First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors (PIKALO-1)

July 3, 2026 updated by: Eli Lilly and Company

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

880

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
  • Phone Number: 1-317-615-4559
  • Email: LillyTrials@Lilly.com

Study Contact Backup

Study Locations

  • Belgium
      • Anderlecht, Belgium, 1070
        • Recruiting
        • Institut Jules Bordet
        • Principal Investigator:
          • Philippe Aftimos
      • Leuven, Belgium, 3000
        • Recruiting
        • UZ Leuven
        • Principal Investigator:
          • Patrick Neven
  • France
      • Bordeaux, France, 33000
        • Recruiting
        • Institut Bergonie - Centre Regional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
        • Principal Investigator:
          • Maxime Brunet
      • Lyon, France, 69008
        • Recruiting
        • Centre Léon Bérard
        • Principal Investigator:
          • Isabelle Ray-Coquard
      • Marseille, France, 13009
        • Recruiting
        • Institut Paoli-Calmettes
        • Principal Investigator:
          • Cecile Vicier
      • Nice, France, 06189
        • Recruiting
        • Centre Antoine-Lacassagne
        • Principal Investigator:
          • Philippe Follana
      • Toulouse, France, 31059
        • Recruiting
        • Institut Claudius Regaud
        • Principal Investigator:
          • Eleonora De Maio
      • Villejuif, France, 94805
        • Recruiting
        • Gustave Roussy
        • Principal Investigator:
          • Barbara Pistilli
  • Germany
      • Erlangen, Germany, 91054
        • Not yet recruiting
        • Universitätsklinikum Erlangen
        • Principal Investigator:
          • Peter Fasching
  • Ireland
      • Dublin, Ireland
        • Recruiting
        • Mater Misericordiae Hospital
        • Principal Investigator:
          • Austin Duffy
  • Italy
      • Alessandria, Italy, 15100
        • Recruiting
        • Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo
        • Principal Investigator:
          • Giulia Gallizzi
      • Brescia, Italy, 25123
        • Not yet recruiting
        • Spedali Civili di Brescia
        • Principal Investigator:
          • Rebecca Pedersini
      • Milan, Italy, 20141
        • Recruiting
        • Istituto Europeo di Oncologia
        • Principal Investigator:
          • Giuseppe Curigliano
      • Milan, Italy, 20133
        • Recruiting
        • Istituto Nazionale per lo Studio e la Cura dei Tumori
        • Principal Investigator:
          • Giulia Bianchi
      • Monza, Italy, 20900
        • Recruiting
        • Fondazione IRCCS San Gerardo dei Tintori
        • Principal Investigator:
          • Marina Cazzaniga
      • Pisa, Italy, 56126
        • Recruiting
        • Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa Chiara
        • Principal Investigator:
          • Carmelo Bengala
      • Ravenna, Italy, 48121
        • Recruiting
        • Ospedale Santa Maria Delle Croci
        • Principal Investigator:
          • Stefano Tamberi
      • Roma, Italy, 168
        • Recruiting
        • Fondazione Policlinico Universitario Agostino Gemelli
        • Principal Investigator:
          • Gennaro Daniele
      • Verona, Italy, 37134
        • Recruiting
        • Centro Ricerche Cliniche di Verona s.r.l.
        • Principal Investigator:
          • Andrea Zivi
  • Japan
      • Fukuoka, Japan, 811-1395
        • Recruiting
        • National Hospital Organization Kyushu Cancer Center
        • Contact:
          • Phone Number: 81120023812
        • Principal Investigator:
          • Eriko Tokunaga
      • Hirakata, Japan, 573-1191
        • Recruiting
        • Kansai Medical University Hospital
        • Contact:
          • Phone Number: 81120023812
        • Principal Investigator:
          • Toshio Shimizu
      • Kyoto, Japan, 606-8507
        • Recruiting
        • Kyoto University Hospital
        • Contact:
          • Phone Number: 81120023812
        • Principal Investigator:
          • TAKAKO NAKAJIMA
      • Kōtō City, Japan, 135-8550
        • Recruiting
        • The Cancer Institute Hospital of JFCR
        • Contact:
          • Phone Number: 81120023812
        • Principal Investigator:
          • Yukinori Ozaki
  • Netherlands
      • Amsterdam, Netherlands, 1066CX
        • Recruiting
        • Netherlands Cancer Institute
        • Principal Investigator:
          • Marloes G.J. van Dongen
      • Rotterdam, Netherlands, 3015GD
        • Recruiting
        • Erasmus MC
        • Principal Investigator:
          • Agnes Jager
  • Spain
      • Barcelona, Spain, 08035
        • Recruiting
        • Hospital Universitari Vall d'Hebron
        • Principal Investigator:
          • Cristina Saura Manich
      • Barcelona, Spain, 08023
        • Recruiting
        • Hospital Quiron Barcelona
        • Principal Investigator:
          • Guzman Alonso Casal
      • Barcelona, Spain, 08023
        • Recruiting
        • South Texas Accelerated Research Therapeutics (START) Barcelona- HM Nou Delfos
        • Principal Investigator:
          • Tatiana Hernandez Guerrero
      • Barcelona, Spain, 08028
        • Recruiting
        • Instituto Oncologico Dr Rosell (IOR)
        • Principal Investigator:
          • Jose Manuel Perez Garcia
      • Logroño, Spain, 26006
        • Recruiting
