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Breast CancerPhase 1/2PIKALO-1NCT05768139

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

A Phase 1/2 study testing STX-478, Fulvestrant and Ribociclib in people with Breast Cancer and Solid Tumors, Adult, run by Eli Lilly and Company at 65 sites in 9 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer, Solid Tumors, Adult
What is being tested?
STX-478, Fulvestrant and Ribociclib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
880 participants
Where
65 sitesin 9 countries
Study dates
17 Apr 2023to Jul 2030
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

65 sites in 9 countries. Contact the study team or a site near you to ask about taking part.

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

65 sites in 9 countries

United States28 sites, 24 recruiting

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia, 30322

    Manali Bhave

    Recruiting

  • University of Colorado Cancer Center

    Aurora, Colorado, 80045

    Anthony Elias

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02115

    Dejan Juric

    Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Antonio Giordano

    Recruiting

  • UH Cleveland Medical Center

    Cleveland, Ohio, 44106

    Alberto Montero

    Recruiting

  • Stefanie Spielman Comprehensive Breast Center

    Columbus, Ohio, 43212

    Robert Wesolowski

    Recruiting

  • Mary Crowley Cancer Research Center

    Dallas, Texas, 75230

    Completed

  • Texas Oncology-Baylor Charles A. Sammons Cancer Center

    Dallas, Texas, 75246-2092

    Joyce O'Shaughnessy

    Recruiting

  • University of Texas Southwestern

    Dallas, Texas, 75390

    Nisha Unni

    Recruiting

  • Barbara Ann Karmanos Cancer Institute

    Detroit, Michigan, 48201

    Terminated

  • USO-Virginia Cancer Specialists, PC

    Fairfax, Virginia, 22031

    Alexander Spira

    Recruiting

  • The West Clinic, PLLC dba West Cancer Center

    Germantown, Tennessee, 38138

    Gregory Vidal

    Recruiting

  • START Midwest

    Grand Rapids, Michigan, 49546

    Manish Sharma

    Recruiting

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Jordi Rodon Ahnert

    Recruiting

  • University of Iowa

    Iowa City, Iowa, 52242

    Mark Burkard

    Recruiting

  • Saint Luke's Cancer Institute

    Kansas City, Missouri, 64111-3220

    Timothy Pluard

    Recruiting

  • Florida Cancer Specialists ORLANDO/DDU

    Lake Mary, Florida, 32746

    Completed

  • Ellison Clinic at Saint John's

    Los Angeles, California, 90064

    Reva Basho

    Recruiting

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

    SMO Sarah Cannon Research Inst.

    Recruiting

  • Yale-New Haven Hospital

    New Haven, Connecticut, 06510

    Completed

  • Louisiana State University Health Sciences Center

    New Orleans, Louisiana, 70112

    Shou-Ching Tang

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Komal Jhaveri

    Recruiting

  • Providence Cancer Institute Franz Clinic

    Portland, Oregon, 97213

    David Page

    Recruiting

  • START San Antonio

    San Antonio, Texas, 78229

    Amita Patnaik

    Recruiting

  • UCSF Medical Center at Mission Bay

    San Francisco, California, 94143

    Varun Monga

    Recruiting

  • Washington University

    St Louis, Missouri, 63110

    Cynthia Ma

    Recruiting

  • Moffitt Cancer Center

    Tampa, Florida, 33612

    Aixa Soyano

    Recruiting

  • START Mountain Region

    West Valley City, Utah, 84119

    William McKean

    Recruiting

Other trials in United States

Spain12 sites, 12 recruiting

  • Hospital Quiron Barcelona

    Barcelona, 08023

    Guzman Alonso Casal

    Recruiting

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

    Barcelona, 08023

    Tatiana Hernandez Guerrero

    Recruiting

  • Instituto Oncologico Dr Rosell (IOR)

