A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer or Endometrial Cancer

NCT04188548 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: 17502J2J-MC-JZLA2019-003581-41
• Study Type: interventional
• Target: 500
• Locations: 8 countries
• Sites: 74

Brief Summary

The reason for this study is to see if the study drug LY3484356 alone or in combination with other anticancer therapies is safe and effective in participants with advanced or metastatic breast cancer or endometrial cancer.

Conditions

Breast Cancer; Advanced Breast Cancer; Metastatic Breast Cancer; Endometrial Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Dose Limiting Toxicities (DLTs) and DLT-Equivalent Toxicities

  Number of Participants with DLTs and DLT-Equivalent Toxicities

  Baseline through Cycle 1 (21/28 Day Cycle)

Secondary Outcomes (9)

• Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY3484356

  Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)

• PK: Maximum Concentration (Cmax) of LY3484356

  Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)

• PK: AUC of LY3484356 in Combination with Other Anticancer Therapies

  Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)

• PK: Cmax of LY3484356 in Combination with Other Anticancer Therapies

  Predose Cycle 1 Day 1 through Predose Cycle 2 Day 1 (21/28 Day Cycles)

• Overall Response Rate (ORR): Percentage of Participants with Confirmed Complete Response (CR) or Partial Response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Baseline through Disease Progression or Death (Estimated up to 28 Months)

Study Arms (8)

Dose Escalation LY3484356

EXPERIMENTAL

LY3484356 given orally.

Drug: LY3484356

Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI

EXPERIMENTAL

LY3484356 and abemaciclib given orally in combination with or without Aromatase Inhibitor (AI) of physician's choice (Anastrozole, Exemestane, or Letrozole) administered orally.

Drug: LY3484356; Drug: Abemaciclib; Drug: Aromatase Inhibitor (AI)

Part B: Dose Expansion: Cohort E3: LY3484356

EXPERIMENTAL

LY3484356 given orally.

Drug: LY3484356

Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus

EXPERIMENTAL

LY3484356 and everolimus given orally.

Drug: LY3484356; Drug: Everolimus

Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib

EXPERIMENTAL

LY3484356 and alpelisib given orally.

Drug: LY3484356; Drug: Alpelisib

Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib

EXPERIMENTAL

LY3484356 administered orally in combination with trastuzumab intravenously with or without Abemaciclib.

Drug: LY3484356; Drug: Abemaciclib; Drug: Trastuzumab

Part D: Dose Expansion: LY3484356 +/- Abemaciclib

EXPERIMENTAL

LY3484356 and Abemaciclib given orally with trastuzumab administered intravenously.

Drug: LY3484356; Drug: Abemaciclib

Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab

EXPERIMENTAL

LY3484356 administered orally in combination with trastuzumab and pertuzumab administered intravenously.

Drug: LY3484356; Drug: Trastuzumab; Drug: Pertuzumab

Interventions

LY3484356 DRUG

Administered orally

Also known as: Imlunestrant

Dose Escalation LY3484356; Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI; Part B: Dose Expansion: Cohort E3: LY3484356; Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus; Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib; Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib; Part D: Dose Expansion: LY3484356 +/- Abemaciclib; Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab

Abemaciclib DRUG

Administered orally

Also known as: LY2835219

Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI; Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib; Part D: Dose Expansion: LY3484356 +/- Abemaciclib

Everolimus DRUG

Administered orally

Part B: Dose Expansion: Cohort E4: LY3484356 + Everolimus

Alpelisib DRUG

Administered orally

Part B: Dose Expansion: Cohort E5: LY3484356 + Alpelisib

Trastuzumab DRUG

Administered intravenously

Part C:Dose Expansion: LY3484356 + Trastuzumab +/- Abemaciclib; Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab

Aromatase Inhibitor (AI) DRUG

Anastrozole or Exemestane or Letrozole administered orally (physician choice)

