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 PIK3CA H1047R mutation (or other Sponsor and 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 one bone lesion in breast cancer patients only)

For patients with an 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+/HER2- advanced breast cancer

Patients may have had up to 2 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

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 PI3K/AKT/mTOR inhibitor(s), except in certain circumstances