First-in-Human Study of STX-478 as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors

NCT ID: NCT05768139

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

720 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-04-17

Study Completion Date

2030-07-31

Brief Summary

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Study STX-478-101 (LY4064809) is a multipart, open-label, phase 1/2 study evaluating the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of STX-478 (LY4064809) in participants with advanced solid tumors with P13Ka mutations.

Part 1 will evaluate STX-478 as monotherapy in participants with advanced solid tumors. Part 2 will evaluate STX-478 therapy as combination therapy with fulvestrant in participants with hormone receptor positive (HR+) breast cancer. Part 3 will evaluate STX-478 as combination therapy with endocrine therapy (aromatase inhibitors, fulvestrant or imlunestrant) and a CDK4/6 Inhibitor (either Ribociclib, Palbociclib or Abemaciclib) in participants with HR+ breast cancer.

Each study part will include a 28-day screening period, followed by treatment with STX-478 monotherapy or combination therapy.

Detailed Description

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Conditions

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Breast Cancer Solid Tumors, Adult

Keywords

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Breast Neoplasms Neoplasms by Site Neoplasms Breast Diseases HER2-negative breast cancer HR-positive breast cancer Gynecologic cancer Endometrial cancer Ovarian cancer Cervical cancer Head and neck cancer Head and neck squamous cell carcinoma Fulvestrant Antineoplastic Agents PI3Kα PI3K alpha PI3Kα mutation Alpelisib STX-478 PI3Kα inhibitor Estrogen Receptor Antagonists Estrogen Antagonists Hormone Receptor Antagonists Hormone Antagonists Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs Palbociclib Ribociclib PIK3CA PIK3CA mutation Aromatase inhibitor Letrozole Anastrozole Exemestane Imlunestrant Inavolisib Capivasertib

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

In Part 1, Part 2 B0 and B2, and Part 3 C0, D0, and E0, participants are assigned to intervention. In Part 2 B1 and Part 3 C1, D1, and E1, participants are randomized to doses

Study Groups

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Dose Escalation (Advanced Solid Tumors)

* Cohort A0: Advanced Solid tumors expressing PI3Kα mutations
* Cohort A1: HR+ breast cancer expressing PI3Kα mutations

Group Type EXPERIMENTAL

STX-478

Intervention Type DRUG

STX-478 is a mutant-selective PI3Kα inhibitor

Dose Expansion

* Cohort A1: HR+/HER2- breast cancer expressing PI3Ka mutations
* Cohort A2: Gynecologic cancers
* Cohort A3: Head and Neck Squamous Cell Carcinoma
* Cohorts A4/A5: Other solid tumors not included in Cohorts A1, A2, or A3 expressing PI3Kα mutations
* Cohort A6: Endometrial cancer

Group Type EXPERIMENTAL

STX-478

Intervention Type DRUG

STX-478 is a mutant-selective PI3Kα inhibitor

Dose Selection/Expansion: Combination STX-478 + fulvestrant

Cohort B: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Kα mutations

Group Type EXPERIMENTAL

STX-478

Intervention Type DRUG

STX-478 is a mutant-selective PI3Kα inhibitor

Fulvestrant

Intervention Type DRUG

Fulvestrant

Dose Selection/Expansion Combination

STX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations

Group Type EXPERIMENTAL

STX-478

Intervention Type DRUG

STX-478 is a mutant-selective PI3Kα inhibitor

Fulvestrant

Intervention Type DRUG

Fulvestrant

Ribociclib

Intervention Type DRUG

Ribociclib

Palbociclib

Intervention Type DRUG

Palbociclib

Letrozole

Intervention Type DRUG

Letrozole

Anastrozole

Intervention Type DRUG

Anastrozole

Exemestane

Intervention Type DRUG

Exemestane

Interventions

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STX-478

STX-478 is a mutant-selective PI3Kα inhibitor

Intervention Type DRUG

Fulvestrant

Fulvestrant

Intervention Type DRUG

Ribociclib

Ribociclib

Intervention Type DRUG

Palbociclib

Palbociclib

Intervention Type DRUG

Letrozole

Letrozole

Intervention Type DRUG

Anastrozole

Anastrozole

Intervention Type DRUG

Exemestane

Exemestane

Intervention Type DRUG

Other Intervention Names

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LY4064809 Faslodex Kisqali Ibrance Femara Arimidex Aromasin

