Breast Cancer
Conditions
Brief summary
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.
Interventions
DRUGLOXO-783
Oral
DRUGFulvestrant
Intramuscular
DRUGImlunestrant
Oral
DRUGAbemaciclib
Oral
DRUGAnastrozole, Exemestane, or Letrozole
Oral
DRUGPaclitaxel
Intravenous
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 a: To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of LOXO-783: Number of patients with dose-limiting toxicities (DLTs) | During the first 28-day cycle of LOXO-783 treatment | Number of patients with DLTs |
| Phase 1 a: To determine the MTD/RP2D of LOXO-783: Number of patients with DLT-equivalent toxicities | During the first 28-day cycle of LOXO-783 treatment | Number of patients with DLT-equivalent toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess the pharmacokinetics (PK) of LOXO-783: Area under the concentration versus time curve (AUC) | Up to 2 months | PK of LOXO-783: AUC |
| To assess the PK of LOXO-783: Maximum drug concentration (Cmax) | Up to 2 months | PK of LOXO-783: Cmax |
| To evaluate the preliminary antitumor activity of LOXO-783: Overall response rate (ORR) | Up to approximately 36 months or 3 years | ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) |
| To evaluate the preliminary antitumor activity of LOXO-783: Best overall response (BOR) | Up to approximately 36 months or 3 years | BOR per investigator assessed RECIST 1.1 |
| To evaluate the preliminary antitumor activity of LOXO-783: Duration of response (DOR) | Up to approximately 36 months or 3 years | DOR per investigator assessed RECIST 1.1 |
| To evaluate the preliminary antitumor activity of LOXO-783: Disease control rate (DCR) | Up to approximately 36 months or 3 years | DCR per investigator assessed RECIST 1.1 |
| To evaluate the preliminary antitumor activity of LOXO-783: Clinical benefit rate (CBR) | Up to approximately 36 months or 3 years | CBR per investigator assessed RECIST 1.1 |
| To evaluate the preliminary antitumor activity of LOXO-783: Time to response (TTR) | Up to approximately 36 months or 3 years | TTR per investigator assessed RECIST 1.1 |
| To evaluate the preliminary antitumor activity of LOXO-783: Progression free survival (PFS) | Up to approximately 36 months or 3 years | PFS per investigator assessed RECIST 1.1 |
| To evaluate the preliminary antitumor activity of LOXO-783: Overall survival (OS) | Up to approximately 36 months or 3 years | OS per investigator assessed RECIST 1.1 |
Countries
Australia, Belgium, China, France, Germany, Japan, Singapore, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Outcome results
None listed