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Trial record 1 of 3 for:    eft226
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Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies (Zotatifin)

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 : Recruiting
First Posted : September 17, 2019
Last Update Posted : November 18, 2022
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Solid Tumor, Adult Drug: eFT226 Drug: Sotorasib Drug: Fulvestrant Drug: Abemaciclib Drug: Trastuzumab Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 228 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose Escalation, 3+3, 3+3+3
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous Zotatifin (eFT226) in Subjects With Selected Advanced Solid Tumor Malignancies
Actual Study Start Date : October 25, 2019
Estimated Primary Completion Date : July 31, 2023
Estimated Study Completion Date : September 30, 2023

Arm Intervention/treatment
Experimental: Part 1: Sequential escalation (Completed)
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.
Drug: eFT226
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

Experimental: Part 2: Cohort Expansion, Monotherapy, NSCLC, KRAS (EMNK)
Cohort EMNK
Drug: eFT226
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

Experimental: Part 2: Cohort Expansion, Monotherapy, Breast, FGFR (EMBF)
Cohort EMBF
Drug: eFT226
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

Experimental: Part 2: Cohort Expansion, Monotherapy, Breast, HER2 (EMBH)
Cohort EMBH
Drug: eFT226
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

Experimental: Part 2: Cohort Expansion, Combination, Breast, Fulvestrant (ECBF)
Cohort ECBF; Combination therapy partner administered per SOC at the approved dose.
Drug: Fulvestrant
500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter
Other Name: Faslodex

Experimental: Part 2: Cohort Expansion, Combination, NSCLC, Sotorasib (ECNS)
Cohort ECNS; Combination therapy partner administered per SOC at the approved dose.
Drug: Sotorasib
Recommended dosage: 960 mg orally once daily
Other Name: Lumarkus

Experimental: Part 2: Cohort Expansion, Combination, Breast, Fulvestrant+Abemaciclib (ECBF+A)
Cohort ECBF+A; Combination therapy partner administered per SOC at the approved dose.
Drug: Fulvestrant
500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter
Other Name: Faslodex

Drug: Abemaciclib
Dose in combination with fulvestrant: 150 mg twice daily
Other Name: Verzenia

Experimental: Part 2: Cohort Expansion, Combination, Breast, Trastuzumab (ECBT)
Cohort ECBT; Combination therapy partner administered per SOC at the approved dose.
Drug: Trastuzumab
600 mg every 3 weeks
Other Name: Herceptin

Experimental: Part 1a: Dose Escalation, Combination, Breast
eFT226 administered IV weekly in 21-day cycles. Fulvestrant will also be given. Dose escalations per protocol.
Drug: Fulvestrant
500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter
Other Name: Faslodex

Experimental: Part 1b Dose Escalation, Combination, Breast
eFT226 administered IV every other week in 14-day cycles. Fulvestrant will also be given. Dose escalations per protocol.
Drug: Fulvestrant
500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter
Other Name: Faslodex

Experimental: Part 2 Cohort Expansion, Combination, Breast, Fulvestrant, Cyclin D1
ECBF-D1; Combination therapy partner administered per SOC at the approved dose.
Drug: Fulvestrant
500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter
Other Name: Faslodex




Primary Outcome Measures :
  1. Parts 1a and 1b: MTD [ Time Frame: Through study completion, approximately 12 months ]
    determined by occurrence of first cycle DLTs within a 3+3 or 3+3+3 clinical trial design

  2. Parts 1a and 1b; incidence of AEs, serious adverse events (SAEs), and DLTs [ Time Frame: Through study completion, approximately 12 months ]
    according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

  3. Parts 1a and 1b: RP2D [ Time Frame: Through study completion, approximately 12 months ]
    determined by Incidence and type of DLTs

  4. Parts 1a and 1b: RP2D [ Time Frame: Through study completion, approximately 12 months ]
    determine by Incidence, type, and severity of AEs and SAEs graded as per NCI CTCAE

  5. Part 2: Objective Response Rate- Efficacy [ Time Frame: Through study completion, approximately 12 months ]
    defined as confirmed Complete Response (CR) or Partial Response (PR)

  6. Part 2: (Combination Cohorts) Determine MTD [ Time Frame: Through study completion, approximately 12 months ]
    determined by occurrence of first cycle Dose Limiting Toxicities (DLTs) within the study design

