Study of eFT226 in Subjects With Selected 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.