Eligibility Criteria

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Inclusion Criteria

* Has an advanced or refractory solid tumor malignancy that is metastatic or locally advanced and unresectable (as specified by Cohort)
* Has a new or recent tumor biopsy (collected at screening, if feasible) or will provide an adequate tissue sample prior to screening
* Has a tumor that harbors a documented PI3Kα mutation (cohort specific criterion for cohort-specific mutation types)
* Is ≥18 years of age at the time of signing the ICF
* Has an ECOG performance status score of 0 or 1 at screening
* Has adequate organ function as defined per protocol

Exclusion Criteria

* Has history (within ≤2 years before screening) of a solid tumor or hematological malignancy that is histologically distinct from the cancers being studied
* Has symptomatic brain or spinal metastases
* Has an established diagnosis of uncontrolled diabetes mellitus (defined as HbA1c ≥8% and/or FBG ≥140 mg/dL \[7.7 mmol/L\] and/or requiring or required insulin).
* Has had prior treatment with PI3K/AKT/mTOR inhibitor(s), except in certain circumstances
* Has had treatment with any local or systemic antineoplastic therapy or investigational anticancer agent within 14 days or 4 half-lives, whichever is longer, prior to the initiation of study treatment up to a maximum washout period of 28 days. Endocrine therapy does not require a washout period if the patient is enrolling in a cohort with the same combination endocrine therapy.
* Has toxicities from previous anticancer therapies that have not resolved to baseline levels or CTCAE grade ≤1, with the exception of alopecia and peripheral neuropathy.
* Has had radiotherapy within 14 days before the initiation of study treatment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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Ellison Clinic at Saint John's

Los Angeles, California, United States

Site Status NOT_YET_RECRUITING

UCSF Medical Center at Mission Bay

San Francisco, California, United States

Site Status RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, United States

Site Status RECRUITING

Yale-New Haven Hospital

New Haven, Connecticut, United States

Site Status COMPLETED

Florida Cancer Specialists ORLANDO/DDU

Lake Mary, Florida, United States

Site Status RECRUITING

Moffitt Cancer Center

Tampa, Florida, United States

Site Status RECRUITING

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Site Status NOT_YET_RECRUITING

University of Iowa

Iowa City, Iowa, United States

Site Status RECRUITING

Louisiana State University Health Sciences Center

New Orleans, Louisiana, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status RECRUITING

START Midwest

Grand Rapids, Michigan, United States

Site Status RECRUITING

Saint Luke's Cancer Institute

Kansas City, Missouri, United States

Site Status RECRUITING

Washington University

St Louis, Missouri, United States

Site Status NOT_YET_RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

UH Cleveland Medical Center

Cleveland, Ohio, United States

Site Status RECRUITING

Stefanie Spielman Comprehensive Breast Center

Columbus, Ohio, United States

Site Status RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

Providence Cancer Institute Franz Clinic

Portland, Oregon, United States

Site Status RECRUITING

The West Clinic, PLLC dba West Cancer Center

Germantown, Tennessee, United States

Site Status RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Site Status RECRUITING

