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

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

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