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.