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

NCT05768139 | Recruiting Phase 1 FDA Drug

• 5 other identifiers: 276912023-504807-94-002023-000442-41J6M-OX-JSGASTX-478-101
• Study Type: interventional
• Target: 880
• Locations: 9 countries
• Sites: 66

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

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

Outcome Measures

Primary Outcomes (5)

• Number of participants who experience at least 1 Dose Limiting Toxicity (DLT)

  First 28 days of treatment

• Proportion of participants who experience at least 1 DLT during the first 28 days of treatment

  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

  12 months

• Incidence of TEAEs/SAEs ≥ grade 2

  12 months

• Frequency of TEAEs according to CTCAE v5.0 criteria

  12 months

Secondary Outcomes (10)

• Cmax of STX-478

  12 months

• AUC(0-inf) of STX-478

  12 months

• AUC(0-t) of STX-478

  12 months

• AUC(0-τ) of STX-478

  12 months

• Change from baseline in ctDNA levels

  12 months

Study Arms (5)

Dose Escalation (Advanced Solid Tumors)

EXPERIMENTAL

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

Drug: STX-478

Dose Expansion

EXPERIMENTAL

* 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

Drug: STX-478

Dose Selection/Expansion: Combination STX-478 + fulvestrant

EXPERIMENTAL

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

Drug: STX-478; Drug: Fulvestrant

Dose Selection/Expansion Combination

EXPERIMENTAL

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

Drug: STX-478; Drug: Fulvestrant; Drug: Ribociclib; Drug: Palbociclib; Drug: Letrozole; Drug: Anastrozole; Drug: Exemestane; Drug: Tamoxifen; Drug: Abemaciclib; Drug: Imlunestrant

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

EXPERIMENTAL

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

Drug: STX-478; Drug: Fulvestrant; Drug: Ribociclib; Drug: Palbociclib; Drug: Letrozole; Drug: Anastrozole; Drug: Exemestane; Drug: Abemaciclib; Drug: Metformin

Interventions

STX-478 DRUG

STX-478 is a mutant-selective PI3Kα inhibitor

Also known as: LY4064809, Tersolisib

Dose Escalation (Advanced Solid Tumors); Dose Expansion; Dose Selection/Expansion Combination; Dose Selection/Expansion: Combination STX-478 + fulvestrant; Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant]

Fulvestrant DRUG

Fulvestrant

Also known as: Faslodex

Dose Selection/Expansion Combination; Dose Selection/Expansion: Combination STX-478 + fulvestrant; Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant]

Ribociclib DRUG

Ribociclib

Also known as: Kisqali

Dose Selection/Expansion Combination; Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant]

Palbociclib DRUG

Palbociclib

Also known as: Ibrance

Dose Selection/Expansion Combination; Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant]

Letrozole DRUG

Letrozole

Also known as: Femara

Dose Selection/Expansion Combination; Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant]

Anastrozole DRUG

Anastrozole

Also known as: Arimidex

Dose Selection/Expansion Combination; Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant]

Exemestane DRUG

Exemestane

Also known as: Aromasin

Dose Selection/Expansion Combination; Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant]

Tamoxifen DRUG

Tamoxifen

Also known as: Nolvadex, Soltamox

Dose Selection/Expansion Combination

Abemaciclib DRUG

Abemaciclib

Also known as: Verzenio

Dose Selection/Expansion Combination; Experimental: Drug to Drug Interaction (DDI) Metformin STX-478 +/- ET ([AIs or fulvestrant]

Imlunestrant DRUG

Imlunestrant

Also known as: Inluriyo

Dose Selection/Expansion Combination

Metformin DRUG

Metformin

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

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (66)

Ellison Clinic at Saint John's

Los Angeles, California, 90064, United States

RECRUITING

UCSF Medical Center at Mission Bay

San Francisco, California, 94143, United States

RECRUITING

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

RECRUITING

Yale-New Haven Hospital

New Haven, Connecticut, 06510, United States

COMPLETED

Florida Cancer Specialists ORLANDO/DDU

Lake Mary, Florida, 32746, United States

COMPLETED

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

University of Iowa

Iowa City, Iowa, 52242, United States

RECRUITING

Louisiana State University Health Sciences Center

New Orleans, Louisiana, 70112, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

TERMINATED

START Midwest

Grand Rapids, Michigan, 49546, United States

RECRUITING

Saint Luke's Cancer Institute

Kansas City, Missouri, 64111-3220, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

