Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies

NCT ID: NCT04092673

Last Updated: 2024-05-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-25

Study Completion Date

2025-03-31

Brief Summary

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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

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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.

Conditions

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Solid Tumor, Adult

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Dose Escalation, 3+3, 3+3+3
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

eFT226

Intervention Type DRUG

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).

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

Cohort EMNK

Group Type EXPERIMENTAL

eFT226

Intervention Type DRUG

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).

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

Cohort EMBF

Group Type EXPERIMENTAL

eFT226

Intervention Type DRUG

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).

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

Cohort EMBH

Group Type EXPERIMENTAL

eFT226

Intervention Type DRUG

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).

Part 2: Cohort Expansion, Combination, Breast, Fulvestrant (ECBF)

Cohort ECBF; Combination therapy partner administered per SOC at the approved dose.

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter

Part 2: Cohort Expansion, Combination, NSCLC, Sotorasib (ECNS)

Cohort ECNS; Combination therapy partner administered per SOC at the approved dose.

Group Type EXPERIMENTAL

Sotorasib

Intervention Type DRUG

Recommended dosage: 960 mg orally once daily

Part 2: Cohort Expansion, Combination, Breast, Fulvestrant+Abemaciclib (ECBF+A)

Cohort ECBF+A; Combination therapy partner administered per SOC at the approved dose.

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter

Abemaciclib

Intervention Type DRUG

Dose in combination with fulvestrant: 150 mg twice daily

Part 2: Cohort Expansion, Combination, Breast, Trastuzumab (ECBT)

Cohort ECBT; Combination therapy partner administered per SOC at the approved dose.

Group Type EXPERIMENTAL

Trastuzumab

Intervention Type DRUG

600 mg every 3 weeks

Part 1a: Dose Escalation, Combination, Breast

eFT226 administered IV weekly in 21-day cycles. Fulvestrant will also be given. Dose escalations per protocol.

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter

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.

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter

Part 2 Cohort Expansion, Combination, Breast, Fulvestrant, Cyclin D1

ECBF-D1; Combination therapy partner administered per SOC at the approved dose.

Group Type EXPERIMENTAL

Fulvestrant

Intervention Type DRUG

500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter

Interventions

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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).

Intervention Type DRUG

Sotorasib

Recommended dosage: 960 mg orally once daily

Intervention Type DRUG

Fulvestrant

500 mg administered intramuscularly on Days 1, 15, 29, and once monthly thereafter

Intervention Type DRUG

Abemaciclib

Dose in combination with fulvestrant: 150 mg twice daily

Intervention Type DRUG

Trastuzumab

600 mg every 3 weeks

Intervention Type DRUG

Other Intervention Names

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Selective translation inhibitor Lumarkus Faslodex Verzenia Herceptin

Eligibility Criteria

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Exclusion Criteria

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Effector Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Douglas Warner, MD

Role: STUDY_DIRECTOR

EFFECTOR Therapeutics, Inc.

Locations

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University of Southern California

Los Angeles, California, United States

Site Status RECRUITING

Valkyrie Clinical Trials

Los Angeles, California, United States

Site Status RECRUITING

Hoag Memorial Hospital Presbyterian

Newport Beach, California, United States

Site Status COMPLETED

Stanford University

Palo Alto, California, United States

Site Status RECRUITING

START Midwest

Grand Rapids, Michigan, United States

Site Status RECRUITING

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status COMPLETED

Memorial Sloan Kettering Cancer Center- Monmouth

Middletown, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center- Commack

Commack, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center- Westchester

Harrison, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center- David H. Koch Center for Cancer Care

New York, New York, United States

Site Status RECRUITING

University of Toledo Medical Center

Toledo, Ohio, United States

Site Status COMPLETED

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

New Experimental Therapeutics of San Antonio - NEXT Oncology

San Antonio, Texas, United States

Site Status COMPLETED

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Mark Densel

Role: CONTACT

858-925-8215

Facility Contacts

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Xiomara Menendez

Role: primary

323-409-4638

Chemyn Cortez

Role: primary

559-360-3707

Kaushali Thakore-Shah

Role: primary

Abigail Van Kirk

Role: primary

616-954-5550 ext. 1824

Ezra Rosen

Role: primary

Colleen Wenzel

Role: backup

Ezra Rosen, MD

Role: primary

Colleen Wenzel

Role: backup

Ezra Rosen

Role: primary

Colleen Wenzel

Role: backup

Ezra Rosen, MD

Role: primary

Colleen Wenzel

Role: backup

Amanda Ekert

Role: primary

713-745-8074

Karina Castillo-Grady

Role: primary

703-280-5390

Other Identifiers

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eFT226-0002

Identifier Type: -

Identifier Source: org_study_id

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