        • Hospital San Pedro
        • Principal Investigator:
          • Maria Jose de Miguel Luken
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Clinico San Carlos
        • Principal Investigator:
          • Jorge Bartolome Arcilla
      • Madrid, Spain, 28033
        • Recruiting
        • MD Anderson Cancer Center
        • Principal Investigator:
          • Maria Calvo Plaza
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Universitario Fundacion Jimenez Diaz
        • Principal Investigator:
          • Bernard Doger de Speville Uribe
      • Madrid, Spain, 28050
        • Recruiting
        • Hospital Universitario HM Sanchinarro
        • Principal Investigator:
          • Juan Jose Soto
      • Pozuelo de Alarcón, Spain, 28223
        • Recruiting
        • Hospital Universitario Quironsalud Madrid
        • Principal Investigator:
          • Valentina Boni
      • Reus, Spain, 43204
        • Recruiting
        • Hospital Universitari Sant Joan de Reus
        • Principal Investigator:
          • Kepa Amillano Parraga
      • Seville, Spain, 41009
        • Recruiting
        • Hospital Universitario Virgen Macarena
        • Principal Investigator:
          • Luis de la Cruz Merino
  • United States
    • California
      • Los Angeles, California, United States, 90064
        • Recruiting
        • Ellison Clinic at Saint John's
        • Principal Investigator:
          • Reva Basho
      • San Francisco, California, United States, 94143
        • Recruiting
        • UCSF Medical Center at Mission Bay
        • Principal Investigator:
          • Varun Monga
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • University Of Colorado Cancer Center
        • Principal Investigator:
          • Anthony Elias
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Completed
        • Yale-New Haven Hospital
    • Florida
      • Lake Mary, Florida, United States, 32746
        • Completed
        • Florida Cancer Specialists ORLANDO/DDU
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Moffitt Cancer Center
        • Principal Investigator:
          • Aixa Soyano
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Winship Cancer Institute, Emory University
        • Principal Investigator:
          • Manali Bhave
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Recruiting
        • University of Iowa
        • Principal Investigator:
          • Mark Burkard
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Recruiting
        • Louisiana State University Health Sciences Center
        • Principal Investigator:
          • Shou-Ching Tang
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Dejan Juric
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Principal Investigator:
          • Antonio Giordano
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Terminated
        • Barbara Ann Karmanos Cancer Institute
      • Grand Rapids, Michigan, United States, 49546
        • Recruiting
        • Start Midwest
        • Principal Investigator:
          • Manish Sharma
    • Missouri
      • Kansas City, Missouri, United States, 64111-3220
        • Recruiting
        • Saint Luke's Cancer Institute
        • Principal Investigator:
          • Timothy Pluard
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University
        • Principal Investigator:
          • Cynthia Ma
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Principal Investigator:
          • Komal Jhaveri
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • UH Cleveland Medical Center
        • Principal Investigator:
          • Alberto Montero
      • Columbus, Ohio, United States, 43212
        • Recruiting
        • Stefanie Spielman Comprehensive Breast Center
        • Principal Investigator:
          • Robert Wesolowski
    • Oregon
      • Portland, Oregon, United States, 97213
        • Recruiting
        • Providence Cancer Institute Franz Clinic
        • Principal Investigator:
          • David Page
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • Recruiting
        • The West Clinic, PLLC dba West Cancer Center
        • Principal Investigator:
          • Gregory Vidal
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Research Institute
        • Principal Investigator:
          • SMO Sarah Cannon Research Inst.
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • University of Texas Southwestern
        • Principal Investigator:
          • Nisha Unni
      • Dallas, Texas, United States, 75230
        • Completed
        • Mary Crowley Cancer Research Center
      • Dallas, Texas, United States, 75246-2092
        • Recruiting
        • Texas Oncology-Baylor Charles A. Sammons Cancer Center
        • Principal Investigator:
          • Joyce O'Shaughnessy
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas MD Anderson Cancer Center
        • Principal Investigator:
          • Jordi Rodon Ahnert
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • START San Antonio
        • Principal Investigator:
          • Amita Patnaik
    • Utah
      • West Valley City, Utah, United States, 84119
        • Recruiting
        • START Mountain Region
        • Principal Investigator:
          • William McKean
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • USO-Virginia Cancer Specialists, PC
        • Principal Investigator:
          • Alexander Spira

