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STX-478

Phase 1

Breast Cancer | Small molecule | Oncology |Eli Lilly and Company|Last Updated: Jul 7, 2026

Target and mechanism

Molecular targetPIK3CA
Target classGene
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

CONTROLLED
Total Trials1
Total Enrollment880

FDA Designations

No designations recorded

Clinical trial landscape

STX-478 · 2 trials · 3 indications

Phase 1 2
NCT06901336A Study of LY4064809 [14C]-STX-478 in Healthy Male ParticipantsHealthy
COMPLETED8 Analytics
NCT05768139First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid TumorsBreast Cancer
RECRUITING880 Analytics
PHASE1COMPLETED
A Study of LY4064809 [14C]-STX-478 in Healthy Male Participants
HealthyUnlock trial analytics
PHASE1RECRUITING
First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid Tumors
Breast CancerUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of the Total Radioactive Dose in Urinary, Fecal, and Urinary and Fecal Combined Excretion
Baseline, Up to Day 29
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 Endpoints

Pharmacokinetics (PK): Maximum Concentration (Cmax) of 14C and STX-478
Predose up to Day 29 Post Dose
PK: Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC 0- inf) of 14C and STX-478
Predose up to Day 29 Post Dose
Total Radioactivity Recovered in Urine and Feces
Predose up to Day 29 Post Dose
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Study Design & Arms

AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeBASIC_SCIENCE

Treatment Arms

ArmTypeDescription
[14C]-STX-478EXPERIMENTALHealthy participants will receive a single dose of \[14C\]-STX-478.
Dose Escalation (Advanced Solid Tumors)EXPERIMENTAL* Cohort A0: Advanced Solid tumors expressing PI3Kα mutations * Cohort A1: HR+ breast cancer expressing PI3Kα mutations
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
Dose Selection/Expansion: Combination STX-478 + fulvestrantEXPERIMENTALCohort B: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Kα mutations
Dose Selection/Expansion CombinationEXPERIMENTALSTX-478 + Endocrine therapy + CDK4/6 inhibitor Cohort C/D/E: HR+/HER2- or HR+/HER2low breast cancer expressing PI3Ka mutations
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

Interventions

NameTypeDescription
[14C]-STX-478DRUGoral administration
STX-478DRUGSTX-478 is a mutant-selective PI3Kα inhibitor
FulvestrantDRUGFulvestrant
RibociclibDRUGRibociclib
PalbociclibDRUGPalbociclib
LetrozoleDRUGLetrozole
AnastrozoleDRUGAnastrozole
ExemestaneDRUGExemestane
TamoxifenDRUGTamoxifen
AbemaciclibDRUGAbemaciclib
ImlunestrantDRUGImlunestrant
MetforminDRUGMetformin
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Eligibility Criteria

Age Range18 Years to 55 Years
SexMALE
Healthy VolunteersYes
Study Sites1

Inclusion Criteria: * Body mass index (BMI) ≥ 18.0 kg/m2 and ≤ 32.0 kg/m2 at Screening; body weight ≥ 55.0 kg and ≤ 100.0 kg at Screening. * Negative serology results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) and human immunodeficiency virus antibody and antige...

Countries:United StatesBelgiumFranceGermanyIrelandItalyJapanNetherlandsSpain
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Competitive Landscape -Breast Cancer 402 trials

