Recruiting
Phase 1

TOS-358

Sponsor:

Totus Medicines

Code:

NCT05683418

Conditions

HR+/HER2-negative Breast Cancer

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

Interventions

TOS-358

Fulvestrant

Palbociclib

Ribociclib

Study Details

Brief 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)

Conditions

HR+/HER2-negative Breast Cancer

Study ID

NCT05683418

Start date

Feb 15, 2023

Status verified date

Apr, 2026

Completion date

Dec, 2027

Anticipated

Primary completion date

Dec, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

241 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: TOS-358 + fulvestrant

TOS-358 + fulvestrant at standard dosing

experimental: TOS-358 + fulvestrant + CDK4/6i

TOS-358 + fulvestrant + CDK4/6i

experimental: TOS-358

PIK3CA covalent inhibitor

Interventions

TOS-358

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

Fulvestrant

Intramuscular SERD at standard doses

Palbociclib

CDK4/6 inhibitor at standard doses

Ribociclib

CDK4/6 inhibitor at standard doses

Primary outcome measure

  • Determine the rate of dose-limiting toxicities (DLTs) [ Time Frame: 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 ]

Central Contacts and Locations

Central contacts

Clinical Trials

Please e-mailclinicaltrials@totusmedicines.com

Locations

Northwestern Memorial Hospital

Recruiting

Chicago, Illinois, United States, 60611

Contacts

Essence Baymon

312-695-9361essence.baymon@northwestern.edu

Stella Estrella

(312) 695-1102stella.estrella@northwestern.edu

Principal Investigator:

William Gradishar, MD

Beth Israel Deaconess Medical Center

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Victoria Weden

617-975-7489vweden@bidmc.harvard.edu

Gary Barahona

gbaraho1@bidmc.harvard.edu

Principal Investigator:

Gerburg Wulf, MD

Dana-Farber Cancer Institute

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Abigail Goldberg

abigail_goldberg@dfci.harvard.edu

Principal Investigator:

Antonio Giordano, MD, PhD

Comprehensive Cancer Centers of Nevada

Recruiting

Las Vegas, Nevada, United States, 89169

Contacts

AnaArlene Ramirez, RN, OCN

702-952-3406anaarlene.ramirez@usoncology.com

Eidan Gutierrez

Eidan.Gutierrez@usoncology.com

Principal Investigator:

Liawaty Ho, MD

University of Pennsylvania

Recruiting

Philadelphia, Pennsylvania, United States, 19106

Contacts

Anais Iturralde, BSN

215-829-6292Anais.Iturralde@Pennmedicine.upenn.edu

Study Coordinator

PAhemoncResearch@uphs.upenn.edu

Principal Investigator:

Mark Diamond, MD, PhD

Sarah Cannon Cancer Center

Recruiting

Nashville, Tennessee, United States, 37203

Contacts

Ethan Trull

(615) 828 - 7996ethan.trull@scri.com

Tim Duff

(615) 329-7274tim.duff@scri.com

Principal Investigator:

Erika Hamilton, MD

Vanderbilt-Ingram Cancer Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

Jordan Berlin, MD

1-800-811-8480CIP@VUMC.ORG

Principal Investigator:

Jordan Berlin, MD

Texas Oncology - Flower Mound

Recruiting

Flower Mound, Texas, United States, 75028

Contacts

Sarah Coates

(972) 537-4100sarah.coates@usoncology.com

Principal Investigator:

Vibha T Thomas, MD

Virginia Cancer Specialists

Recruiting

Fairfax, Virginia, United States, 22031

Contacts

Alexander Spira, MD

703-636-1473alexander.spira@usoncology.com

Lilliana Payne

(703) 208-9396Lilliana.Payne@usoncology.com

More Information

Sponsor

Totus Medicines

Last update posted

Apr 22, 2026

Last verified

Apr, 2026

Keywords

  • PI3K-alpha
  • breast cancer
  • metastatic breast cancer
  • PIK3CA
  • hormone receptor positive breast cancer

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Totus Medicines on 2026-04-22.