Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies

NCT04092673 | Recruiting Phase 1 FDA Drug

• 1 other identifier: eFT226-0002
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 14

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

Outcome Measures

Primary Outcomes (11)

• Parts 1a and 1b: MTD

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

  Through study completion, approximately 12 months

• 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)

  Through study completion, approximately 12 months

• Parts 1a and 1b: RP2D

  determined by Incidence and type of DLTs

  Through study completion, approximately 12 months

• Parts 1a and 1b: RP2D

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

  Through study completion, approximately 12 months

• Part 2: Objective Response Rate- Efficacy

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

  Through study completion, approximately 12 months

• Part 2: (Combination Cohorts) Determine MTD

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

  Through study completion, approximately 12 months

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

  via adverse event monitoring

  Through study completion, approximately 12 months

• 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)

  Through study completion, approximately 12 months

• 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

  Through study completion, approximately 12 months

• 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

  Through study completion, approximately 12 months

• 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

  Through study completion, approximately 12 months

Secondary Outcomes (15)

• Parts 1a and 1b: Objective response

  Through study completion, approximately 12 months

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

  Through study completion, approximately 12 months

• Parts 1a and 1b: TTR

  Through study completion, approximately 12 months

• Parts 1a and 1b: DOR

  Through study completion, approximately 12 months

• Parts 1a and 1b: PFS

  Through study completion, approximately 12 months

Study Arms (11)

Part 1: Sequential escalation (Completed)

EXPERIMENTAL

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

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

EXPERIMENTAL

Cohort EMNK

Drug: eFT226

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

EXPERIMENTAL

Cohort EMBF

Drug: eFT226

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

EXPERIMENTAL

Cohort EMBH

Drug: eFT226

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

EXPERIMENTAL

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

Drug: Fulvestrant

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

EXPERIMENTAL

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

Drug: Sotorasib

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

EXPERIMENTAL

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

Drug: Fulvestrant; Drug: Abemaciclib

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

EXPERIMENTAL

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

Drug: Trastuzumab

Part 1a: Dose Escalation, Combination, Breast

EXPERIMENTAL

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

Drug: Fulvestrant

Part 1b Dose Escalation, Combination, Breast

EXPERIMENTAL

eFT226 administered IV every other week in 14-day cycles. Fulvestrant will also be given. Dose escalations per protocol.

Drug: Fulvestrant

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

EXPERIMENTAL

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

Drug: Fulvestrant

Interventions

eFT226 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).

Also known as: Selective translation inhibitor

Part 1: Sequential escalation (Completed); Part 2: Cohort Expansion, Monotherapy, Breast, FGFR (EMBF); Part 2: Cohort Expansion, Monotherapy, Breast, HER2 (EMBH); Part 2: Cohort Expansion, Monotherapy, NSCLC, KRAS (EMNK)

Sotorasib DRUG

Recommended dosage: 960 mg orally once daily

Also known as: Lumarkus

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

Fulvestrant DRUG

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

Also known as: Faslodex

Part 1a: Dose Escalation, Combination, Breast; Part 1b Dose Escalation, Combination, Breast; Part 2 Cohort Expansion, Combination, Breast, Fulvestrant, Cyclin D1; Part 2: Cohort Expansion, Combination, Breast, Fulvestrant (ECBF); Part 2: Cohort Expansion, Combination, Breast, Fulvestrant+Abemaciclib (ECBF+A)

Abemaciclib DRUG

Dose in combination with fulvestrant: 150 mg twice daily

Also known as: Verzenia

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

Trastuzumab DRUG

600 mg every 3 weeks

Also known as: Herceptin

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Effector Therapeutics: lead

Study Sites (14)

University of Southern California

Los Angeles, California, 90033, United States

RECRUITING

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

RECRUITING

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

COMPLETED

Stanford University

Palo Alto, California, 94304, United States

RECRUITING

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

COMPLETED

Memorial Sloan Kettering Cancer Center- Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Cancer Center- Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Cancer Center- Westchester

Harrison, New York, 10604, United States

RECRUITING

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

New York, New York, 11101, United States

RECRUITING

University of Toledo Medical Center

Toledo, Ohio, 43614, United States

COMPLETED

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

New Experimental Therapeutics of San Antonio - NEXT Oncology

San Antonio, Texas, 78229, United States

COMPLETED

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

MeSH Terms

Interventions

sotorasib; Fulvestrant; abemaciclib; Trastuzumab

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Douglas Warner, MD

  EFFECTOR Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Mark Densel

CONTACT

858-925-8215; clinicaltrials@effector.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose Escalation, 3+3, 3+3+3

Study Record Dates

• First Submitted: September 10, 2019
• First Posted: September 17, 2019
• Study Start: October 25, 2019
• Primary Completion: December 31, 2024
• Study Completion: March 31, 2025
• Last Updated: May 21, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)