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.