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

NCT05768139 · Eli Lilly and Company
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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
About this study
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
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 target: 880 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2023-04-17
Estimated completion: 2030-07
Last updated: 2026-06-04
Interventions
Drug: STX-478Drug: FulvestrantDrug: RibociclibDrug: PalbociclibDrug: LetrozoleDrug: AnastrozoleDrug: ExemestaneDrug: TamoxifenDrug: AbemaciclibDrug: ImlunestrantDrug: Metformin
Primary outcomes
  • 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)
Sponsor
Eli Lilly and Company · industry
Contacts & investigators
ContactTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or · contact · LillyTrials@Lilly.com · 1-317-615-4559
ContactPhysicians interested in becoming principal investigators please contact · contact · clinical_inquiry_hub@lilly.com
InvestigatorCall 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) · study_director, Eli Lilly and Company
All locations (65)
Ellison Clinic at Saint John'sRecruiting
Los Angeles, California, United States
UCSF Medical Center at Mission BayRecruiting
San Francisco, California, United States
University of Colorado Cancer CenterRecruiting
Aurora, Colorado, United States
Yale-New Haven HospitalCompleted
New Haven, Connecticut, United States
Florida Cancer Specialists ORLANDO/DDUCompleted
Lake Mary, Florida, United States
Moffitt Cancer CenterRecruiting
Tampa, Florida, United States
Winship Cancer Institute, Emory UniversityRecruiting
Atlanta, Georgia, United States
University of IowaRecruiting
Iowa City, Iowa, United States
Louisiana State University Health Sciences CenterRecruiting
New Orleans, Louisiana, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Dana-Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer InstituteTerminated
Detroit, Michigan, United States
START MidwestRecruiting
Grand Rapids, Michigan, United States
Saint Luke's Cancer InstituteRecruiting
Kansas City, Missouri, United States
Washington UniversityRecruiting
St Louis, Missouri, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
UH Cleveland Medical CenterRecruiting
Cleveland, Ohio, United States
Stefanie Spielman Comprehensive Breast CenterRecruiting
Columbus, Ohio, United States
Providence Cancer Institute Franz ClinicRecruiting
Portland, Oregon, United States
The West Clinic, PLLC dba West Cancer CenterRecruiting
Germantown, Tennessee, United States
Sarah Cannon Research InstituteRecruiting
Nashville, Tennessee, United States
Mary Crowley Cancer Research CenterCompleted
Dallas, Texas, United States
Texas Oncology-Baylor Charles A. Sammons Cancer CenterRecruiting
Dallas, Texas, United States
University of Texas SouthwesternNot Yet Recruiting
Dallas, Texas, United States
University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
START San AntonioRecruiting
San Antonio, Texas, United States
START Mountain RegionRecruiting
West Valley City, Utah, United States
USO-Virginia Cancer Specialists, PCRecruiting
Fairfax, Virginia, United States
Institut Jules BordetRecruiting
Anderlecht, Belgium
UZ LeuvenRecruiting
Leuven, Belgium
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud OuestRecruiting
Bordeaux, France
Centre Leon BerardRecruiting
Lyon, France
Institut Paoli-CalmettesRecruiting
Marseille, France
Centre Antoine-LacassagneRecruiting
Nice, France
Institut Claudius RegaudRecruiting
Toulouse, France
Gustave RoussyRecruiting
Villejuif, France
Universitätsklinikum ErlangenNot Yet Recruiting
Erlangen, Germany
Mater Misericordiae HospitalRecruiting
Dublin, Ireland
Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare ArrigoRecruiting
Alessandria, Italy
Spedali Civili di BresciaNot Yet Recruiting
Brescia, Italy
Istituto Nazionale per lo Studio e la Cura dei TumoriRecruiting
Milan, Italy
Istituto Europeo di OncologiaRecruiting
Milan, Italy
Fondazione IRCCS San Gerardo dei TintoriRecruiting
Monza, Italy
Azienda Ospedaliero Universitaria Pisana - Stabilimento Santa ChiaraRecruiting
Pisa, Italy
Ospedale Santa Maria delle CrociRecruiting
Ravenna, Italy
Fondazione Policlinico Universitario Agostino GemelliRecruiting
Roma, Italy
Centro Ricerche Cliniche di Verona s.r.l.Recruiting
Verona, Italy
National Hospital Organization Kyushu Cancer CenterRecruiting
Fukuoka, Japan
Kansai Medical University HospitalRecruiting
Hirakata, Japan
The Cancer Institute Hospital of JFCRRecruiting
Kōtō City, Japan
Kyoto University HospitalRecruiting
Kyoto, Japan
Netherlands Cancer InstituteRecruiting
Amsterdam, Netherlands
Erasmus MCRecruiting
Rotterdam, Netherlands
Hospital Quiron BarcelonaRecruiting
Barcelona, Spain
South Texas Accelerated Research Therapeutics (START) Barcelona- HM Nou DelfosRecruiting
Barcelona, Spain
Instituto Oncologico Dr Rosell (IOR)Recruiting
Barcelona, Spain
Hospital Universitari Vall d'HebronRecruiting
Barcelona, Spain
Hospital San PedroRecruiting
Logroño, Spain
MD Anderson Cancer CenterRecruiting
Madrid, Spain
Hospital Clinico San CarlosRecruiting
Madrid, Spain
Hospital Universitario Fundación Jiménez DíazRecruiting
Madrid, Spain
Hospital Universitario HM SanchinarroRecruiting
Madrid, Spain
Hospital Universitario Quironsalud MadridRecruiting
Pozuelo de Alarcón, Spain
Hospital Universitari Sant Joan de ReusRecruiting
Reus, Spain
Hospital Universitario Virgen MacarenaRecruiting
Seville, Spain
First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors · TrialPath