UH Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

Stefanie Spielman Comprehensive Breast Center

Columbus, Ohio, 43212, United States

RECRUITING

Providence Cancer Institute Franz Clinic

Portland, Oregon, 97213, United States

RECRUITING

The West Clinic, PLLC dba West Cancer Center

Germantown, Tennessee, 38138, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

COMPLETED

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246-2092, United States

RECRUITING

University of Texas Southwestern

Dallas, Texas, 75390, United States

NOT YET RECRUITING

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

START San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

START Mountain Region

West Valley City, Utah, 84119, United States

RECRUITING

USO-Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

RECRUITING

Institut Jules Bordet

Anderlecht, 1070, Belgium

NOT YET RECRUITING

UZ Leuven

Leuven, 3000, Belgium

NOT YET RECRUITING

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

Bordeaux, 33000, France

RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

Institut Paoli-Calmettes

Marseille, 13009, France

NOT YET RECRUITING

Centre Antoine-Lacassagne

Nice, 06189, France

NOT YET RECRUITING

Institut Claudius Regaud

Toulouse, 31059, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Universitätsklinikum Erlangen

Erlangen, 91054, Germany

NOT YET RECRUITING

Universitätsmedizin Mannheim

Mannheim, 68167, Germany

NOT YET RECRUITING

Mater Misericordiae Hospital

Dublin, Ireland

RECRUITING

Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo

Alessandria, 15100, Italy

NOT YET RECRUITING

Spedali Civili di Brescia

Brescia, 25123, Italy

NOT YET RECRUITING

Istituto Nazionale per lo Studio e la Cura dei Tumori

Milan, 20133, Italy

RECRUITING

Istituto Europeo di Oncologia

Milan, 20141, Italy

RECRUITING

Fondazione IRCCS San Gerardo dei Tintori

Monza, 20900, Italy

RECRUITING

Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa Chiara

Pisa, 56126, Italy

RECRUITING

Ospedale Santa Maria delle Croci

Ravenna, 48121, Italy

NOT YET RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli

Roma, 168, Italy

RECRUITING

Centro Ricerche Cliniche di Verona s.r.l.

Verona, 37134, Italy

RECRUITING

National Hospital Organization Kyushu Cancer Center

Fukuoka, 811-1395, Japan

RECRUITING

Kansai Medical University Hospital

Hirakata, 573-1191, Japan

RECRUITING

The Cancer Institute Hospital of JFCR

Kōtō City, 135-8550, Japan

RECRUITING

Kyoto University Hospital

Kyoto, 606-8507, Japan

RECRUITING

Netherlands Cancer Institute

Amsterdam, 1066CX, Netherlands

RECRUITING

Erasmus MC

Rotterdam, 3015GD, Netherlands

RECRUITING

Hospital Quiron Barcelona

Barcelona, 08023, Spain

RECRUITING

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

Barcelona, 08023, Spain

RECRUITING

Instituto Oncologico Dr Rosell (IOR)

Barcelona, 08028, Spain

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital San Pedro

Logroño, 26006, Spain

RECRUITING

MD Anderson Cancer Center

Madrid, 28033, Spain

RECRUITING

Hospital Clinico San Carlos

Madrid, 28040, Spain

RECRUITING

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

RECRUITING

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

RECRUITING

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, 28223, Spain

RECRUITING

Hospital Universitari Sant Joan de Reus

Reus, 43204, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Endometrial Neoplasms; Ovarian Neoplasms; Uterine Cervical Neoplasms; Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck; Hereditary Sensory and Autonomic Neuropathies

Interventions

STX-478; Fulvestrant; ribociclib; palbociclib; Letrozole; Anastrozole; exemestane; Tamoxifen; abemaciclib; Imlunestrant; Metformin

Condition Hierarchy (Ancestors)

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; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Cervical Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Biguanides; Guanidines; Amidines

Study Officials

• 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)

  Eli Lilly and Company

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

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

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: In Part 1, Part 2 B0, B2, and B3, and Part 3 C0, D0, E0, F and A8, participants are assigned to intervention. In Part 2 B1 and Part 3 C1, D1, and E1, participants are randomized to doses
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2023
• First Posted: March 14, 2023
• Study Start: April 17, 2023
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2030
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); FR (6); JP (4); ES (12); NL (2); US (28); BE (2); IT (9); IE (1)