  7. Part 2: (Combination Cohorts) Incidence, type, and severity of AEs and SAEs [ Time Frame: Through study completion, approximately 12 months ]
    via adverse event monitoring

  8. Part 2: (Combination Cohorts) Determine RP2D [ Time Frame: 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)

  9. Part 2: Percent change in tumor dimensions of target lesions- Efficacy [ Time Frame: Through study completion, approximately 12 months ]
    calculated by the percentage change from baseline in the sum of the LD of target lesions

  10. Part 2: Time to Response (TTR)- Efficacy [ Time Frame: Through study completion, approximately 12 months ]
    defined as the interval from the start of study therapy to the first documentation of an objective response

  11. Part 2: Duration of Response (DOR)- Efficacy [ Time Frame: 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 :
  1. Parts 1a and 1b: Objective response [ Time Frame: Through study completion, approximately 12 months ]
    determined by confirmed CR or PR

  2. Parts 1a and 1b: Percent change in tumor dimensions of target lesions [ Time Frame: Through study completion, approximately 12 months ]
    calculated by the percentage change from baseline in the sum of the LD of target lesions

  3. Parts 1a and 1b: TTR [ Time Frame: Through study completion, approximately 12 months ]
    defined as the interval from the start of study therapy to the first documentation of an objective response

  4. Parts 1a and 1b: DOR [ Time Frame: 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

  5. Parts 1a and 1b: PFS [ Time Frame: 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

  6. Part 2: (Monotherapy and Combination Cohorts) Incidence and severity of AEs, SAEs, and additional safety parameters [ Time Frame: Through study completion, approximately 12 months ]
    via adverse event monitoring

  7. Part 2: Progression Free Survival [ Time Frame: 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

  8. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 [ Time Frame: Through study completion, approximately 12 months ]
    including area under the plasma concentration-time curve

  9. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 [ Time Frame: Through study completion, approximately 12 months ]
    including maximum concentration

  10. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 [ Time Frame: Through study completion, approximately 12 months ]
    including terminal phase rate constant

  11. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 [ Time Frame: Through study completion, approximately 12 months ]
    including estimated steady-state volume of distribution [Vss]

  12. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 [ Time Frame: Through study completion, approximately 12 months ]
    including half-life (t½)

  13. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 [ Time Frame: Through study completion, approximately 12 months ]
    including total body clearance

  14. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226including terminal state volume of distribution [ Time Frame: Through study completion, approximately 12 months ]
    including terminal state volume of distribution

  15. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 including terminal phase rate constant [ Time Frame: Through study completion, approximately 12 months ]
    including terminal phase rate constant



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 endocrine therapy in the advanced/metastatic disease setting.
    • Prior treatment has included a CDK4/6 inhibitor.
  • Tumor is ER+ (defined as ER IHC staining > 0%).

Cohort EMNK:

  • Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1/L1 agent, if appropriate.
  • Tumor has a known KRAS-activating mutation; Patients with KRAS G12C mutations are excluded.

Cohort EMBF:

  • 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 endocrine therapy in the advanced/metastatic disease setting, which may include combination therapy (eg, with a CDK4/6 inhibitor).
  • Tumor is ER+ (defined as ER IHC staining > 0%) and has FGFR amplification.

Cohort EMBH:

  • Patient has had prior chemotherapy, endocrine therapy, or other therapy as follows:

    • Minimum of one prior line of therapy for advanced/metastatic disease.
    • Minimum of one line of HER2-directed therapy Note: Prior treatment with CDK4/6 inhibitors is permitted.
  • Tumor is ER+ (defined as ER IHC staining > 0%) and HER2+ (defined as HER2 3+ IHC staining or HER2 2+ and FISH+).

Cohort ECNS:

  • Patient has histologically or cytologically confirmed stage IIIB (pleural or pericardial effusion) or stage IV NSCLC.
  • Patient has undergone treatment with platinum-based chemotherapy and an anti-PD-1/L1 agent, if appropriate. Note: Patients who have declined approved therapy(ies) or who per treating physician are not eligible for approved therapy(ies) (eg, due to intolerance) may be eligible following discussion with the Medical Monitor.
  • Tumor has a known G12C KRAS-activating mutation. Note: Patients who have been previously treated with KRAS-specific therapy are excluded.

Cohort ECBF:

  • 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 endocrine therapy in the advanced/metastatic disease setting.
    • Prior treatment has included a CDK4/6 inhibitor.
  • Tumor is ER+ (defined as ER IHC staining > 0%).

