Recruiting
Phase 1
Phase 2

STX-478

Sponsor:

Eli Lilly and Company

Code:

NCT05768139

Conditions

Breast Cancer

Solid Tumors, Adult

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

STX-478

Fulvestrant

Ribociclib

Palbociclib

Letrozole

Study Details

Brief summary:

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, tamoxifen, 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.

Conditions

Breast Cancer

Solid Tumors, Adult

Study ID

NCT05768139

Start date

Apr 17, 2023

Status verified date

Jul, 2026

Completion date

Jul, 2030

Anticipated

Primary completion date

Jul, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key 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

Key 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

Study Design

Enrollment

880 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Dose Escalation (Advanced Solid Tumors)

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

experimental: Dose Expansion

  • Cohort A2: Gynecologic cancers
  • Cohort A3: Head and Neck Squamous Cell Carcinoma
  • Cohorts A4/A5: Other solid tumors not included in Cohorts A1, A2, A3 expressing PI3Kα mutations
  • Cohort A6: Endometrial cancer
  • Cohort A7: Non-gastrointestinal solid tumors

experimental: Dose Selection/Expansion: Combination STX-478 + fulvestrant

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

experimental: 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

experimental: Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant]

CDK4/6 inhibitor therapy in Cohort A8: all solid tumors Cohort B2 and Cohort F: HR+/HER2- or HR+/HER2 low breast cancer expressing PI3Kα mutations

Interventions

STX-478

STX-478 is a mutant-selective PI3Kα inhibitor

Fulvestrant

Fulvestrant

Ribociclib

Ribociclib

Palbociclib

Palbociclib

Letrozole

Letrozole

Anastrozole

Anastrozole

Exemestane

Exemestane

Tamoxifen

Tamoxifen

Abemaciclib

Abemaciclib

Imlunestrant

Imlunestrant

Metformin

Metformin

Primary outcome measure

  • Number of participants who experience at least 1 Dose Limiting Toxicity (DLT) [ Time Frame: First 28 days of treatment ]
  • Proportion of participants who experience at least 1 DLT during the first 28 days of treatment [ Time Frame: First 28 days of treatment ]
  • Objective response rate (ORR) defined as the percentage of participants with partial response or complete response based on RECIST 1.1 [ Time Frame: 12 months ]
  • Incidence of TEAEs/SAEs ≥ grade 2 [ Time Frame: 12 months ]
  • Frequency of TEAEs according to CTCAE v5.0 criteria [ Time Frame: 12 months ]

Central Contacts and Locations

Central contacts

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

1-317-615-4559LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

clinical_inquiry_hub@lilly.com

Locations

Ellison Clinic at Saint John's

Recruiting

Los Angeles, California, United States, 90064

Principal Investigator:

Reva Basho

UCSF Medical Center at Mission Bay

Recruiting

San Francisco, California, United States, 94143

Principal Investigator:

Varun Monga

University of Colorado Cancer Center

Recruiting

Aurora, Colorado, United States, 80045

Principal Investigator:

Anthony Elias

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Principal Investigator:

Aixa Soyano

Winship Cancer Institute, Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Principal Investigator:

Manali Bhave

University of Iowa

Recruiting

Iowa City, Iowa, United States, 52242

Principal Investigator:

Mark Burkard

Louisiana State University Health Sciences Center

Recruiting

New Orleans, Louisiana, United States, 70112

Principal Investigator:

Shou-Ching Tang

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02115

Principal Investigator:

Dejan Juric

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Principal Investigator:

Antonio Giordano

START Midwest

Recruiting

Grand Rapids, Michigan, United States, 49546

Principal Investigator:

Manish Sharma

Saint Luke's Cancer Institute

Recruiting

Kansas City, Missouri, United States, 64111-3220

Principal Investigator:

Timothy Pluard

Washington University

Recruiting

St Louis, Missouri, United States, 63110

Principal Investigator:

Cynthia Ma

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Principal Investigator:

Komal Jhaveri

UH Cleveland Medical Center

Recruiting

Cleveland, Ohio, United States, 44106

Principal Investigator:

Alberto Montero

Stefanie Spielman Comprehensive Breast Center

Recruiting

Columbus, Ohio, United States, 43212

Principal Investigator:

Robert Wesolowski

Providence Cancer Institute Franz Clinic

Recruiting

Portland, Oregon, United States, 97213

Principal Investigator:

David Page

The West Clinic, PLLC dba West Cancer Center

Recruiting

Germantown, Tennessee, United States, 38138

Principal Investigator:

Gregory Vidal

Sarah Cannon Research Institute

Recruiting

Nashville, Tennessee, United States, 37203

Principal Investigator:

SMO Sarah Cannon Research Inst.

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Recruiting

Dallas, Texas, United States, 75246-2092

Principal Investigator:

Joyce O'Shaughnessy

University of Texas Southwestern

Recruiting

Dallas, Texas, United States, 75390

Principal Investigator:

Nisha Unni

University of Texas MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Principal Investigator:

Jordi Rodon Ahnert

START San Antonio

Recruiting

San Antonio, Texas, United States, 78229

Principal Investigator:

Amita Patnaik

START Mountain Region

Recruiting

West Valley City, Utah, United States, 84119

Principal Investigator:

William McKean

USO-Virginia Cancer Specialists, PC

Recruiting

Fairfax, Virginia, United States, 22031

Principal Investigator:

Alexander Spira

More Information

Sponsor

Eli Lilly and Company

Last update posted

Jul 7, 2026

Last verified

Jul, 2026

Keywords

  • 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
  • Abemaciclib

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Eli Lilly and Company on 2026-07-07.