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NCT Number: NCT05683418

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

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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Key information

Conditions

HR+/HER2-negative Breast Cancer Breast Diseases Breast Neoplasms Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hereditary Sensory and Autonomic Neuropathies Heredodegenerative Disorders, Nervous System Neoplasms Neoplasms by Site Nervous System Diseases Nervous System Malformations Neurodegenerative Diseases Neuromuscular Diseases Peripheral Nervous System Diseases Polyneuropathies Skin Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

Primary location

Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON, Barcelona, Spain

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About this study

This study will be conducted in two parts: a dose finding portion to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) of TOS-358 administered orally on once a day (QD) and twice daily (BID) schedules, and a dose expansion portion to evaluate safety and tolerability in tumor-specific cohorts administered TOS-358 at the recommended phase 2 dose and schedule.

Women with histologically confirmed diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer with known PIK3CA mutations or amplifications and who meet all of the eligibility criteria will be enrolled in the study.

In the dose finding portion of the study, TOS-358 will be evaluated as a single-agent at multiple dose levels administered orally until disease progression, unacceptable toxicity, or until meeting any other reason for discontinuation as specified in the protocol. In the Phase 1b portion, TOS-358 will be combined with fulvestrant +/- CDK4/6i.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

TOS-358

Drug

Covalent Phosphoinositide-3-Kinase (PI3K)-alpha Inhibitor

Fulvestrant

Drug

Intramuscular SERD at standard doses

Palbociclib

Drug

CDK4/6 inhibitor at standard doses

Ribociclib

Drug

CDK4/6 inhibitor at standard doses

Primary outcomes

  1. Determine the rate of dose-limiting toxicities (DLTs)

    Time frame: First 21 days of treatment

  2. Incidence and severity of adverse events (AEs) and specific laboratory abnormalities graded according to NCI CTCAE v5

    Time frame: Start of treatment to 30 days after last dose

Secondary outcomes

  1. ORR and duration of tumor control

    Time frame: 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

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials

CONTACT

[email protected]

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Sponsors and collaborators

Lead sponsor

Totus Medicines

Industry

Registry information

Official study 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

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Jan 13, 2023
Registry last updated
Apr 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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