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

Phase 1

Active, not recruiting

• Conditions: Breast Cancer
• Interventions: Drug: LOXO-783; Drug: Fulvestrant; Drug: Paclitaxel; Drug: Imlunestrant; Drug: Anastrozole, Exemestane, or Letrozole; Drug: Abemaciclib

• Registration Number: NCT05307705
• Lead Sponsor: Eli Lilly and Company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-03-25
• Study First Submitted QC: 2022-03-25
• Study First Posted: 2022-04-01
• Study Start: 2022-05-11
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-25
• Last Update Posted: 2025-06-27
• Primary Completion: 2025-12
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 400

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1B: Part A	Anastrozole, Exemestane, or Letrozole	LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally
Phase 1A: LOXO-783 Monotherapy Dose Escalation	LOXO-783	LOXO-783 administered orally
Phase 1B: Part A	LOXO-783	LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally
Phase 1B: Part A	Fulvestrant	LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally
Phase 1B: Part A	Imlunestrant	LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally
Phase 1B: Part B	Abemaciclib	LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally
Phase 1B: Part E	LOXO-783	LOXO-783 orally
Phase 1B: Part B	LOXO-783	LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally
Phase 1B: Part B	Imlunestrant	LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally
Phase 1B: Part B	Anastrozole, Exemestane, or Letrozole	LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally
Phase 1B: Part C	LOXO-783	LOXO-783 orally in combination with fulvestrant intramuscularly
Phase 1B: Part F	LOXO-783	Multiple randomized dose levels of LOXO-783 orally with fulvestrant intramuscularly
Phase 1B: Part D	LOXO-783	LOXO-783 orally in combination with paclitaxel intravenously
Phase 1B: Part B	Fulvestrant	LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally
Phase 1B: Part C	Fulvestrant	LOXO-783 orally in combination with fulvestrant intramuscularly
Phase 1B: Part D	Paclitaxel	LOXO-783 orally in combination with paclitaxel intravenously
Phase 1B: Part F	Fulvestrant	Multiple randomized dose levels of LOXO-783 orally with fulvestrant intramuscularly

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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: 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 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 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: Overall survival (OS)	Up to approximately 36 months or 3 years	OS per investigator assessed RECIST 1.1
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: Clinical benefit rate (CBR)	Up to approximately 36 months or 3 years	CBR per investigator assessed RECIST 1.1

Trial Locations

Locations (49)

Mayo Clinic of Scottsdale; 🇺🇸 Scottsdale, Arizona, United States

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

UCSF Medical Center at Mission Bay; 🇺🇸 San Francisco, California, United States

Stanford University Hospital; 🇺🇸 Stanford, California, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Winship Cancer Center Emory University; 🇺🇸 Atlanta, Georgia, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Washington University Medical School; 🇺🇸 Saint Louis, Missouri, United States

Memorial Sloan Kettering Cancer Center; 🇺🇸 New York, New York, United States

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