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


Totus Medicines

Status and phase

Phase 1


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


Drug: TOS-358

Study type


Funder types




Details and patient eligibility


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?

Full 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.


241 estimated patients




18+ years old


No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose




Interventional model

Single Group Assignment


None (Open label)

241 participants in 1 patient group

TOS-358 Single Agent Arm
Experimental group
Multiple doses of TOS-358 for oral administration.
Drug: TOS-358

Trial contacts and locations



Central trial contact

Clinical Trials

Data sourced from

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