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STX-478

Phase 1

Breast Cancer | Small molecule | Oncology |Eli Lilly and Company|Last Updated: Jun 4, 2026

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
CONTROLLEDBiomarker
Total Trials1
Total Enrollment880
FDA Designations
No designations recorded
Clinical Trials (1)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT05768139First-in-Human Study of Tersolisib (STX-478) as Monotherapy and in Combination With Other Antineoplastic Agents in Participants With Advanced Solid TumorsPHASE1 RECRUITING 880Apr 17, 2023Jul 1, 2030Jun 4, 202665 United States, Belgium +7
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Study Endpoints
Primary Endpoints
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
Cmax of STX-478
12 months
AUC(0-inf) of STX-478
12 months
AUC(0-t) of STX-478
12 months
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Study Design & Arms
AllocationNON_RANDOMIZED
MaskingNONE
ModelSEQUENTIAL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
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
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 — N/A
SexALL
Healthy VolunteersNo
Study Sites65

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...

Countries:United StatesBelgiumFranceGermanyIrelandItalyJapanNetherlandsSpain
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Competitive Landscape -Breast Cancer 408 trials
CompanyTickerTrialsLead PhaseDrugs
Merck & Co., Inc.MRK12PHASE3Pembrolizumab, Paclitaxel, Doxorubicin, Epirubicin, Cyclophosphamide
AstraZeneca PLCAZN47PHASE3Fulvestrant, Capivasertib, Trastuzumab Deruxtecan, Paclitaxel, Trastuzumab
Gilead Sciences, Inc.GILD13PHASE3Sacituzumab Govitecan-hziy, Eribulin, Capecitabine Product, Gemcitabine, Vinorelbine
Eli Lilly and CompanyLLY27PHASE3Abemaciclib, Standard Adjuvant Endocrine Therapy, Imlunestrant, Tamoxifen, Anastrozole
BioNTech SE Sponsored ADRBNTX7PHASE3DB-1303/BNT323, T-DM1, Capecitabine, Paclitaxel, Nab-paclitaxel
Novartis AG Sponsored ADRNVS30PHASE3Ribociclib, Alpelisib, Fulvestrant, Trastuzumab, Pertuzumab
Olema Pharmaceuticals, Inc.OLMA5PHASE3Palazestrant, Fulvestrant, Anastrozole, Letrozole, Exemestane
Pfizer Inc.PFE34PHASE3ARV-471, Fulvestrant, PF-07220060, letrozole, abemaciclib
BeOne Medicines Ltd. Sponsored ADRONC6PHASE3BGB-43395, Letrozole, Abemaciclib, Palbociclib, Ribociclib
Jazz Pharmaceuticals Public Limited CompanyJAZZ3PHASE3Zanidatamab, Trastuzumab, Eribulin, Vinorelbine, Gemcitabine
Celcuity Inc.CELC3PHASE3Gedatolisib, Palbociclib, Fulvestrant, Alpelisib, Arm A: Gedatolisib + Palbociclib + Fulvestrant
Relay Therapeutics, Inc.RLAY2PHASE3RLY-2608, Capivasertib, Fulvestrant, Palbociclib, Ribociclib
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, Pembrolizumab, Axatilimab
Natera, Inc.NTRA3PHASE2Discontinuation of the anti-HER2 maintenance therapy
Puma Biotechnology, Inc.PBYI3PHASE2Neratinib, Loperamide, Colesevelam, Alisertib, Endocrine therapy
Immutep Ltd Sponsored ADRIMMP1PHASE2eftilagimod alpha, Paclitaxel
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Recent Changes (Last 90 Days)
LOWJun 4, 2026NCT05768139lastUpdatePostDate: changed
LOWJun 4, 2026NCT05768139lastUpdatePostDate: changed
LOWJun 4, 2026NCT05768139lastUpdatePostDate: changed
LOWJun 4, 2026NCT05768139lastUpdatePostDate: changed
MEDIUMMay 26, 2026NCT05768139Enrollment: 720 → 880
LOWMay 24, 2026NCT05768139studyFirstPostDate: changed