Mary Crowley Cancer Research Center

Dallas, Texas, United States

Site Status COMPLETED

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, United States

Site Status RECRUITING

University of Texas Southwestern

Dallas, Texas, United States

Site Status NOT_YET_RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

START San Antonio

San Antonio, Texas, United States

Site Status RECRUITING

START Mountain Region

West Valley City, Utah, United States

Site Status RECRUITING

University of Vermont Medical Center

Burlington, Vermont, United States

Site Status NOT_YET_RECRUITING

USO-Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status RECRUITING

Institut Jules Bordet

Anderlecht, , Belgium

Site Status NOT_YET_RECRUITING

UZ Leuven

Leuven, , Belgium

Site Status NOT_YET_RECRUITING

Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest

Bordeaux, , France

Site Status RECRUITING

Centre Leon Berard

Lyon, , France

Site Status RECRUITING

Institut Paoli-Calmettes

Marseille, , France

Site Status NOT_YET_RECRUITING

Centre Antoine-Lacassagne

Nice, , France

Site Status NOT_YET_RECRUITING

Institut Claudius Regaud

Toulouse, , France

Site Status RECRUITING

Gustave Roussy

Villejuif, , France

Site Status RECRUITING

Universitätsklinikum Erlangen

Erlangen, , Germany

Site Status NOT_YET_RECRUITING

Universitätsmedizin Mannheim

Mannheim, , Germany

Site Status NOT_YET_RECRUITING

Mater Misericordiae Hospital

Dublin, , Ireland

Site Status RECRUITING

Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

Site Status NOT_YET_RECRUITING

Spedali Civili di Brescia

Brescia, , Italy

Site Status NOT_YET_RECRUITING

Istituto Nazionale per lo Studio e la Cura dei Tumori

Milan, , Italy

Site Status RECRUITING

Istituto Europeo di Oncologia

Milan, , Italy

Site Status RECRUITING

Fondazione IRCCS San Gerardo dei Tintori

Monza, , Italy

Site Status RECRUITING

Ospedale Santa Maria delle Croci

Ravenna, , Italy

Site Status NOT_YET_RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli

Roma, , Italy

Site Status RECRUITING

Centro Ricerche Cliniche di Verona s.r.l.

Verona, , Italy

Site Status NOT_YET_RECRUITING

National Hospital Organization Kyushu Cancer Center

Fukuoka, , Japan

Site Status RECRUITING

Kansai Medical University Hospital

Hirakata, , Japan

Site Status RECRUITING

The Cancer Institute Hospital of JFCR

Kōtō City, , Japan

Site Status RECRUITING

Kyoto University Hospital

Kyoto, , Japan

Site Status RECRUITING

Netherlands Cancer Institute

Amsterdam, , Netherlands

Site Status RECRUITING

Erasmus MC

Rotterdam, , Netherlands

Site Status RECRUITING

Hospital Quiron Barcelona

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

South Texas Accelerated Research Therapeutics (START) Barcelona- HM Nou Delfos

Barcelona, , Spain

Site Status RECRUITING

Instituto Oncologico Dr Rosell (IOR)

Barcelona, , Spain

Site Status NOT_YET_RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Hospital San Pedro

Logroño, , Spain

Site Status RECRUITING

MD Anderson Cancer Center

Madrid, , Spain

Site Status RECRUITING

Hospital Clinico San Carlos

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario HM Sanchinarro

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, , Spain

Site Status RECRUITING

Hospital Universitari Sant Joan de Reus

Reus, , Spain

Site Status NOT_YET_RECRUITING

Hospital Universitario Virgen Macarena

Seville, , Spain

Site Status NOT_YET_RECRUITING

Countries

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United States Belgium France Germany Ireland Italy Japan Netherlands Spain

Central Contacts

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Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

Role: CONTACT

Phone: 1-317-615-4559

Email: [email protected]

Physicians interested in becoming principal investigators please contact

Role: CONTACT

Email: [email protected]

Facility Contacts

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Role: primary

Role: primary

Role: primary

Role: primary

Other Identifiers

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J6M-OX-JSGA

Identifier Type: OTHER

Identifier Source: secondary_id

STX-478-101

Identifier Type: OTHER

Identifier Source: secondary_id

2023-000442-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-504807-94-00

Identifier Type: CTIS

Identifier Source: secondary_id

27691

Identifier Type: -

Identifier Source: org_study_id