A Study of LOXO-783 in Patients With Breast Cancer/Other Solid Tumors (PIKASSO-01)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: LOXO-783; Drug: Fulvestrant; Drug: Imlunestrant; Drug: Abemaciclib; Drug: Anastrozole, Exemestane, or Letrozole

• Study Type: Interventional
• Enrollment (Actual): 193
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Adelaide, Australia, 5000
    • Cancer Research SA
  • East Melbourne, Australia, 3002
    • Peter Maccallum Cancer Institute Erb
  • Sydney, Australia, 2010
    • St Vincent's Hospital
• Belgium
  • Anderlecht, Belgium, 1070
    • Institut Jules Bordet
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
• Canada
  • Toronto, Canada, M5G 2M9
    • Princess Margaret Hospital (Hong Kong)
  • Vancouver, Canada, V5Z4E6
    • Bc Cancer Vancouver
• China
  • Beijing, China, 100036
    • Beijing Cancer Hospital
  • Nanchang, China, 330009
    • The Third Hospital of Nanchang
  • Shanghai, China, 200032
    • Fudan University Shanghai Cancer Center
• France
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Paris, France, 75248
    • Institut Curie
  • Saint-Herblain, France, 44805
    • Institut de Cancerologie de L'Ouest
  • Strasbourg, France, 67033
    • ICANS_Institut de Cancerologie Strasbourg Europe
  • Villejuif, France, 94805
    • Gustave Roussy
• Germany
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen
• Japan
  • Chūōku, Japan, 104-0045
    • National Cancer Center Hospital
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Kōtō City, Japan, 135-8550
    • The Cancer Institute Hospital of Jfcr
  • Nagoya, Japan, 464-8681
    • Aichi Cancer Center Hospital
• Singapore
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore
• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 5505
    • Asan Medical Center
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebrón
  • Barcelona, Spain, 08028
    • Hospital Universitario Quiron Dexeus
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Pozuelo de Alarcón, Spain, 28223
    • Hospital Quirónsalud Madrid
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario De Valencia
  • Valencia, Spain, 46015
    • Hospital Arnau de Vilanova Valencia
• United Kingdom
  • London, United Kingdom, SW3 6JJ
    • Royal Marsden NHS Trust
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital (Sutton)
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic of Scottsdale
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • San Francisco, California, United States, 94158
      • UCSF Medical Center at Mission Bay
    • Stanford, California, United States, 94305
      • Stanford University Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Center Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0002
      • Mayo Clinic
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University Medical School
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • Rochester, New York, United States, 14642
      • Wilmot Cancer Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology-Baylor Charles A. Sammons Cancer Center
    • Dallas, Texas, United States, 75390-8884
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • South Texas Accelerated Research Therapeutics (START)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1A: LOXO-783 Monotherapy Dose Escalation; LOXO-783 administered orally	Drug: LOXO-783; Oral; Other Names: LY3849524
Experimental: Phase 1B: Part B; LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally	Drug: LOXO-783; Oral; Other Names: LY3849524; Drug: Fulvestrant; Intramuscular; Drug: Imlunestrant; Oral; Other Names: LY3484356; Drug: Abemaciclib; Oral; Other Names: LY2835219; Drug: Anastrozole, Exemestane, or Letrozole; Oral
Experimental: Phase 1B: Part C; LOXO-783 orally in combination with fulvestrant intramuscularly	Drug: LOXO-783; Oral; Other Names: LY3849524; Drug: Fulvestrant; Intramuscular
Experimental: Phase 1B: Part D; LOXO-783 orally in combination with paclitaxel intravenously	Drug: Paclitaxel; Intravenous; Drug: LOXO-783; Oral; Other Names: LY3849524
Experimental: Phase 1B: Part E; LOXO-783 orally	Drug: LOXO-783; Oral; Other Names: LY3849524
Experimental: Phase 1B: Part A; LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally	Drug: LOXO-783; Oral; Other Names: LY3849524; Drug: Fulvestrant; Intramuscular; Drug: Imlunestrant; Oral; Other Names: LY3484356; Drug: Anastrozole, Exemestane, or Letrozole; Oral
Experimental: Phase 1B: Part F; Multiple randomized dose levels of LOXO-783 orally with fulvestrant intramuscularly	Drug: LOXO-783; Oral; Other Names: LY3849524; Drug: Fulvestrant; Intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 a: To determine the MTD/RP2D of LOXO-783: Number of patients with DLT-equivalent toxicities	Number of patients with DLT-equivalent toxicities	During the first 28-day cycle of LOXO-783 treatment
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)	Number of patients with DLTs	During the first 28-day cycle of LOXO-783 treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the pharmacokinetics (PK) of LOXO-783: Area under the concentration versus time curve (AUC)	PK of LOXO-783: AUC	Up to 2 months
To assess the PK of LOXO-783: Maximum drug concentration (Cmax)	PK of LOXO-783: Cmax	Up to 2 months
To evaluate the preliminary antitumor activity of LOXO-783: Best overall response (BOR)	BOR per investigator assessed RECIST 1.1	Up to approximately 36 months or 3 years
To evaluate the preliminary antitumor activity of LOXO-783: Duration of response (DOR)	DOR per investigator assessed RECIST 1.1	Up to approximately 36 months or 3 years
To evaluate the preliminary antitumor activity of LOXO-783: Disease control rate (DCR)	DCR per investigator assessed RECIST 1.1	Up to approximately 36 months or 3 years
To evaluate the preliminary antitumor activity of LOXO-783: Clinical benefit rate (CBR)	CBR per investigator assessed RECIST 1.1	Up to approximately 36 months or 3 years
To evaluate the preliminary antitumor activity of LOXO-783: Time to response (TTR)	TTR per investigator assessed RECIST 1.1	Up to approximately 36 months or 3 years
To evaluate the preliminary antitumor activity of LOXO-783: Progression free survival (PFS)	PFS per investigator assessed RECIST 1.1	Up to approximately 36 months or 3 years
To evaluate the preliminary antitumor activity of LOXO-783: Overall survival (OS)	OS per investigator assessed RECIST 1.1	Up to approximately 36 months or 3 years
To evaluate the preliminary antitumor activity of LOXO-783: Overall response rate (ORR)	ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)	Up to approximately 36 months or 3 years

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Loxo Oncology, Inc.
• Investigators: Study Director: Call 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

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: March 25, 2022
• First Submitted That Met QC Criteria: March 25, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): April 20, 2026
• Last Update Submitted That Met QC Criteria: April 17, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Polycyclic Compounds; Taxoids; Cyclodecanes; Diterpenes; Steroids; Fused-Ring Compounds; Nitriles; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Triazoles; Letrozole; Fulvestrant; Anastrozole; Paclitaxel; abemaciclib; exemestane; Imlunestrant
• Other Study ID Numbers: 18394; LOXO-PIK-21001 (Other Identifier: Eli Lilly and Company); J4C-OX-JZUA (Other Identifier: Eli Lilly and Company); 2022-000175-40 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No