Recruiting
Phase 1
Phase 2

eFT226

Sponsor:

Effector Therapeutics

Code:

NCT04092673

Conditions

Solid Tumor, Adult

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

eFT226

Sotorasib

Fulvestrant

Abemaciclib

Trastuzumab

Study Details

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.

Conditions

Solid Tumor, Adult

Study ID

NCT04092673

Start date

Oct 25, 2019

Status verified date

May, 2024

Completion date

Mar 31, 2025

Anticipated

Primary completion date

Dec 31, 2024

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

30 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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

Cohort EMNK

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

Cohort EMBF

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

Cohort EMBH

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

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

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

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

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

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

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

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

experimental: Part 1a: Dose Escalation, Combination, Breast

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

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.

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

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

Interventions

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).

Sotorasib

Recommended dosage: 960 mg orally once daily

Fulvestrant

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

Abemaciclib

Dose in combination with fulvestrant: 150 mg twice daily

Trastuzumab

600 mg every 3 weeks

Primary outcome measure

  • Parts 1a and 1b: MTD [ Time Frame: Through study completion, approximately 12 months ]
  • Parts 1a and 1b; incidence of AEs, serious adverse events (SAEs), and DLTs [ Time Frame: Through study completion, approximately 12 months ]
  • Parts 1a and 1b: RP2D [ Time Frame: Through study completion, approximately 12 months ]
  • Parts 1a and 1b: RP2D [ Time Frame: Through study completion, approximately 12 months ]
  • Part 2: Objective Response Rate- Efficacy [ Time Frame: Through study completion, approximately 12 months ]
  • Part 2: (Combination Cohorts) Determine MTD [ Time Frame: Through study completion, approximately 12 months ]
  • Part 2: (Combination Cohorts) Incidence, type, and severity of AEs and SAEs [ Time Frame: Through study completion, approximately 12 months ]
  • Part 2: (Combination Cohorts) Determine RP2D [ Time Frame: Through study completion, approximately 12 months ]
  • Part 2: Percent change in tumor dimensions of target lesions- Efficacy [ Time Frame: Through study completion, approximately 12 months ]
  • Part 2: Time to Response (TTR)- Efficacy [ Time Frame: Through study completion, approximately 12 months ]
  • Part 2: Duration of Response (DOR)- Efficacy [ Time Frame: Through study completion, approximately 12 months ]

Central Contacts and Locations

Central contacts

Mark Densel

858-925-8215clinicaltrials@effector.com

Locations

University of Southern California

Recruiting

Los Angeles, California, United States, 90033

Contacts

Xiomara Menendez

323-409-4638menendez_x@med.usc.edu

Principal Investigator:

Anthony El-Khoueiry, MD

Valkyrie Clinical Trials

Recruiting

Los Angeles, California, United States, 90067

Contacts

Chemyn Cortez

559-360-3707chemyn.cortez@valkyrieclinicaltrials.com

Principal Investigator:

David Berz, MD

Stanford University

Recruiting

Palo Alto, California, United States, 94304

Contacts

Kaushali Thakore-Shah

kthakore@stanford.edu

Principal Investigator:

Jennifer Caswell-Jin, MD

START Midwest

Recruiting

Grand Rapids, Michigan, United States, 49546

Contacts

Abigail Van Kirk

616-954-5550abigail.vankirk@startmidwest.com

Principal Investigator:

Manish Sharma, MD

Memorial Sloan Kettering Cancer Center- Monmouth

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Ezra Rosen

rosene1@mskcc.org

Colleen Wenzel

WenzelC1@mskcc.org

Principal Investigator:

Ezra Rosen, MD

Memorial Sloan Kettering Cancer Center- Commack

Recruiting

Commack, New York, United States, 11725

Contacts

Ezra Rosen, MD

rosene1@mskcc.org

Colleen Wenzel

WenzelC1@mskcc.org

Principal Investigator:

Ezra Rosen, MD

Memorial Sloan Kettering Cancer Center- Westchester

Recruiting

Harrison, New York, United States, 10604

Contacts

Ezra Rosen

rosene1@mskcc.org

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

Contacts

Ezra Rosen, MD

rosene1@mskcc.org

Colleen Wenzel

WenzelC1@mskcc.org

Principal Investigator:

Ezra Rosen, MD

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Amanda Ekert

713-745-8074ACEckert@mdanderson.org

Principal Investigator:

Funda Meric-Bernstam, MD

Virginia Cancer Specialists

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Karina Castillo-Grady

703-280-5390Karina.CastilloGrady@usoncology.com

Principal Investigator:

Alexander Spira, MD

More Information

Sponsor

Effector Therapeutics

Last update posted

May 21, 2024

Last verified

May, 2024

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Effector Therapeutics on 2024-05-21.