adverse event monitoring
- Incidence of serious adverse events (safety and tolerability) [ Time Frame: Through study completion, on average 12 months ]via adverse event monitoring
- Establish Maximum Tolerated Dose (MTD) as determined by occurrence of first cycle Dose Limiting Toxicity (DLT) [ Time Frame: Through study completion, on average 12 months ]determine MTD by occurrance of DLTs within a 3+3 design or recommended
- Establish Recommended Phase 2 Dose (RP2D) [ Time Frame: Through study completion, on average 12 months ]Determined by incidence, type, and severity of DLTs, AEs, and SAEs
- evaluate plasma PK parameters of eFT226 - maximum concentration (Cmax) [ Time Frame: Through study completion, on average 12 months ]Plasma for evaluation of Cmax to be collected at multiple time points
- evaluate plasma PK parameters of eFT226 - Area under the plasma concentration -time curve (AUC) [ Time Frame: Through study completion, on average 12 months ]Plasma for evaluation of AUC to be collected at multiple time points
- evaluate plasma PK parameters of eFT226 - terminal phase half-life (t1/2) [ Time Frame: Through study completion, on average 12 months ]Plasma for evaluation of t1/2 to be collected at multiple time points
- antitumor activity and survival [ Time Frame: From start of study therapy to the first documentation of disease progression or death from any cause, which ever came first, assessed up to 100 months ]determination of response and progression will be evaluated using RECIST 1.1
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04092673
|Contact: Lyon Gleich, MD||1-513-579-9911 ext 12400||L.Gleich@Medpace.com|
|United States, Ohio|
|University of Toledo||Not yet recruiting|
|Toledo, Ohio, United States, 43606|
|Contact: John Nemunaitis, MD|
|United States, Texas|
|MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|NEXT Oncology||Not yet recruiting|
|San Antonio, Texas, United States, 78229|
|Contact: Raghad Karim, MD 210-580-9500|
|Study Director:||Lyon Gleich, MD||Medpace, Inc.|