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Solid Tumor, AdultPhase 1/2ZotatifinNCT04092673

Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies

A Phase 1/2 study testing eFT226, Sotorasib and Fulvestrant in people with Solid Tumor, Adult, run by Effector Therapeutics at 14 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumor, Adult
What is being tested?
eFT226, Sotorasib and Fulvestrant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
14 sitesUnited States
Study dates
25 Oct 2019to 31 Mar 2025
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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.

Trial locations and contacts

14 sites in 1 country.

Mark Densel contact

858-925-8215

clinicaltrials@effector.com

14 sites in 1 country

United States14 sites, 10 recruiting

  • Memorial Sloan Kettering Cancer Center- Commack

    Commack, New York, 11725

    Ezra Rosen, MD, rosene1@mskcc.org

    Colleen Wenzel, WenzelC1@mskcc.org

    Recruiting

  • Virginia Cancer Specialists

    Fairfax, Virginia, 22031

    Karina Castillo-Grady, 703-280-5390, Karina.CastilloGrady@usoncology.com

    Alexander Spira, MD

    Recruiting

  • START Midwest

    Grand Rapids, Michigan, 49546

    Abigail Van Kirk, 616-954-5550 ext. 1824, abigail.vankirk@startmidwest.com

    Manish Sharma, MD

    Recruiting

  • Memorial Sloan Kettering Cancer Center- Westchester

    Harrison, New York, 10604

    Ezra Rosen, rosene1@mskcc.org

    Colleen Wenzel, WenzelC1@mskcc.org

    Recruiting

  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Amanda Ekert, 713-745-8074, ACEckert@mdanderson.org

    Funda Meric-Bernstam, MD

    Recruiting

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89169

    Completed

  • University of Southern California

    Los Angeles, California, 90033

    Xiomara Menendez, 323-409-4638, menendez_x@med.usc.edu

    Anthony El-Khoueiry, MD

    Recruiting

  • Valkyrie Clinical Trials

    Los Angeles, California, 90067

    Chemyn Cortez, 559-360-3707, chemyn.cortez@valkyrieclinicaltrials.com

    David Berz, MD

    Recruiting

  • Memorial Sloan Kettering Cancer Center- Monmouth

    Middletown, New Jersey, 07748

    Ezra Rosen, rosene1@mskcc.org

    Colleen Wenzel, WenzelC1@mskcc.org

    Recruiting

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

    New York, New York, 11101

    Ezra Rosen, MD, rosene1@mskcc.org

    Colleen Wenzel, WenzelC1@mskcc.org

    Recruiting

  • Hoag Memorial Hospital Presbyterian

    Newport Beach, California, 92663

    Completed

  • Stanford University

    Palo Alto, California, 94304

    Kaushali Thakore-Shah, kthakore@stanford.edu

    Jennifer Caswell-Jin, MD

    Recruiting

  • New Experimental Therapeutics of San Antonio - NEXT Oncology

    San Antonio, Texas, 78229

    Completed

  • University of Toledo Medical Center

    Toledo, Ohio, 43614

    Completed

Other trials in United States

About this study

Official title: A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Intravenous Zotatifin (eFT226) in Subjects With Selected Advanced Solid Tumor Malignancies

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.

Read the 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.

Being tested
eFT226, Sotorasib, Fulvestrant, Abemaciclib, Trastuzumab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • eFT226Drug

    Also called Selective translation inhibitor

    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).

  • SotorasibDrug

    Also called Lumarkus

    Recommended dosage: 960 mg orally once daily

  • FulvestrantDrug

    Also called Faslodex

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

  • AbemaciclibDrug

    Also called Verzenia

    Dose in combination with fulvestrant: 150 mg twice daily

  • TrastuzumabDrug

    Also called Herceptin

    600 mg every 3 weeks

Study groups in NCT04092673
Study groupRoleWhat they receive
Part 1: Sequential escalation (Completed)ExperimentaleFT226 administered IV weekly in 21-day cycles; dose escalated in sequential cohorts after subjects enrolled in a given cohort have completed DLT evaluation period.
Receives: Drug: eFT226
Part 2: Cohort Expansion, Monotherapy, NSCLC, KRAS (EMNK)ExperimentalCohort EMNK
Receives: Drug: eFT226
Part 2: Cohort Expansion, Monotherapy, Breast, FGFR (EMBF)ExperimentalCohort EMBF
Receives: Drug: eFT226
Part 2: Cohort Expansion, Monotherapy, Breast, HER2 (EMBH)ExperimentalCohort EMBH
Receives: Drug: eFT226
Part 2: Cohort Expansion, Combination, Breast, Fulvestrant (ECBF)ExperimentalCohort ECBF; Combination therapy partner administered per SOC at the approved dose.
Receives: Drug: Fulvestrant
Part 2: Cohort Expansion, Combination, NSCLC, Sotorasib (ECNS)ExperimentalCohort ECNS; Combination therapy partner administered per SOC at the approved dose.
Receives: Drug: Sotorasib
Part 2: Cohort Expansion, Combination, Breast, Fulvestrant+Abemaciclib (ECBF+A)ExperimentalCohort ECBF+A; Combination therapy partner administered per SOC at the approved dose.
Receives: Drug: Fulvestrant; Drug: Abemaciclib
Part 2: Cohort Expansion, Combination, Breast, Trastuzumab (ECBT)ExperimentalCohort ECBT; Combination therapy partner administered per SOC at the approved dose.
Receives: Drug: Trastuzumab
Part 1a: Dose Escalation, Combination, BreastExperimentaleFT226 administered IV weekly in 21-day cycles. Fulvestrant will also be given. Dose escalations per protocol.
Receives: Drug: Fulvestrant
Part 1b Dose Escalation, Combination, BreastExperimentaleFT226 administered IV every other week in 14-day cycles. Fulvestrant will also be given. Dose escalations per protocol.
Receives: Drug: Fulvestrant
Part 2 Cohort Expansion, Combination, Breast, Fulvestrant, Cyclin D1ExperimentalECBF-D1; Combination therapy partner administered per SOC at the approved dose.
Receives: Drug: Fulvestrant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Parts 1a and 1b: MTD

