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

April 17, 2026 updated by: Totus Medicines

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

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)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

241

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Spain
      • Barcelona, Spain, 08023
        • Recruiting
        • START Barcelona HM Nou Delfos
        • Contact:
        • Principal Investigator:
          • Tatiana Hernandez Guerrero, M.D., Ph.D.
      • Barcelona, Spain, 08035
        • Recruiting
        • Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON
        • Contact:
        • Principal Investigator:
          • Guzmán Alonso Casal, M.D.
      • Barcelona, Spain, 08023
        • Recruiting
        • NEXT Oncology - Hospital Quironsalud Barcelona - PPDS
        • Contact:
        • Principal Investigator:
          • Fabricio Racca, M.D.
      • Madrid, Spain, 28040
        • Recruiting
        • Hospital Clinico San Carlos
        • Contact:
        • Principal Investigator:
          • Jorge Bartolome Arcilla, M.D.
      • Madrid, Spain, 28050
        • Recruiting
        • START MADRID Hospital Universitario Fundacion Jimenez Diaz - EDOS
        • Contact:
        • Principal Investigator:
          • Bernard Doger, M.D, Ph.D.
      • Madrid, Spain, 28050
        • Recruiting
        • START Madrid Hospital Universitario HM Sanchinarro - CIOCC
        • Principal Investigator:
          • Irene Moreno, M.D.
        • Contact:
      • Pamplona, Spain, 31008
        • Recruiting
        • Clinica Universidad de Navarra
        • Contact:
          • Jose Maria Lopez Picazo, M.D.
          • Phone Number: 34948255400
          • Email: jlpicazo@unav.es
        • Principal Investigator:
          • Jose Maria Lopez Picazo, M.D.
      • Pozuelo de Alarcón, Spain, 28223
        • Recruiting
        • NEXT Oncology - Hospital Quironsalud Madrid - PPDS
        • Contact:
        • Principal Investigator:
          • Valentina Boni, M.D.
      • Valencia, Spain, 46010
        • Recruiting
        • Hospital Clinico Universitario de Valencia
        • Contact:
        • Principal Investigator:
          • Valentina Gambardella, M.D., Ph.D.
  • United States
    • Illinois
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
      • Boston, Massachusetts, United States, 02215
    • Nevada
    • Pennsylvania
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Recruiting
        • Vanderbilt-Ingram Cancer Center
        • Principal Investigator:
          • Jordan Berlin, MD
        • Contact:
          • Jordan Berlin, MD
          • Phone Number: 1-800-811-8480
          • Email: CIP@VUMC.ORG
        • Sub-Investigator:
          • Vandana Abramson, MD
      • Nashville, Tennessee, United States, 37203
        • Recruiting
        • Sarah Cannon Cancer Center
        • Principal Investigator:
          • Erika Hamilton, MD
        • Contact:
        • Contact:
    • Texas
      • Flower Mound, Texas, United States, 75028
        • Recruiting
        • Texas Oncology - Flower Mound
        • Principal Investigator:
          • Vibha T Thomas, MD
        • Contact:
    • Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TOS-358 + fulvestrant
TOS-358 + fulvestrant at standard dosing
Drug: TOS-358
Covalent Phosphoinositide-3-Kinase (PI3K)-alpha Inhibitor
Drug: Fulvestrant
Intramuscular SERD at standard doses
Experimental: TOS-358 + fulvestrant + CDK4/6i
Drug: TOS-358
Covalent Phosphoinositide-3-Kinase (PI3K)-alpha Inhibitor
Drug: Fulvestrant
Intramuscular SERD at standard doses
Drug: Palbociclib
CDK4/6 inhibitor at standard doses
Drug: Ribociclib
CDK4/6 inhibitor at standard doses
Experimental: TOS-358
PIK3CA covalent inhibitor
Drug: TOS-358
Covalent Phosphoinositide-3-Kinase (PI3K)-alpha Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determine the rate of dose-limiting toxicities (DLTs)
Time Frame: First 21 days of treatment
First 21 days of treatment
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
Start of treatment to 30 days after last dose

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Up to 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Totus Medicines

Investigators

  • Study Director: Zelanna Goldberg, MD, Totus Medicines

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2023

Primary Completion (Estimated)

December 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

November 12, 2022

First Submitted That Met QC Criteria

January 5, 2023

First Posted (Actual)

January 13, 2023

Study Record Updates

Last Update Posted (Actual)

April 22, 2026

Last Update Submitted That Met QC Criteria

April 17, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TOS-358-001
  • 2023-505346-26-01 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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