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

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-783. LOXO-783 may be used to treat breast cancer and other solid tumors that have a change in a particular gene (known as the PIK3CA gene). Participation could last up to 36 months (3 years) and possibly longer if the disease does not get worse.


Eligibility Criteria:
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