Part A: Dose Expansion: LY3484356 + Abemaciclib +/- AI

Pertuzumab DRUG

Administered intravenously

Part E: Dose Expansion: LY3484356 + Trastuzumab + Pertuzumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All study parts:
• Participants must be willing to provide adequate archival tissue sample
• Participants must be willing to use highly effective birth control
• Participants must have adequate organ function
• Participants must be able to swallow capsules
• Dose escalation- Participants must have one of the following:
• Parts A and B: ER+ HER2- breast cancer with evidence of locally advanced unresectable or metastatic disease who have had the following:
• Part A: may have had up to 1 prior regimen of any kind for in the advanced/metastatic setting and no prior cyclin-dependent kinase 4/6 (CDK4/6) inhibitor therapy.
• Part B: may have had up to 2 prior regimens, no more than 1 of which may be endocrine therapy in the advanced/metastatic setting, and must have received a prior CDK4/6 inhibitor
• Cohort E4: No prior everolimus.
• Cohort E5: No prior alpelisib and must have a phosphatidylinositol 3-kinase catalytic α (PIK3Cα) mutation as determined by local testing.
• Part C: ER+, human epidermal growth factor receptor 2 positive (HER2+) breast cancer with evidence of locally advanced unresectable or metastatic disease who have had at least 2 HER2-directed therapies in any setting.
• Part D: ER+, EEC that has progressed after platinum containing chemotherapy and no prior fulvestrant or aromatase inhibitor therapy.
• Part E: ER+ and HER2+ breast cancer with evidence of locally advanced, unresectable, or metastatic disease.
• Part E: Participants must have received induction taxane chemotherapy combined with trastuzumab + pertuzumab as first-line treatment for advanced/metastatic disease and must not have progressed on this regimen.

You may not qualify if:

• Participants must not have certain infections such as hepatitis or tuberculosis or HIV that are not well controlled
• Participants must not have another serious medical condition
• Participants must not have cancer of the central nervous system that is unstable
• Participants must not be pregnant or breastfeeding

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (74)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Mayo Clinic in Arizona - Phoenix

Phoenix, Arizona, 85054, United States

Location

Highlands Oncology Group

Springdale, Arkansas, 72762, United States

Location

Beverly Hills Cancer Center

Beverly Hills, California, 90211, United States

Location

University of California, Irvine

Orange, California, 92868, United States

Location

UCSF Medical Center at Mission Bay

San Francisco, California, 94158, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224, United States

Location

Lake Nona DDU

Orlando, Florida, 32827, United States

Location

Winship Cancer Center Emory University

Atlanta, Georgia, 30322, United States

Location

Community Cancer Center North

Indianapolis, Indiana, 46250, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Minnesota Oncology/Hematology PA

Minneapolis, Minnesota, 55404, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering - Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Cancer Center

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Wilmot Cancer Institute

Rochester, New York, 14642, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Health Sciences Center, Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Asante Rogue Regional Medical Center

Medford, Oregon, 97504, United States

Location

UPMC Hillman Cancer Center Harrisburg

Harrisburg, Pennsylvania, 17109, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Vanderbilt Health One Hundred Oaks

Nashville, Tennessee, 37067, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

Tennessee Oncology Nashville

Nashville, Tennessee, 37203, United States

Location

UT Southwestern Med Center

Dallas, Texas, 75390-9179, United States

Location

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 77380, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229-3307, United States

Location

Minnesota Oncology/Hematology PA

The Woodlands, Texas, 77380, United States

Location

Oncology and Hematology Associates of Southwest Virginia Inc

The Woodlands, Texas, 77380, United States

Location

Texas Oncology - San Antonio Medical Center

The Woodlands, Texas, 77380, United States

Location

US Oncology

The Woodlands, Texas, 77380, United States

Location

USO-Rocky Mountain Cancer Center

The Woodlands, Texas, 77380, United States

Location

Texas Oncology - Tyler

Tyler, Texas, 75702, United States

Location

The University of Vermont Medical Center Inc.

