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NCT05768139PHASE1, PHASE2Recruiting

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

Eli Lilly and Company

Start Date

4/17/2023

Completion Date

7/1/2030

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

STX-478

DRUG

Fulvestrant

DRUG

Ribociclib

DRUG

Palbociclib

DRUG

Letrozole

DRUG

Anastrozole

DRUG

Exemestane

DRUG

Tamoxifen

DRUG

Abemaciclib

DRUG

Imlunestrant

DRUG

Metformin

Interested in This Trial?

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Conditions

Breast CancerSolid Tumors, Adult

Locations

Ellison Clinic at Saint John's

Los Angeles, California 90064

United States

UCSF Medical Center at Mission Bay

San Francisco, California 94143

United States

University of Colorado Cancer Center

Aurora, Colorado 80045

United States

Yale-New Haven Hospital

New Haven, Connecticut 06510

United States

Florida Cancer Specialists ORLANDO/DDU

Lake Mary, Florida 32746

United States

Moffitt Cancer Center

Tampa, Florida 33612

United States

Winship Cancer Institute, Emory University

Atlanta, Georgia 30322

United States

University of Iowa

Iowa City, Iowa 52242

United States

Louisiana State University Health Sciences Center

New Orleans, Louisiana 70112

United States

Massachusetts General Hospital

Boston, Massachusetts 02115

United States

Dana-Farber Cancer Institute

Boston, Massachusetts 02215

United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan 48201

United States

START Midwest

Grand Rapids, Michigan 49546

United States

Saint Luke's Cancer Institute

Kansas City, Missouri 64111-3220

United States

Washington University

St Louis, Missouri 63110

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

UH Cleveland Medical Center

Cleveland, Ohio 44106

United States

Stefanie Spielman Comprehensive Breast Center

Columbus, Ohio 43212

United States

Providence Cancer Institute Franz Clinic

Portland, Oregon 97213

United States

The West Clinic, PLLC dba West Cancer Center

Germantown, Tennessee 38138

United States

Sarah Cannon Research Institute

Nashville, Tennessee 37203

United States

Mary Crowley Cancer Research Center

Dallas, Texas 75230

United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas 75246-2092

United States

University of Texas Southwestern

Dallas, Texas 75390

United States

University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

START San Antonio

San Antonio, Texas 78229

United States

START Mountain Region

West Valley City, Utah 84119

United States

USO-Virginia Cancer Specialists, PC

Fairfax, Virginia 22031

United States

Institut Jules Bordet

Anderlecht, 1070

Belgium

UZ Leuven

Leuven, 3000

Belgium

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

Bordeaux, 33000

France

Centre Leon Berard

Lyon, 69008

France

Institut Paoli-Calmettes

Marseille, 13009

France

Centre Antoine-Lacassagne

Nice, 06189

France

Institut Claudius Regaud

Toulouse, 31059

France

Gustave Roussy

Villejuif, 94805

France

Universitätsklinikum Erlangen

Erlangen, 91054

Germany

Mater Misericordiae Hospital

Dublin,

Ireland

Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo

Alessandria, 15100

Italy

Spedali Civili di Brescia

Brescia, 25123

Italy

Istituto Nazionale per lo Studio e la Cura dei Tumori

Milan, 20133

Italy

Istituto Europeo di Oncologia

Milan, 20141

Italy

Fondazione IRCCS San Gerardo dei Tintori

Monza, 20900

Italy

Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa Chiara

Pisa, 56126

Italy

Ospedale Santa Maria delle Croci

Ravenna, 48121

Italy

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 168

Italy

Centro Ricerche Cliniche di Verona s.r.l.

Verona, 37134

Italy

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395

Japan

Kansai Medical University Hospital

Hirakata, 573-1191

Japan

The Cancer Institute Hospital of JFCR

Kōtō City, 135-8550

Japan

Kyoto University Hospital

Kyoto, 606-8507

Japan

Netherlands Cancer Institute

Amsterdam, 1066CX

Netherlands

Erasmus MC

Rotterdam, 3015GD

Netherlands

Hospital Quiron Barcelona

Barcelona, 08023

Spain

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

Barcelona, 08023

Spain

Instituto Oncologico Dr Rosell (IOR)

Barcelona, 08028

Spain

Hospital Universitari Vall d'Hebron

Barcelona, 08035

Spain

Hospital San Pedro

Logroño, 26006

Spain

MD Anderson Cancer Center

Madrid, 28033

Spain

Hospital Clinico San Carlos

Madrid, 28040

Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040

Spain

Hospital Universitario HM Sanchinarro

Madrid, 28050

Spain

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, 28223

Spain

Hospital Universitari Sant Joan de Reus

Reus, 43204

Spain

Hospital Universitario Virgen Macarena

Seville, 41009

Spain