Evaluating eFT226 for advanced solid tumors

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

This study is testing a new drug called eFT226 to see if it can help people with advanced solid tumors, especially those with breast cancer who haven't responded to other treatments.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Effector Therapeutics (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 14 sites (Los Angeles, California and 13 other locations)
• Trial ID: NCT04092673 on ClinicalTrials.gov

What this trial studies

This clinical trial is a Phase 1-2, open-label study assessing the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of eFT226 in patients with selected advanced solid tumor malignancies. The study consists of a dose escalation phase to determine the recommended Phase 2 dose and maximum tolerated dose, followed by an expansion cohort to further evaluate the drug's efficacy and safety in various combinations. Patients with advanced breast cancer who are refractory or intolerant to standard of care therapies are specifically targeted in this trial.

Who should consider this trial

Good fit: Ideal candidates include adults with advanced breast cancer that is refractory or intolerant to prior therapies.

Not a fit: Patients with solid tumors that do not have a history of treatment failure with standard therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for patients with advanced solid tumors that have not responded to existing therapies.

How similar studies have performed: Other studies have shown promise with similar approaches targeting advanced solid tumors, indicating potential for success.

Eligibility 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.

Where this trial is running

Los Angeles, California and 13 other locations

• University of Southern California — Los Angeles, California, United States (Recruiting)
• Valkyrie Clinical Trials — Los Angeles, California, United States (Recruiting)
• Hoag Memorial Hospital Presbyterian — Newport Beach, California, United States (Completed)
• Stanford University — Palo Alto, California, United States (Recruiting)
• START Midwest — Grand Rapids, Michigan, United States (Recruiting)
• Comprehensive Cancer Centers of Nevada — Las Vegas, Nevada, United States (Completed)
• Memorial Sloan Kettering Cancer Center- Monmouth — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center- Commack — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center- Westchester — Harrison, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center- David H. Koch Center for Cancer Care — New York, New York, United States (Recruiting)
• University of Toledo Medical Center — Toledo, Ohio, United States (Completed)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)
• New Experimental Therapeutics of San Antonio - NEXT Oncology — San Antonio, Texas, United States (Completed)
• Virginia Cancer Specialists — Fairfax, Virginia, United States (Recruiting)

Study contacts

• Study coordinator: Mark Densel

Conditions Solid Tumor, Adult