Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies

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.

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.

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.