A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With HR+ Breast Cancer and Other Select Solid Tumors

NCT ID: NCT05683418

Last Updated: 2025-07-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

241 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-15

Study Completion Date

2026-12-31

Brief Summary

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The goal of this clinical trial is to evaluate the safety of TOS-358 in adults with select solid tumors who meet study enrollment criteria. The main questions it aims to answer are:

1. what is the maximum tolerated dose and recommended dose for phase 2?
2. how safe and tolerable is TOS-358 at different dose levels when taken orally once or twice per day?

Detailed Description

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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.

Adult subjects with histologically confirmed diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2) negative breast cancer, squamous cell carcinoma of the head and neck, cancer of the bladder, or endometrial 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.

Conditions

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Squamous Cell Carcinoma of Head and Neck Endometrial Cancer HR+/HER2-negative Breast Cancer Bladder Cancer

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

TOS-358 Single Agent Arm:

Part 1 (multiple ascending doses, QD or BID): locally advanced, recurrent or metastatic HR+ breast, endometrial, urothelial or squamous cell carcinoma of the head and neck, with PIK3CA mutation per local assessment; Part 2 (RP2D determined in Part 1) Patients with locally advanced, recurrent or metastatic HR+ breast cancer with PIK3CA mutation per local assessment will be enrolled protocol defined groups.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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TOS-358 Single Agent Arm

Multiple doses of TOS-358 for oral administration.

Group Type EXPERIMENTAL

TOS-358

Intervention Type DRUG

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

Interventions

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TOS-358

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Locally advanced, recurrent, or metastatic, incurable (any number of previous lines of therapy is allowed), histologically or cytologically confirmed; HR +/HER2- breast cancer; squamous cell carcinoma of the head and neck; urothelial cancer; or endometrial cancer with no more than 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 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

Exclusion Criteria

* Recent systemic anticancer treatment prior to start of treatment (EXCEPTION: Patients with breast cancer who were receiving a fulvestrant-containing regimen at the time of informed consent may remain on fulvestrant while receiving study treatment)
* For non-breast cancer: prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway,
* Has an established diagnosis of diabetes mellitus type 1 or has uncontrolled diabetes mellitus type 2 requiring antihyperglycemic medication
* Known active central nervous system (CNS) metastases.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Totus Medicines

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Zelanna Goldberg, MD

Role: STUDY_DIRECTOR

Totus Medicines

Locations

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University of Southern California, Norris Comprehensive Cancer Center

Los Angeles, California, United States

Site Status RECRUITING

Northwestern Memorial Hospital

Chicago, Illinois, United States

Site Status RECRUITING

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Stephenson Cancer Center

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, United States

Site Status RECRUITING

Virginia Cancer Specialists, PC

Fairfax, Virginia, United States

Site Status RECRUITING

NEXT Oncology - Hospital Quironsalud Barcelona - PPDS

Barcelona, , Spain

Site Status RECRUITING

START Barcelona HM Nou Delfos

Barcelona, , Spain

Site Status RECRUITING

Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON

Barcelona, , Spain

Site Status RECRUITING

Hospital Clinico San Carlos

Madrid, , Spain

Site Status RECRUITING

START MADRID Hospital Universitario Fundacion Jimenez Diaz - EDOS

Madrid, , Spain

Site Status RECRUITING

START MADRID Hospital Universitario HM Sanchinarro - CIOCC

Madrid, , Spain

Site Status RECRUITING

Clinica Universidad de Navarra

Pamplona, , Spain

Site Status RECRUITING

NEXT Oncology - Hospital Quironsalud Madrid - PPDS

Pozuelo de Alarcón, , Spain

Site Status RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, , Spain

Site Status RECRUITING

Countries

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United States Spain

Central Contacts

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Clinical Trials

Role: CONTACT

Please e-mail

Facility Contacts

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Xiomara Menendez, RN

Role: primary

Study Coordinator

Role: primary

312-695-1301

Andreas Varkaris, MD, PhD

Role: primary

617-724-4000

Susan Gotthardt

Role: primary

617-975-7452

Emily McClure, RN

Role: primary

857-215-0180

Christina Caldwell, LPN

Role: primary

405-271-8001

Study Coordinator

Role: primary

Jordan Berlin, MD

Role: primary

1-800-811-8480

Carrie Friedman, RN, BSN, OCN

Role: primary

703-636-1473

Fabricio Racca, M.D.

Role: primary

34932746100

Tatiana Hernandez Guerrero, M.D., Ph.D.

Role: primary

34915504800

Guzmán Alonso Casal, M.D.

Role: primary

34932381661

Jorge Bartolome Arcilla, M.D.

Role: primary

34913303649

Bernard Doger, M.D., Ph.D.

Role: primary

34915504800

Irene Moreno, M.D.

Role: primary

34917567825

Jose Maria Lopez Picazo, M.D.

Role: primary

34948255400

Valentina Boni, M.D.

Role: primary

34914521900

Valentina Gambardella, M.D., Ph.D.

Role: primary

34961973528

Other Identifiers

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2023-505346-26-01

Identifier Type: CTIS

Identifier Source: secondary_id

TOS-358-001

Identifier Type: -

Identifier Source: org_study_id

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