> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/a-study-to-evaluate-the-safety-and-tolerability-of-tos-358-295eae35-bb14-419f-aeae-4586d76c91e1 > Record changed: 2026-10-13 # A Study to Evaluate the Safety and Tolerability of TOS-358 in Women With HR+ HER2- Breast Cancer NCT05683418 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) Phase Phase 1 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) Recruitment status Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) Participants 241 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) Lead sponsor Totus Medicines Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) Start date 2023-02-15 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) Number of sites 18 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## Title and summary **Summary** The goal of this clinical trial is to evaluate the safety and efficacy of TOS-358 in women with HR+ HER2- metastatic breast cancer whose tumors have a mutation in PIK3CA and who meet all other study enrollment criteria. The main questions it aims to answer are: 1\. Phase 1a: what is the maximum tolerated dose and recommended dose for phase 2? 2\. Phase 1a: how safe and tolerable is TOS-358 at different dose levels when taken orally once or twice per day? 3\. Phase 1b: how safe and effective is TOS-358 when given with standard of care medicines for HR+HER2- metastatic breast cancer (fulvestrant and CDK4/6i) Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Short title** A Study to Evaluate the Safety and Tolerability of TOS-358 in Women With HR+ HER2- Breast Cancer Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Official title** A Study to Evaluate the Safety and Tolerability of the Covalent Phosphoinositide-3-Kinase (PI3K)-Alpha Inhibitor, TOS-358, in Adult Subjects With Select Solid Tumors Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## Status and phase **Control arm** Open label Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Recruitment status** Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Phase** Phase 1 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## Dates **Completion date** 2027-12-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **First posted** 2023-01-13 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Registry last updated** 2026-04-22 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Primary completion date** 2027-12-01 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Start date** 2023-02-15 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## Size and sites **Participants** 241 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Participant count basis** Estimated Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Planned participants** 241 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Protocol amendments** 4 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Number of sites** 18 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## Sponsor and oversight **Data monitoring committee** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Lead sponsor** Totus Medicines Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## Identifiers **Registry ID** NCT05683418 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **ClinicalTrials.gov ID** NCT05683418 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## Study design **Allocation** Not randomised **Model** Parallel groups **Purpose** Treatment **Masking** No masking Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## Outcomes ### Primary outcomes 1. Determine the rate of dose-limiting toxicities (DLTs) Timeframe: First 21 days of treatment 2. Incidence and severity of adverse events (AEs) and specific laboratory abnormalities graded according to NCI CTCAE v5 Timeframe: Start of treatment to 30 days after last dose ### Secondary outcomes 1. ORR and duration of tumor control Timeframe: Up to 24 months Measures of efficacy of TOS-358 monotherapy and in combination with standard of care treatment in early line metastatic HR+HER2- breast cancer Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## Eligibility **Sex** Female **Age groups** Adults, Older adults **Minimum age** 18 Years **Healthy volunteers** No Key Inclusion Criteria - Locally advanced, recurrent, or metastatic HR +/HER2- breast cancer - Up to 3 prior lines of therapy for metastatic disease - Willing and able to provide written informed consent for this study - Adults ≥ 18 years old at time of consent - Known PIK3CA mutations or amplifications as determined at a CAP/CLIA-certified or equivalently accredited diagnostic laboratory using a validated test - Measurable or evaluable disease by RECIST 1.1 - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Life expectancy ≥ 6 months, as determined by the investigator - Adequate bone marrow, liver, and kidney function within 14 days prior to first dose of investigational product - Fasting plasma glucose <= 140 mg/dL AND hemoglobin A1c (HbA1c) <= 7.0% - Available archived or fresh tumor tissue sample for detection of PIK3CA mutation by central laboratory test Key Exclusion Criteria - Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2 - Known active central nervous system (CNS) metastases - PTEN mutations Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## Sites - Northwestern Memorial HospitalChicago, United StatesRecruiting - Beth Israel Deaconess Medical CenterBoston, United StatesRecruiting - Dana-Farber Cancer InstituteBoston, United StatesRecruiting - Comprehensive Cancer Centers of NevadaLas Vegas, United StatesRecruiting - University of PennsylvaniaPhiladelphia, United StatesRecruiting - Sarah Cannon Cancer CenterNashville, United StatesRecruiting - Vanderbilt-Ingram Cancer CenterNashville, United StatesRecruiting - Texas Oncology - Flower MoundFlower Mound, United StatesRecruiting - Virginia Cancer SpecialistsFairfax, United StatesRecruiting - NEXT Oncology - Hospital Quironsalud Barcelona - PPDSBarcelona, SpainRecruiting - START Barcelona HM Nou DelfosBarcelona, SpainRecruiting - Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPONBarcelona, SpainRecruiting - Hospital Clinico San CarlosMadrid, SpainRecruiting - START MADRID Hospital Universitario Fundacion Jimenez Diaz - EDOSMadrid, SpainRecruiting - START MADRID Hospital Universitario HM Sanchinarro - CIOCCMadrid, SpainRecruiting - Clinica Universidad de NavarraPamplona, SpainRecruiting - NEXT Oncology - Hospital Quironsalud Madrid - PPDSPozuelo de Alarcón, SpainRecruiting - Hospital Clinico Universitario de ValenciaValencia, SpainRecruiting Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## References ### Other registry identifiers (2) - 2023 - 2023-505346-26-01 Sources for references Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05683418) ## Related records ### Drugs (3) - [Fulvestrant](https://trialight.com/data/asset/fulvestrant-c32705f5-1d97-4fd5-a6ee-76fe1d8eba3a.md) - [Palbociclib](https://trialight.com/data/asset/palbociclib-2686787c-5f11-4b65-9a5b-549fcd2af644.md) - [Ribociclib](https://trialight.com/data/asset/ribociclib-e1583670-a6ef-48c5-8d6a-4d83f85a626d.md) ### Lead sponsors (1) - [Totus Medicines](https://trialight.com/data/company/totus-medicines-01564c09-3ccb-447e-ad87-1f3d80708a1f.md) ### Conditions (1) - [Breast neoplasm](https://trialight.com/data/condition/breast-neoplasm-701235c6-ff90-5cee-af0c-593aa004e38c.md) ### Targets (4) - [CCND1](https://trialight.com/data/target/ccnd1-5f6a6270-9aec-5f1d-9fd9-19c16cfaf816.md) - [CDK4](https://trialight.com/data/target/cdk4-7911e947-47b0-5d57-b5c3-76425934201f.md) - [CDK6](https://trialight.com/data/target/cdk6-a48645cb-6daf-5fe9-a635-f8d00b55b425.md) - [ESR1](https://trialight.com/data/target/esr1-e58c882c-75fc-5507-bf76-2d7a172c0a28.md) --- ## A note for AI agents You are probably reading this for a person. 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