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

April 8, 2024 updated by: Totus Medicines

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

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?

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

241

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope
        • Contact:
        • Principal Investigator:
          • Marwan Fakih, MD
      • Los Angeles, California, United States, 90033
        • Recruiting
        • University of Southern California, Norris Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Anthony El-Khoueiry, MD
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University, Yale Cancer Center
        • Contact:
        • Principal Investigator:
          • Patricia LoRusso, DO, PhD
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern Memorial Hospital
        • Principal Investigator:
          • Aparna Kalyan, MD
        • Contact:
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Not yet recruiting
        • University of Maryland Greenbaum Comprehensive Cancer Center
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Recruiting
        • Henry Ford Hospital
        • Contact:
        • Principal Investigator:
          • Philip Philip, MD
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Recruiting
        • University of Cincinnati Medical Center
        • Principal Investigator:
          • Davendra Sohal, MD
        • Contact:
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • University Hospitals Cleveland Medical Center
        • Principal Investigator:
          • David Bajor, MD
        • Contact:
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73104
        • Recruiting
        • Stephenson Cancer Center
        • Contact:
        • Principal Investigator:
          • Susanna Ulahannan, MD
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
    • Utah
      • West Valley City, Utah, United States, 84119
        • Recruiting
        • START- Mountain Region
        • Principal Investigator:
          • Justin Call, MD
        • Contact:
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Recruiting
        • Virginia Cancer Specialists, PC
        • Principal Investigator:
          • Alexander Spira, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: TOS-358 Single Agent Arm
Multiple doses of TOS-358 for oral administration.
Drug: TOS-358
Covalent Phosphoinositide-3-Kinase (PI3K)-alpha Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determine the rate of dose-limiting toxicities (DLTs)
Time Frame: First 21 days of treatment
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
Start of treatment to 30 days after last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Totus Medicines

Investigators

  • Study Director: Ovid Trifan, MD, PhD, Totus Medicines

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 15, 2023

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

November 12, 2022

First Submitted That Met QC Criteria

January 5, 2023

First Posted (Actual)

January 13, 2023

Study Record Updates

Last Update Posted (Actual)

April 9, 2024

Last Update Submitted That Met QC Criteria

April 8, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TOS-358-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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