Top 20 of 92 competitors

CompanyTickerTrialsLead PhaseDrugs
AstraZeneca PLCAZN47PHASE3Fulvestrant, Capivasertib
Merck & Co., Inc.MRK12PHASE3Pembrolizumab, Paclitaxel, Doxorubicin, Epirubicin, Cyclophosphamide
Eli Lilly and CompanyLLY27PHASE3Abemaciclib, Standard Adjuvant Endocrine Therapy
BioNTech SE Sponsored ADRBNTX7PHASE3DB-1303/BNT323, T-DM1
Gilead Sciences, Inc.GILD13PHASE3Sacituzumab Govitecan-hziy, Eribulin, Capecitabine Product, Gemcitabine, Vinorelbine
Novartis AG Sponsored ADRNVS30PHASE3Ribociclib
Pfizer Inc.PFE34PHASE3ARV-471, Fulvestrant
BeOne Medicines Ltd. Sponsored ADRONC5PHASE3BGB-43395, Letrozole, Abemaciclib, Palbociclib, Ribociclib
Olema Pharmaceuticals, Inc.OLMA5PHASE3Palazestrant, Fulvestrant, Anastrozole, Letrozole, Exemestane
Jazz Pharmaceuticals Public Limited CompanyJAZZ3PHASE3Zanidatamab, Trastuzumab, Eribulin, Vinorelbine, Gemcitabine
Celcuity Inc.CELC3PHASE3Gedatolisib, Palbociclib, Fulvestrant, Alpelisib
Relay Therapeutics, Inc.RLAY2PHASE3Zovegalisib, Capivasertib, Fulvestrant
GSK plc Sponsored ADRGSK2PHASE3Niraparib
Greenwich LifeSciences, Inc.GLSI1PHASE3GLSI-100
Bristol-Myers Squibb CompanyBMY5PHASE2Iza-bren, Nab-paclitaxel, Paclitaxel, Capecitabine, Carboplatin
BriaCell Therapeutics CorpBCTX2PHASE3SV-BR-1-GM, Cyclophosphamide, Interferon infiltration of the inoculation site, Retifanlimab, Treatment of Physician's Choice
Incyte CorporationINCY4PHASE2Ruxolitinib, Capecitabine, Regorafenib
Natera, Inc.NTRA3PHASE2Discontinuation of the anti-HER2 maintenance therapy
Puma Biotechnology, Inc.PBYI3PHASE2Neratinib, Loperamide, Colesevelam
Atossa Therapeutics, Inc.ATOS1PHASE2endoxifen, goserelin
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Recent Changes (Last 90 Days)

LOWJul 7, 2026NCT05768139lastUpdatePostDate: changed
LOWJul 7, 2026NCT05768139lastUpdatePostDate: changed

Frequently asked questions about STX-478

What is STX-478 used for?

STX-478 is an investigational small molecule being studied for the treatment of advanced solid tumors, including breast cancer. It is currently in Phase 1 clinical trials, both as a monotherapy and in combination with other antineoplastic agents. STX-478 is not yet approved by the FDA and remains in clinical development.

What does STX-478 target?

STX-478 targets the PIK3CA gene. It is being studied in patients with advanced solid tumors, including breast cancer. The drug is designed to interfere with the function of this gene, which is often mutated in cancer. However, the exact mechanism of action is not fully described in the available clinical trial information.

Who makes STX-478?

STX-478 is being developed by Eli Lilly and Company, a pharmaceutical company listed on the stock exchange under the ticker symbol LLY. The company is conducting clinical trials to evaluate the safety and efficacy of this investigational drug in patients with advanced solid tumors.

What phase is STX-478 in?

STX-478 is currently in Phase 1 clinical trials. There are two Phase 1 studies: one in patients with advanced solid tumors and another in healthy male participants. The drug is investigational and has not yet received FDA approval. It is still in the early stages of clinical development.

What clinical trials is STX-478 in?

STX-478 is being studied in two Phase 1 clinical trials. The first, NCT05768139, is a first-in-human study of STX-478 as monotherapy and in combination with other antineoplastic agents in participants with advanced solid tumors, including breast cancer. The second, NCT06901336, is a study of LY4064809 [14C]-STX-478 in healthy male participants.

Is STX-478 the same as LY4064809?

STX-478 is also known as LY4064809 in some clinical trial contexts. For example, a study of LY4064809 [14C]-STX-478 in healthy participants refers to the same drug. This alternative name is used in the clinical trial registry to identify the compound.