    Barcelona, 08028

    Jose Manuel Perez Garcia

    Recruiting

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

    Cristina Saura Manich

    Recruiting

  • Hospital San Pedro

    Logroño, 26006

    Maria Jose de Miguel Luken

    Recruiting

  • MD Anderson Cancer Center

    Madrid, 28033

    Maria Calvo Plaza

    Recruiting

  • Hospital Clinico San Carlos

    Madrid, 28040

    Jorge Bartolome Arcilla

    Recruiting

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

    Bernard Doger de Speville Uribe

    Recruiting

  • Hospital Universitario HM Sanchinarro

    Madrid, 28050

    Juan Jose Soto

    Recruiting

  • Hospital Universitario Quironsalud Madrid

    Pozuelo de Alarcón, 28223

    Valentina Boni

    Recruiting

  • Hospital Universitari Sant Joan de Reus

    Reus, 43204

    Kepa Amillano Parraga

    Recruiting

  • Hospital Universitario Virgen Macarena

    Seville, 41009

    Luis de la Cruz Merino

    Recruiting

Other trials in Spain

Italy9 sites, 9 recruiting

  • Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo

    Alessandria, 15100

    Giulia Gallizzi

    Recruiting

  • Spedali Civili di Brescia

    Brescia, 25123

    Rebecca Pedersini

    Not yet recruiting

  • Istituto Nazionale per lo Studio e la Cura dei Tumori

    Milan, 20133

    Giulia Bianchi

    Recruiting

  • Istituto Europeo di Oncologia

    Milan, 20141

    Giuseppe Curigliano

    Recruiting

  • Fondazione IRCCS San Gerardo dei Tintori

    Monza, 20900

    Marina Cazzaniga

    Recruiting

  • Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa Chiara

    Pisa, 56126

    Carmelo Bengala

    Recruiting

  • Ospedale Santa Maria delle Croci

    Ravenna, 48121

    Stefano Tamberi

    Recruiting

  • Fondazione Policlinico Universitario Agostino Gemelli

    Roma, 168

    Gennaro Daniele

    Recruiting

  • Centro Ricerche Cliniche di Verona s.r.l.

    Verona, 37134

    Andrea Zivi

    Recruiting

Other trials in Italy

France6 sites, 6 recruiting

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

    Bordeaux, 33000

    Maxime Brunet

    Recruiting

  • Centre Leon Berard

    Lyon, 69008

    Isabelle Ray-Coquard

    Recruiting

  • Institut Paoli-Calmettes

    Marseille, 13009

    Cecile Vicier

    Recruiting

  • Centre Antoine-Lacassagne

    Nice, 06189

    Philippe Follana

    Recruiting

  • Institut Claudius Regaud

    Toulouse, 31059

    Eleonora De Maio

    Recruiting

  • Gustave Roussy

    Villejuif, 94805

    Barbara Pistilli

    Recruiting

Other trials in France

Japan4 sites, 4 recruiting

  • National Hospital Organization Kyushu Cancer Center

    Fukuoka, 811-1395

    81120023812

    Eriko Tokunaga

    Recruiting

  • Kansai Medical University Hospital

    Hirakata, 573-1191

    81120023812

    Toshio Shimizu

    Recruiting

  • The Cancer Institute Hospital of JFCR

    Kōtō City, 135-8550

    81120023812

    Yukinori Ozaki

    Recruiting

  • Kyoto University Hospital

    Kyoto, 606-8507

    81120023812

    TAKAKO NAKAJIMA

    Recruiting

Other trials in Japan

Belgium2 sites, 2 recruiting

  • Institut Jules Bordet

    Anderlecht, 1070

    Philippe Aftimos

    Recruiting

  • UZ Leuven

    Leuven, 3000

    Patrick Neven

    Recruiting

Other trials in Belgium

Netherlands2 sites, 2 recruiting

  • Netherlands Cancer Institute

    Amsterdam, 1066CX

    Marloes G.J. van Dongen

    Recruiting

  • Erasmus MC

    Rotterdam, 3015GD

    Agnes Jager

    Recruiting

Other trials in Netherlands

Germany1 site, 1 recruiting

  • Universitätsklinikum Erlangen

    Erlangen, 91054

    Peter Fasching

    Not yet recruiting

Other trials in Germany

Ireland1 site, 1 recruiting

  • Mater Misericordiae Hospital

    Dublin

    Austin Duffy

    Recruiting

Other trials in Ireland

About this study

Official title: First-in-Human Study of STX-478, a Mutant-Selective PI3Kα Inhibitor as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors

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.