    determined by occurrence of first cycle DLTs within a 3+3 or 3+3+3 clinical trial design

    Measured: Through study completion, approximately 12 months

  2. Parts 1a and 1b; incidence of AEs, serious adverse events (SAEs), and DLTs

    according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)

    Measured: Through study completion, approximately 12 months

  3. Parts 1a and 1b: RP2D

    determined by Incidence and type of DLTs

    Measured: Through study completion, approximately 12 months

  4. Parts 1a and 1b: RP2D

    determine by Incidence, type, and severity of AEs and SAEs graded as per NCI CTCAE

    Measured: Through study completion, approximately 12 months

  5. Part 2: Objective Response Rate- Efficacy

    defined as confirmed Complete Response (CR) or Partial Response (PR)

    Measured: Through study completion, approximately 12 months

  6. Part 2: (Combination Cohorts) Determine MTD

    determined by occurrence of first cycle Dose Limiting Toxicities (DLTs) within the study design

    Measured: Through study completion, approximately 12 months

  7. Part 2: (Combination Cohorts) Incidence, type, and severity of AEs and SAEs

    via adverse event monitoring

    Measured: Through study completion, approximately 12 months

  8. Part 2: (Combination Cohorts) Determine RP2D

    determined by incidence and type of DLTs, and incidence, type, and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Measured: Through study completion, approximately 12 months

  9. Part 2: Percent change in tumor dimensions of target lesions- Efficacy

    calculated by the percentage change from baseline in the sum of the LD of target lesions

    Measured: Through study completion, approximately 12 months

  10. Part 2: Time to Response (TTR)- Efficacy

    defined as the interval from the start of study therapy to the first documentation of an objective response

    Measured: Through study completion, approximately 12 months

  11. Part 2: Duration of Response (DOR)- Efficacy

    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

    Measured: Through study completion, approximately 12 months

Secondary outcomes (15)

  1. Parts 1a and 1b: Objective response

    determined by confirmed CR or PR

    Measured: Through study completion, approximately 12 months

  2. Parts 1a and 1b: Percent change in tumor dimensions of target lesions

    calculated by the percentage change from baseline in the sum of the LD of target lesions

    Measured: Through study completion, approximately 12 months

  3. Parts 1a and 1b: TTR

    defined as the interval from the start of study therapy to the first documentation of an objective response

    Measured: Through study completion, approximately 12 months

  4. Parts 1a and 1b: DOR

    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

    Measured: Through study completion, approximately 12 months

  5. Parts 1a and 1b: PFS

    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

    Measured: Through study completion, approximately 12 months

  6. Part 2: (Monotherapy and Combination Cohorts) Incidence and severity of AEs, SAEs, and additional safety parameters

    via adverse event monitoring

    Measured: Through study completion, approximately 12 months

  7. Part 2: Progression Free Survival

    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

    Measured: Through study completion, approximately 12 months

  8. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226

    including area under the plasma concentration-time curve

    Measured: Through study completion, approximately 12 months

  9. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226

    including maximum concentration

    Measured: Through study completion, approximately 12 months

  10. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226

    including terminal phase rate constant

    Measured: Through study completion, approximately 12 months

  11. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226

    including estimated steady-state volume of distribution [Vss]

    Measured: Through study completion, approximately 12 months

  12. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226

    including half-life (t½)

    Measured: Through study completion, approximately 12 months

  13. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226

    including total body clearance

    Measured: Through study completion, approximately 12 months

  14. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226including terminal state volume of distribution

    including terminal state volume of distribution

    Measured: Through study completion, approximately 12 months

  15. Evaluate plasma Pharmacokinetic (PK) parameters of eFT226 including terminal phase rate constant

    including terminal phase rate constant

    Measured: Through study completion, approximately 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Sep 2019
  2. Study start25 Oct 2019
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion31 Mar 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
Dose Escalation, 3+3, 3+3+3
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04092673
Sponsor's protocol ID
eFT226-0002
Acronym
Zotatifin
Status last verified
May 2024
First submitted
10 Sep 2019
Last updated
21 May 2024
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: There is not a plan to make IPD available

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing eFT226, Sotorasib and Fulvestrant in people with Solid Tumor, Adult, run by Effector Therapeutics at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 21 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Mark Densel (858-925-8215, clinicaltrials@effector.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Parts 1a and 1b: MTD (time frame: Through study completion, approximately 12 months). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04092673.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2024.

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