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

NCT05683418 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: TOS-358-0012023-505346-26-01
• Study Type: interventional
• Target: 241
• Locations: 2 countries
• Sites: 18

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. 1.Phase 1a: what is the maximum tolerated dose and recommended dose for phase 2?
2. 2.Phase 1a: how safe and tolerable is TOS-358 at different dose levels when taken orally once or twice per day?
3. 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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Determine the rate of dose-limiting toxicities (DLTs)

  First 21 days of treatment

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

  Start of treatment to 30 days after last dose

Secondary Outcomes (1)

• ORR and duration of tumor control

  Up to 24 months

Study Arms (3)

TOS-358 + fulvestrant

EXPERIMENTAL

TOS-358 + fulvestrant at standard dosing

Drug: TOS-358; Drug: Fulvestrant

TOS-358 + fulvestrant + CDK4/6i

EXPERIMENTAL

TOS-358 + fulvestrant + CDK4/6i

Drug: TOS-358; Drug: Fulvestrant; Drug: Palbociclib; Drug: Ribociclib

TOS-358

EXPERIMENTAL

PIK3CA covalent inhibitor

Drug: TOS-358

Interventions

TOS-358 DRUG

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

TOS-358; TOS-358 + fulvestrant; TOS-358 + fulvestrant + CDK4/6i

Fulvestrant DRUG

Intramuscular SERD at standard doses

TOS-358 + fulvestrant; TOS-358 + fulvestrant + CDK4/6i

Palbociclib DRUG

CDK4/6 inhibitor at standard doses

TOS-358 + fulvestrant + CDK4/6i

Ribociclib DRUG

CDK4/6 inhibitor at standard doses

TOS-358 + fulvestrant + CDK4/6i

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Totus Medicines: lead

Study Sites (18)

Northwestern Memorial Hospital

Chicago, Illinois, 60611, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19106, United States

RECRUITING

Sarah Cannon Cancer Center

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

Texas Oncology - Flower Mound

Flower Mound, Texas, 75028, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

NEXT Oncology - Hospital Quironsalud Barcelona - PPDS

Barcelona, 08023, Spain

RECRUITING

START Barcelona HM Nou Delfos

Barcelona, 08023, Spain

RECRUITING

Instituto de Investigacion Oncologica Vall dHebron (VHIO) - EPON

Barcelona, 08035, Spain

RECRUITING

Hospital Clinico San Carlos

Madrid, 28040, Spain

RECRUITING

START MADRID Hospital Universitario Fundacion Jimenez Diaz - EDOS

Madrid, 28050, Spain

RECRUITING

START MADRID Hospital Universitario HM Sanchinarro - CIOCC

Madrid, 28050, Spain

RECRUITING

Clinica Universidad de Navarra

Pamplona, 31008, Spain

RECRUITING

NEXT Oncology - Hospital Quironsalud Madrid - PPDS

Pozuelo de Alarcón, 28223, Spain

RECRUITING

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

RECRUITING

MeSH Terms

Conditions

Hereditary Sensory and Autonomic Neuropathies; Breast Neoplasms

Interventions

Fulvestrant; palbociclib; ribociclib

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Zelanna Goldberg, MD

  Totus Medicines

  STUDY DIRECTOR

Central Study Contacts

Clinical Trials

CONTACT

Please e-mail; clinicaltrials@totusmedicines.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 Patients with locally advanced, recurrent or metastatic HR+ HER2- breast cancer with PIK3CA mutation per local assessment will be enrolled in protocol defined groups in combination with fulvestrant +/- CDK4/6i.

Study Record Dates

• First Submitted: November 12, 2022
• First Posted: January 13, 2023
• Study Start: February 15, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (9); US (9)