A Study of LOXO-783 Administered as Monotherapy and in Combination with Anticancer Therapies for Patients with Advanced Breast Cancer and Other Solid Tumors with a PIK3CA H1047R Mutation

ENROLLING
Protocol # :
22-168
Conditions
Breast Cancer
Phase
I
Disease Sites
Healthy volunteer
Transplanted organ and tissue status, unspecified
Disease not specified
Neuroendocrine/Carcinoid
Gastroesophageal Junction
Gallbladder/Biliary
Other specified personal risk factors, not elsewhere classified
Lip, Oral Cavity and Pharynx
Esophagus
Stomach
Small Intestine
Colon
Rectum
Anus
Liver
Pancreas
Other Digestive Organ
Larynx
Lung
Other Respiratory and Intrathoracic Organs
Bones and Joints
Soft Tissue
Mycosis Fungoides
Other Skin
Breast
Cervix
Corpus Uteri
Ovary
Other Female Genital
Prostate
Other Male Genital
Urinary Bladder
Kidney
Other Urinary
Eye and Orbit
Brain and Nervous System
Thyroid
Unknown Sites
Ill-Defined Sites
Other Endocrine System
Donors
Kaposi's Sarcoma
Melanoma, Skin
Principal Investigator
Juric, Dejan
Site Research Nurses
Baldwin, Kayla
Blaikie, Anna, Rose
Boudreault, Teresa
Bowers, Jordan
Campbell, Margaret
Carr, Margaret, M.
Channell, Kelly
Cung, Connie
Daley, Alycia
Delrosso, Alexandria, P.
Ficociello, Samantha
Jeon, Maryangel, H.
Joyce, Margaret
Kasparian, Elizabeth
Kuhlman, Rachel
Loeser, Wendy
Lundin, Aishlinn
Lundquist, Debra
Ly, Christina
Mackey, Kathleen
McIntyre, Casandra
Orechia, Meghan
Patel, Nikita
Rutter, Morgan
Spriggs, Kristen
Sutcliffe, Shaun
Turbini, Victoria, L.

Trial Description

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 Requirements

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

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