A Study to Evaluate the Safety and Tolerability of TOS-358 in Women With HR+ HER2- Breast Cancer

NCT05683418
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
241
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Lead sponsor
Totus Medicines
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Start date
2023-02-15
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Number of sites
18
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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)
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Short title
A Study to Evaluate the Safety and Tolerability of TOS-358 in Women With HR+ HER2- Breast Cancer
clinicaltrials.gov
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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2027-12-01
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First posted
2023-01-13
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Registry last updated
2026-04-22
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Primary completion date
2027-12-01
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Start date
2023-02-15
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Participants
241
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Participant count basis
Estimated
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Planned participants
241
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Protocol amendments
4
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Number of sites
18
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Data monitoring committee
No
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Registry sponsor category
Industry
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Lead sponsor
Totus Medicines
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05683418
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ClinicalTrials.gov ID
NCT05683418
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Registry record
Open registry record
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Allocation
Not randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  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

  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
clinicaltrials.gov

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
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  • 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
clinicaltrials.gov

  • 2023
  • 2023-505346-26-01
Sources for references
clinicaltrials.gov

Related records

Drugs (3)

Lead sponsors (1)

Conditions (1)

Targets (4)