Burlington, Vermont, 05401, United States

Location

Inova Schar Cancer Institute

Fairfax, Virginia, 22031, United States

Location

Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Cancer Research SA

Adelaide, South Australia, 5000, Australia

Location

Breast Cancer Research Centre-WA

Nedlands, Western Australia, 6009, Australia

Location

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

Location

Antwerp University Hospital

Edegem, Antwerpen, 2650, Belgium

Location

Institut Jules Bordet

Anderlecht, Bruxelles-Capitale, Région de, 1070, Belgium

Location

UZ Leuven

Leuven, Vlaams-Brabant, 3000, Belgium

Location

Institut Curie

Paris, 75248, France

Location

Institut de cancérologie Strasbourg Europe (ICANS)

Strasbourg, 67033, France

Location

Hyogo Cancer Center

Akashi, Hyōgo, 673-8558, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Severance Hospital, Yonsei University Health System

Seoul, Korea, 03722, South Korea

Location

Seoul National University Hospital

Seoul, Seoul, Korea, 03080, South Korea

Location

Asan Medical Center

Seoul, Seoul-teukbyeolsi [Seoul], 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Clínic de Barcelona

Barcelona, Catalunya [Cataluña], 08036, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Madrid, Comunidad de, 28041, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, Valenciana, Comunitat, 46010, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañon

Madrid, 28009, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clinico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Fundación Instituto Valenciano de Oncología

Valencia, 46009, Spain

Location

Kaohsiung Medical University Hospital

Kaohsiung City, 80756, Taiwan

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

National Cheng-Kung Uni. Hosp.

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 10055, Taiwan

Location

Mackay Memorial Hospital

Taipei, 10449, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Related Publications (2)

• Bhave M, Jhaveri KL, Kaufman PA, Aftimos P, Lombard J, Giridhar KV, Im SA, Ma CX, Lee KT, Kim SB, Sohn J, Li Y, Yuen E, Estrem ST, Nguyen B, Makena MR, Ismail-Khan R, Beeram M. Imlunestrant, an oral selective estrogen receptor degrader, in combination with HER2 directed therapy, with or without abemaciclib, in ER-positive, HER2-positive advanced breast cancer: results from the phase 1a/1b EMBER study. Breast Cancer Res. 2025 Dec 21. doi: 10.1186/s13058-025-02168-6. Online ahead of print. No abstract available.

  PMID: 41423595 DERIVED

• Jhaveri KL, Lim E, Jeselsohn R, Ma CX, Hamilton EP, Osborne C, Bhave M, Kaufman PA, Beck JT, Manso Sanchez L, Parajuli R, Wang HC, Tao JJ, Im SA, Harnden K, Yonemori K, Dhakal A, Neven P, Aftimos P, Pierga JY, Lu YS, Larson T, Jerez Y, Sideras K, Sohn J, Kim SB, Saura C, Bardia A, Sammons SL, Bacchion F, Li Y, Yuen E, Estrem ST, Rodrik-Outmezguine V, Nguyen B, Ismail-Khan R, Smyth L, Beeram M. Imlunestrant, an Oral Selective Estrogen Receptor Degrader, as Monotherapy and in Combination With Targeted Therapy in Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Phase Ia/Ib EMBER Study. J Clin Oncol. 2024 Dec 10;42(35):4173-4186. doi: 10.1200/JCO.23.02733. Epub 2024 Sep 6.

  PMID: 39241211 DERIVED

Related Links

• A Study of LY3484356 in Participants With Advanced or Metastatic Breast Cancer

MeSH Terms

Conditions

Breast Neoplasms; Endometrial Neoplasms

Interventions

Imlunestrant; abemaciclib; Everolimus; Alpelisib; Trastuzumab; Aromatase Inhibitors; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Steroid Synthesis Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Estrogen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs

Study Officials

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2019
• First Posted: December 6, 2019
• Study Start: December 10, 2019
• Primary Completion: June 29, 2020
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 4, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

AU (5); TW (6); KR (4); ES (10); FR (2); BE (3); JP (2); US (42)