Cohort ECBF+A:

  • 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 endocrine therapy in the advanced/metastatic disease setting.
  • Tumor is ER+ (defined as ER IHC staining > 0%) and HER2- (defined as absence of HER2 3+ IHC staining and/or absence of FISH+).

Cohort ECBT:

  • Patient has progressed after treatment with at least one approved anti-HER2 agent and has been administered at least one line of chemotherapy.
  • Tumor is HER2+ (defined as HER2 3+ IHC staining or HER2 2+ and FISH+). Cohorts EMBF, EMBH, ECBF, ECBF+A: There is no limit on the number of lines of prior endocrine therapies.

Cohort ECBF-D1:

  • 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 endocrine therapy in the advanced/metastatic disease setting.
    • Prior treatment has included a CDK4/6 inhibitor.
  • Tumor is ER+ (defined as ER IHC staining > 0%).
  • Tumor has amplification of Cyclin D1 as determined by next generation sequencing or in situ hybridization.

Information from the National Library of Medicine

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


Contacts
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Contact: Mark Densel 858-925-8215 clinicaltrials@effector.com

Locations
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United States, California
University of Southern California Recruiting
Los Angeles, California, United States, 90033
Contact: Lorraine Martinez    323-865-3967    Lorraine.Martinez@med.usc.edu   
Principal Investigator: Anthony El-Khoueiry, MD         
Valkyrie Clinical Trials Recruiting
Los Angeles, California, United States, 90067
Contact: Chi Chesenge    310-704-1503    chichesenge@valkyrieclinicaltrials.com   
Principal Investigator: David Berz, MD         
Hoag Memorial Hospital Presbyterian Recruiting
Newport Beach, California, United States, 92663
Contact: Rosie Blancas    949-764-5543    Rosie.Blancas1@hoag.org   
Principal Investigator: Anthony El-Khouiery, MD         
Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Lisa Kody    650-498-8583    lkody@stanford.edu   
Principal Investigator: Jennifer Caswell-Jin, MD         
United States, Michigan
START Midwest Recruiting
Grand Rapids, Michigan, United States, 49546
Contact: Jade Blakeman    616-954-5554    Jade.Blakeman@startmidwest.com   
Principal Investigator: Manish Sharma, MD         
United States, New Jersey
Memorial Sloan Kettering Cancer Center Recruiting
Middletown, New Jersey, United States, 07748
Contact: Ezra Rosen       rosene1@mskcc.org   
Contact: Colleen Wenzel       WenzelC1@mskcc.org   
Principal Investigator: Ezra Rosen, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
Commack, New York, United States, 11725
Contact: Ezra Rosen, MD       rosene1@mskcc.org   
Contact: Colleen Wenzel       WenzelC1@mskcc.org   
Principal Investigator: Ezra Rosen, MD         
Memorial Sloan Kettering Cancer Center Recruiting
Harrison, New York, United States, 10604
Contact: Ezra Rosen       rosene1@mskcc.org   
Contact: Colleen Wenzel       WenzelC1@mskcc.org   
Principal Investigator: Ezra Rosen, MD         
Memorial Sloan Kettering Cancer Center- David H. Koch Center for Cancer Care Recruiting
New York, New York, United States, 11101
Contact: Ezra Rosen, MD       rosene1@mskcc.org   
Contact: Colleen Wenzel       WenzelC1@mskcc.org   
Principal Investigator: Ezra Rosen, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Raquel Montelongo    713-563-6049    rmontelongo@mdanderson.org   
Principal Investigator: Funda Meric-Bernstam, MD         
New Experimental Therapeutics of San Antonio - NEXT Oncology Recruiting
San Antonio, Texas, United States, 78229
Contact: Nicole Klein    210-580-9543    nklein@nextoncology.com   
Principal Investigator: David Sommerhalder, MD         
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Karina Castillo-Grady       Karina.CastilloGrady@usoncology.com   
Principal Investigator: Alexander Spira, MD         
Sponsors and Collaborators
Effector Therapeutics
Investigators
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Study Director: Douglas Warner, MD eFFECTOR Therapeutics, Inc.
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Responsible Party: Effector Therapeutics
ClinicalTrials.gov Identifier: NCT04092673    
Other Study ID Numbers: eFT226-0002
First Posted: September 17, 2019    Key Record Dates
Last Update Posted: November 18, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is not a plan to make IPD available

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms
Trastuzumab
Fulvestrant
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs