TOS-358 for Cancer

Recruiting at 25 trial locations

Overseen By Clinical Trials

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Totus Medicines

Must be taking: Fulvestrant

Must not be taking: PI3K inhibitors

Disqualifiers: Diabetes, Cushing syndrome, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

241 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial evaluates the safety of a new treatment called TOS-358 in people with certain types of cancer. Researchers aim to determine the maximum safe dosage and assess how well participants tolerate taking it orally once or twice a day. They seek participants with advanced breast, head and neck, bladder, or uterine cancer who have a specific genetic marker (PIK3CA mutation) and have undergone no more than three previous treatments for metastatic disease. The trial aims to identify the optimal dose for future studies. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot have had recent systemic anticancer treatment before starting, except for breast cancer patients on fulvestrant. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that TOS-358 is likely to be safe for humans?

Research shows that TOS-358 is a new treatment being tested for safety in people with solid tumors. So far, TOS-358 has shown promise as a targeted therapy by blocking a protein called PI3Kα, which aids cancer growth.

As this is an early trial, the main goal is to assess the safety of TOS-358 for people. The trial will test different doses to determine the safest amount for future studies. Researchers are still learning about its tolerability and potential side effects.

Since TOS-358 is new and still in early testing, limited safety data exists. However, early studies are crucial for understanding if TOS-358 is safe and how it might help treat cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about TOS-358 because it targets cancer cells in a novel way by acting on specific pathways that are not the main focus of current treatments like chemotherapy or radiation. Unlike traditional options that often affect both healthy and cancerous cells, TOS-358 is designed to home in on cancer cells more precisely, potentially leading to fewer side effects and improved effectiveness. Additionally, being an oral medication makes TOS-358 more convenient compared to some existing treatments that require intravenous administration, offering patients an easier and potentially less invasive option.

What evidence suggests that TOS-358 might be an effective treatment for cancer?

Research has shown that TOS-358 holds promise for treating certain solid tumors. Early studies found that TOS-358, a drug targeting a cellular component that aids cancer growth, can combat tumors even at low doses. In these studies, TOS-358 effectively reached and impacted the target cellular component 95% of the time. Importantly, these studies also showed early signs of the drug's efficacy against tumors and did not identify any severe side effects at the tested doses. This evidence suggests that TOS-358 could become a valuable option for treating certain cancers in the future. ^{1 2 3 6 7}

Who Is on the Research Team?

Zelanna Goldberg, MD

Principal Investigator

Totus Medicines

Are You a Good Fit for This Trial?

Adults over 18 with certain advanced solid tumors and specific genetic changes (PIK3CA mutations/amplifications) can join. They should have a life expectancy of at least 3 months, be able to consent, have measurable disease, good performance status (ECOG 0 or 1), and proper organ function. Excluded are those with diabetes, obesity (BMI ≥30), recent cancer treatments, heart issues within the past six months, prior PI3K pathway inhibitors use (except some breast cancer patients), other recent cancers or active brain metastases.

Inclusion Criteria

Willing and able to provide written informed consent for this study

Measurable disease by RECIST 1.1

Life expectancy ≥ 3 months, as determined by the investigator

Exclusion Criteria

I haven't had cancer in the last 3 years, except for specific minor cases.

Body mass index (BMI) ≥ 30

I have not taken drugs targeting the PI3K-AKT-mTOR pathway, except if I have breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Finding

TOS-358 is evaluated at multiple dose levels to determine the maximum tolerated dose and recommended phase 2 dose

Until disease progression or unacceptable toxicity

Dose Expansion

Evaluate safety and tolerability in tumor-specific cohorts at the recommended phase 2 dose

Until disease progression or unacceptable toxicity

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TOS-358

Trial Overview TOS-358 is being tested for safety in adults with select solid tumors. The study will determine the highest dose patients can tolerate when taken orally once or twice daily without severe side effects and establish a recommended dose for future studies.

How Is the Trial Designed?

Group I: TOS-358 Single Agent Arm Experimental Treatment 1 Intervention

Multiple doses of TOS-358 for oral administration.

Who Is Running the Clinical Trial?

Totus Medicines

Lead Sponsor

Trials

1

Recruited

240+

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02211-7/fulltext

625P Initial results from the phase I, first-in-human study of ... Conclusions. Phase 1a data support covalent inhibition of PI3Kα using TOS-358 as a promising therapeutic that can achieve anti-tumor effects at low doses with ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05683418

A Study to Evaluate the Safety and Tolerability of TOS-358 ... 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.

3. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/totus-medicines-announces-successful-phase-1-tos-358-trial-appoints-new-cmo/

Totus Medicines Announces Successful Phase 1 Tos-358 ... The Phase 1 study showed promising results, including 95% target engagement, early signs of clinical activity, and no high-grade toxicities at ...

4. targetedonc.com targetedonc.com/view/phase-1-trial-of-tos-358-for-pi3k--mutated-tumors-begins-dosing

Phase 1 Trial of TOS-358 for PI3Kα-Mutated Tumors ... "TOS-358 represents a promising new approach to the treatment of the root cause of nearly 15% of all cancers, and we are excited to be able to ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02211-7/pdf

inhibitor TOS-358 in patients with We report long-term efficacy and safety data in adult and paediatric pts with non-primary. CNS TRK fusion cancer. Methods: Data were pooled from ...

6. aacrjournals.org aacrjournals.org/cancerres/article/83/7_Supplement/4946/724920/Abstract-4946-TOS-358-a-first-in-class-covalent

Abstract 4946: TOS-358, a first-in-class covalent PI3Kα ... TOS-358 is a highly selective first-in-class covalent inhibitor of PI3Kα and is currently in clinical development in multiple solid malignancies.

7. vicc.org vicc.org/clinical-trials/protocol-viccdtphi23103

A Study to Evaluate the Safety and Tolerability of TOS-358 ... 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.