A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors

Inclusion criteria

• Have advanced breast cancer or another solid tumor with the presence of a phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) H1047R mutation (or other Sponsor and safety review committee (SRC)-approved, activating PIK3CA mutations other than H1047R mutation)
• Have adequate archival tumor tissue sample available or be approved by the Sponsor for enrollment if no tumor sample is available.
• Have stopped all cancer treatment and have recovered from the major side effects
• Have adequate organ function, as measured by blood tests
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
• Patients must have

• Measurable disease

--- Patients with non-breast tumor types must have at least 1 measurable lesion

• Non-measurable bone disease (at least 1 bone lesion in breast cancer patients only)
• For patients with an estrogen receptor (ER)+ breast cancer diagnosis:

• If female, must be postmenopausal
• If male, must agree to use hormone suppression
• Phase 1a:

-- Dose escalation and backfill patients:

• Advanced solid tumor
• Patients may have had up to 5 prior regimens for advanced disease
• Phase 1b:

• Part A:

• ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease ---- Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required
• Part B:

• ER+/HER2- advanced breast cancer
• Patients may have had up to 2 prior regimens for advanced disease.
• Part C:

• ER+/HER2- advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease.

---- Prior CDK4/6 inhibitor therapy required.

• Have a diagnosis of diabetes mellitus Type 2
• Part D:

• Advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease.
• Part E:

• Advanced solid tumor
• Patients may have had up to 3 prior regimens for advanced disease advanced disease
• Part F:

• ER+/HER2- advanced breast cancer
• Patients may have had up to 5 prior regimens for advanced disease

• Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required

Exclusion criteria

• Medical Conditions

• Colorectal cancer
• Endometrial cancers with specific concurrent oncogenic alterations
• A history of known active or suspected

• Diabetes mellitus Type 1 or
• Diabetes mellitus Type 2 requiring antidiabetic medication (Phase 1a and all parts of Phase 1b except Part C).
• Serious concomitant systemic disorder
• Known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement.
• Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection, or other clinically significant active disease process
• Prior exposure to phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) inhibitor(s), except in certain circumstances