Being tested
STX-478, Fulvestrant, Ribociclib, Palbociclib, Letrozole
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
Medical subject headings
Breast Neoplasms, Neoplasms by Site, Neoplasms, Breast Diseases, Endometrial Neoplasms, Ovarian Neoplasms, Uterine Cervical Neoplasms, Head and Neck Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • STX-478Drug

    Also called LY4064809, Tersolisib

    STX-478 is a mutant-selective PI3Kα inhibitor

  • FulvestrantDrug

    Also called Faslodex

    Fulvestrant

  • RibociclibDrug

    Also called Kisqali

    Ribociclib

  • PalbociclibDrug

    Also called Ibrance

    Palbociclib

  • LetrozoleDrug

    Also called Femara

    Letrozole

  • AnastrozoleDrug

    Also called Arimidex

    Anastrozole

  • ExemestaneDrug

    Also called Aromasin

    Exemestane

  • TamoxifenDrug

    Also called Nolvadex, Soltamox

    Tamoxifen

  • AbemaciclibDrug

    Also called Verzenio

    Abemaciclib

  • ImlunestrantDrug

    Also called Inluriyo

    Imlunestrant

  • MetforminDrug

    Metformin

Study groups in NCT05768139
Study groupRoleWhat they receive
Dose Escalation (Advanced Solid Tumors)Experimental* Cohort A0: Advanced Solid tumors expressing PI3Kα mutations * Cohort A1: HR+ breast cancer expressing PI3Kα mutations
Receives: Drug: STX-478
Dose ExpansionExperimental* 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
Receives: Drug: STX-478
Dose Selection/Expansion: Combination STX-478 + fulvestrantExperimentalCohort B: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Kα mutations
Receives: Drug: STX-478; Drug: Fulvestrant
Dose Selection/Expansion CombinationExperimentalSTX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations
Receives: 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]ExperimentalCDK4/6 inhibitor therapy in Cohort A8: all solid tumors Cohort B2 and Cohort F: HR+/HER2- or HR+/HER2 low breast cancer expressing PI3Kα mutations
Receives: Drug: STX-478; Drug: Fulvestrant; Drug: Ribociclib; Drug: Palbociclib; Drug: Letrozole; Drug: Anastrozole; Drug: Exemestane; Drug: Abemaciclib; Drug: Metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: First 28 days of treatment

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

    Measured: First 28 days of treatment

  3. Objective response rate (ORR) defined as the percentage of participants with partial response or complete response based on RECIST 1.1

    Measured: 12 months

  4. Incidence of TEAEs/SAEs ≥ grade 2

    Measured: 12 months

  5. Frequency of TEAEs according to CTCAE v5.0 criteria

    Measured: 12 months

Secondary outcomes (10)

  1. Cmax of STX-478

    Measured: 12 months

  2. AUC(0-inf) of STX-478

    Measured: 12 months

  3. AUC(0-t) of STX-478

    Measured: 12 months

  4. AUC(0-τ) of STX-478

    Measured: 12 months

  5. Change from baseline in ctDNA levels

    Measured: 12 months

  6. Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin (HbA1c)

    Measured: 12 months

  7. Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose

    Measured: 12 months

  8. Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide

    Measured: 12 months

  9. Change in ECOG performance status

    Measured: 12 months

  10. Disease Control Rate (DCR) per RECIST v1.1, measured as percentage of participants with Complete Response

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2023
  2. Study start17 Apr 2023
  3. Primary completionJul 2030 (estimated)
  4. Study completionJul 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
880 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05768139
Sponsor's protocol ID
27691
Other IDs
2023-504807-94-00, 2023-000442-41, J6M-OX-JSGA, STX-478-101, 2023
Acronym
PIKALO-1
Status last verified
Jul 2026
First submitted
1 Mar 2023
Last updated
7 Jul 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing STX-478, Fulvestrant and Ribociclib in people with Breast Cancer and Solid Tumors, Adult, run by Eli Lilly and Company at 65 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 65 sites in United States, Spain, Italy, France, Japan and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or (1-317-615-4559, LillyTrials@Lilly.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants who experience at least 1 Dose Limiting Toxicity (DLT) (time frame: First 28 days of treatment). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05768139.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.

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