TOS-358 in Adults With Select Solid Tumors

INTRODUCTION

Org Study ID: TOS-358-001
Secondary ID: N/A
NCT ID: NCT05683418
Sponsor: Totus Medicines

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?

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.

Overall Status
Recruiting
Start Date
February 15, 2023
Phase
Phase 1
Study Type
Interventional

Primary Outcome 1 - Measure:

Primary Outcome 1 - Timeframe: N/A

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

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.

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Name: Ovid Trifan, MD, PhD

Role: Study Director

Affiliation: Totus Medicines

Name: Clinical Trials

Phone: Please e-mail

Email: clinicaltrials@totusmedicines.com

Facility	Status	Contact
Facility: City of Hope Duarte, California 91010 United States	Status: Recruiting	Contact: Contact Marwan Fakih, MD 626-256-4673 mfakih@coh.org Principal Investigator Marwan Fakih, MD
Facility: University of Southern California, Norris Comprehensive Cancer Center Los Angeles, California 90033 United States	Status: Recruiting	Contact: Contact Xiomara Menendez, RN Xiomara.Menendez@med.usc.edu Principal Investigator Anthony El-Khoueiry, MD
Facility: Yale University, Yale Cancer Center New Haven, Connecticut 06520 United States	Status: Recruiting	Contact: Contact Ingid Palma 203-833-1034 ingrid.palma@yale.edu Principal Investigator Patricia LoRusso, DO, PhD
Facility: Northwestern Memorial Hospital Chicago, Illinois 60611 United States	Status: Recruiting	Contact: Contact Study Coordinator 312-695-1301 cancer@northwestern.edu Principal Investigator Aparna Kalyan, MD
Facility: Henry Ford Hospital Detroit, Michigan 48202 United States	Status: Recruiting	Contact: Contact Huzaifa Hussain 313-874-7524 hhussai2@hfhs.org Principal Investigator Philip Philip, MD
Facility: University of Cincinnati Medical Center Cincinnati, Ohio 45219 United States	Status: Recruiting	Contact: Contact Davendra Sohal, MD 513-558-2361 sohalda@ucmail.uc.edu Principal Investigator Davendra Sohal, MD
Facility: University Hospitals Cleveland Medical Center Cleveland, Ohio 44106 United States	Status: Recruiting	Contact: Contact David Bajor, MD David.Bajor@Uhhospitals.org Principal Investigator David Bajor, MD
Facility: Stephenson Cancer Center Oklahoma City, Oklahoma 73104 United States	Status: Recruiting	Contact: Contact Christina Caldwell, LPN 405-271-8001 Christina-Caldwell@ouhsc.edu Principal Investigator Susanna Ulahannan, MD
Facility: University of Pennsylvania Philadelphia, Pennsylvania 19104 United States	Status: Recruiting	Contact: Contact Study Coordinator PAhemoncResearch@uphs.upenn.edu Principal Investigator Thomas Karasic, MD
Facility: START- Mountain Region West Valley City, Utah 84119 United States	Status: Recruiting	Contact: Contact Marie Asay 801-907-4770 marie.asay@startthecure.com Principal Investigator Justin Call, MD
Facility: Virginia Cancer Specialists, PC Fairfax, Virginia 22031 United States	Status: Recruiting	Contact: Contact Carrie Friedman, RN, BSC, OCN 703-636-1473 carrie.friedman@usoncology.com Principal Investigator Alexander Spira, MD

Brief Title: TOS-358 in Adults With Select Solid Tumors

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

INTRODUCTION

BRIEF SUMMARY

DETAILED DESCRIPTION

PRIMARY OUTCOMES

CONDITION

ELIGIBILITY

OFFICIAL INFORMATION

Overall Contact

LOCATION

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