A Study to Evaluate the Safety and Tolerability of TOS-358 in Adults With Select Solid Tumors

Colorectal Cancer Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05683418
• Other study ID #: TOS-358-001
• Status: Recruiting
• Phase: Phase 1
• Start date: February 15, 2023
• Est. completion date: December 2025

Study information

• Verified date: June 2024
• Source: Totus Medicines
• Contact: Clinical Trials
• Phone: Please e-mail
• Email: clinicaltrials[@]totusmedicines.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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?

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.

Adult subjects with histologically confirmed diagnosis of colorectal cancer, gastric cancer, non-small cell lung cancer, human epidermal growth factor receptor 2 (HER2) negative breast cancer, squamous cell carcinoma of the head and neck, urothelial cancer, or select gynecologic cancers (ovarian cancer, cervical cancer, or endometrial cancer) with known PIK3CA mutations or amplifications (as determined at a College of American Pathologists/clinical laboratory improvement amendments [CAP/CLIA]-certified or equivalently accredited diagnostic laboratory using a validated test), who meet all of the eligibility criteria will be enrolled in the Phase 1 portion of 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 241
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria

• Locally advanced, recurrent, or metastatic, incurable (any number of previous lines of therapy is allowed), histologically or cytologically confirmed: colorectal cancer; gastric cancer; non-small cell lung cancer; HER2- breast cancer; squamous cell carcinoma of the head and neck; urothelial cancer; or select gynecologic cancer (ovarian cancer, cervical cancer, or endometrial cancer)

• 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 = 3 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 < 126 mg/dL AND hemoglobin A1c (HbA1c) < 5.7%

• Available archived or fresh tumor tissue sample for detection of PIK3CA mutation by central laboratory test

Key Exclusion Criteria

• Recent systemic anticancer treatment prior to start of treatment

• Prior treatment with any PI3K, AKT, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K-AKT-mTOR pathway, except for patients with breast cancer

• Second malignancy (solid or hematologic) within the past 3 years except: Adequately treated basal cell or squamous cell skin cancer; carcinoma in situ of the cervix, or prostate cancer with Gleason score < 6 and undetectable prostate specific antigen over 12 months ;ductal breast carcinoma in situ with full surgical resection (ie, negative margins); treated medullary or papillary thyroid cancer; metaplastic breast cancer

• History of diabetes of any type

• Body mass index (BMI) = 30

• Cushing syndrome

• Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to the first dose of investigational product

• Known active central nervous system (CNS) metastases.

Related Conditions & MeSH terms

• Carcinoma
• Cervical Cancer
• Colorectal Cancer
• Endometrial Cancer
• Endometrial Neoplasms
• Gastric Cancer
• HER2-negative Breast Cancer
• Non-small Cell Lung Cancer
• Ovarian Cancer
• Squamous Cell Carcinoma of Head and Neck
• Urothelial Carcinoma

Intervention

Drug:
• TOS-358
Covalent Phosphoinositide-3-Kinase (PI3K)-alpha Inhibitor

Locations

Country	Name	City	State
United States	University of Maryland Greenbaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Northwestern Memorial Hospital	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	University of Southern California, Norris Comprehensive Cancer Center	Los Angeles	California
United States	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee
United States	Yale University, Yale Cancer Center	New Haven	Connecticut
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	START- Mountain Region	West Valley City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Totus Medicines

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the rate of dose-limiting toxicities (DLTs)		First 21 days of treatment
Primary	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