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Dose Escalation (Advanced Solid Tumors)
  • Cohort A0: Advanced Solid tumors expressing PI3Kα mutations
  • Cohort A1: HR+ breast cancer expressing PI3Kα mutations
Drug: STX-478
STX-478 is a mutant-selective PI3Kα inhibitor
Other Names:
  • LY4064809
  • Tersolisib
Experimental: Dose Selection/Expansion: Combination STX-478 + fulvestrant
Cohort B: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Kα mutations
Drug: Fulvestrant
Fulvestrant
Other Names:
  • Faslodex
Drug: STX-478
STX-478 is a mutant-selective PI3Kα inhibitor
Other Names:
  • LY4064809
  • Tersolisib
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
Drug: Fulvestrant
Fulvestrant
Other Names:
  • Faslodex
Drug: Tamoxifen
Tamoxifen
Other Names:
  • Nolvadex
  • Soltamox
Drug: Palbociclib
Palbociclib
Other Names:
  • Ibrance
Drug: Letrozole
Letrozole
Other Names:
  • Femara
Drug: Exemestane
Exemestane
Other Names:
  • Aromasin
Drug: Abemaciclib
Abemaciclib
Other Names:
  • Verzenio
Drug: STX-478
STX-478 is a mutant-selective PI3Kα inhibitor
Other Names:
  • LY4064809
  • Tersolisib
Drug: Ribociclib
Ribociclib
Other Names:
  • Kisqali
Drug: Anastrozole
Anastrozole
Other Names:
  • Arimidex
Drug: Imlunestrant
Imlunestrant
Other Names:
  • Inluriyo
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
Drug: STX-478
STX-478 is a mutant-selective PI3Kα inhibitor
Other Names:
  • LY4064809
  • Tersolisib
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
Drug: Metformin
Metformin
Drug: Fulvestrant
Fulvestrant
Other Names:
  • Faslodex
Drug: Palbociclib
Palbociclib
Other Names:
  • Ibrance
Drug: Letrozole
Letrozole
Other Names:
  • Femara
Drug: Exemestane
Exemestane
Other Names:
  • Aromasin
Drug: Abemaciclib
Abemaciclib
Other Names:
  • Verzenio
Drug: STX-478
STX-478 is a mutant-selective PI3Kα inhibitor
Other Names:
  • LY4064809
  • Tersolisib
Drug: Ribociclib
Ribociclib
Other Names:
  • Kisqali
Drug: Anastrozole
Anastrozole
Other Names:
  • Arimidex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants who experience at least 1 Dose Limiting Toxicity (DLT)
Time Frame: First 28 days of treatment
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
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
12 months
Incidence of TEAEs/SAEs ≥ grade 2
Time Frame: 12 months
12 months
Frequency of TEAEs according to CTCAE v5.0 criteria
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Cmax of STX-478
Time Frame: 12 months
12 months
AUC(0-inf) of STX-478
Time Frame: 12 months
12 months
AUC(0-t) of STX-478
Time Frame: 12 months
12 months
AUC(0-τ) of STX-478
Time Frame: 12 months
12 months
Change from baseline in ctDNA levels
Time Frame: 12 months
12 months
Changes in circulating markers of glucose metabolism as assessed by changes in circulating glycosylated hemoglobin (HbA1c)
Time Frame: 12 months
12 months
Changes in circulating markers of glucose metabolism as assessed by circulating fasting plasma glucose
Time Frame: 12 months
12 months
Changes in circulating markers of glucose metabolism as assessed by circulating C-peptide
Time Frame: 12 months
12 months
Change in ECOG performance status
Time Frame: 12 months
12 months
Disease Control Rate (DCR) per RECIST v1.1, measured as percentage of participants with Complete Response
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eli Lilly and Company

Investigators

  • Study Director: 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 record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 17, 2023

Primary Completion (Estimated)

July 1, 2030

Study Completion (Estimated)

July 1, 2030

Study Registration Dates

First Submitted

March 1, 2023

First Submitted That Met QC Criteria

March 13, 2023

First Posted (Actual)

March 14, 2023

Study Record Updates

Last Update Posted (Actual)

July 7, 2026

Last Update Submitted That Met QC Criteria

July 3, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 27691
  • STX-478-101 (Other Identifier: Scorpion Therapeutics, Inc)
  • 2023-000442-41 (EudraCT Number)
  • 2023-504807-94-00 (Ctis: EU CT Number)
  • J6M-OX-JSGA (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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