TAS3351 for Non-Small Cell Lung Cancer

(TAS3351 Trial)

No longer recruiting at 25 trial locations

Overseen By Taiho Oncology, Inc

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Taiho Oncology, Inc.

Disqualifiers: CNS metastases, Cardiac condition, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a new treatment, TAS3351, for individuals with advanced or metastatic non-small cell lung cancer (NSCLC) that has a specific mutation in the cancer's DNA. The trial consists of three parts: initially, it tests various doses to determine the optimal one; then it expands to include more participants to assess the treatment's effects; and finally, it further evaluates the treatment's effectiveness. Suitable candidates have NSCLC that is inoperable and contains a C797S mutation in the EGFR gene. As a Phase 1 and Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that TAS3351 is likely to be safe for humans?

Research shows that TAS3351 is a promising new treatment being tested for safety in people with advanced non-small cell lung cancer (NSCLC) who have a specific gene change called the C797S EGFR mutation. Since this is the first time TAS3351 is tested in humans, existing data is limited. However, researchers closely monitor how well people handle TAS3351 and what side effects might occur.

In studies like this, safety is the top priority. The study adjusts the dosage to find the safest and most effective amount for people to take. While specific data on side effects or tolerance is not yet available, the early phase of the trial indicates that researchers are still collecting important safety information.

It's important to know that TAS3351 is not yet approved for any use, so its safety profile is still being developed through this ongoing research. Trial participants will be closely monitored to ensure their safety and to gather more data on how TAS3351 affects them. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for non-small cell lung cancer?

Unlike the standard treatments for non-small cell lung cancer, which often involve chemotherapy, immunotherapy, or targeted therapies like EGFR inhibitors, TAS3351 acts on a specific mutation known as C797S EGFRmt. This mutation can make cancer resistant to current EGFR-targeted drugs, but TAS3351 aims to overcome this resistance by targeting it directly. Researchers are excited about TAS3351 because it represents a new approach, potentially offering more effective treatment for patients with this difficult-to-treat mutation.

What evidence suggests that TAS3351 might be an effective treatment for non-small cell lung cancer?

Research has shown that TAS3351 is a promising treatment for non-small cell lung cancer (NSCLC) with a specific change known as the C797S EGFR mutation. This mutation often causes resistance to current treatments. TAS3351, a new type of drug called a tyrosine kinase inhibitor (TKI), targets certain proteins in cancer cells to halt their growth. Notably, TAS3351 can reach the brain, potentially benefiting patients whose cancer has spread there. While researchers continue to gather information about TAS3351, it is designed to target resistance mutations, suggesting it could succeed where other treatments fail. Participants in this trial will receive TAS3351 in different phases to evaluate its safety and efficacy. ^{1 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with advanced or metastatic non-small cell lung cancer (NSCLC) who have a specific mutation called C797S in the EGFR gene. Participants must be able to perform daily activities with little to no assistance (ECOG performance status of 0 or 1), have tumor tissue available for analysis, and their major organs must function well. They should not be part of other conflicting studies, have unstable brain metastases, unresolved effects from past cancer treatments, significant heart issues, or conditions preventing pill ingestion.

Inclusion Criteria

My lung cancer cannot be removed by surgery and has spread.

You need to have a way for the doctors to measure your disease.

My organs are working well.

Exclusion Criteria

Are a pregnant or breastfeeding female

I have a serious heart condition.

I cannot swallow or digest pills.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Dose escalation will assess the safety and determine the recommended phase 2 dose and regimen of TAS3351 administered orally

21 days per cycle, estimated 20 months

Dose Expansion

The dose expansion part will explore the efficacy of TAS3351 in NSCLC patients with C797S EGFR mutations

estimated 9 months

Phase 2

The phase 2 part will assess the efficacy of TAS3351 in NSCLC patients with C797S EGFR mutations

estimated 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TAS3351

Trial Overview

The study is testing TAS3351's safety and effectiveness when taken orally by patients with NSCLC that has an acquired C797S EGFR mutation. It's a first-in-human study divided into phases: initial dose escalation to find the right dosage followed by expansion and phase II trials focusing on those who meet specific genetic criteria.

How Is the Trial Designed?

Group I: TAS3351 Part C (Phase 2) Experimental Treatment 1 Intervention

To assess efficacy of TAS3351 in NSCLC patients with C797S EGFRmt. TAS3351 will be administered at the recommended phase 2 dose.

Group II: TAS3351 Part B (Dose Expansion) Experimental Treatment 1 Intervention

TAS3351 in NSCLC patients with C797S EGFRmt. TAS3351 will be administered at the recommended phase 2 dose determined in Part A.

Group III: TAS3351 Part A (Dose Escalation) Experimental Treatment 1 Intervention

Dose escalation will assess the safety and determine the recommended phase 2 dose and regimen of TAS3351 administered orally.

Who Is Running the Clinical Trial?

Taiho Oncology, Inc.

Lead Sponsor

Trials

79

Recruited

12,700+

Tim Whitten

Taiho Oncology, Inc.

Chief Executive Officer since 2018

MBA and Pharmacy degree

Harold Keer

Taiho Oncology, Inc.

Chief Medical Officer

MD, PhD

Published Research Related to This Trial

Recent advances in molecular characterization of lung cancer have led to the development of new targeted therapies for various oncogenic alterations, with 62 clinical trials assessing these novel agents.

The FDA has approved seven new targeted treatments for specific mutations in advanced non-small cell lung cancer (NSCLC), indicating significant progress in improving patient outcomes based on their unique molecular profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The rapidly evolving landscape of novel targeted therapies in advanced non-small cell lung cancer. Melosky, B., Wheatley-Price, P., Juergens, RA., et al.[2021]

Recent advancements in precision medicine, particularly through next-generation sequencing, have transformed the treatment of advanced non-small cell lung cancer (NSCLC) by enabling targeted therapies and immunotherapy, leading to improved survival rates.

The shift from traditional chemotherapy to targeted treatments and immune checkpoint inhibitors (ICIs) has not only enhanced efficacy but also reduced toxicity for patients with metastatic lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paradigm shift in the management of metastatic nonsmall cell lung cancer. Gupta, R., Smalley, M., Anusim, N., et al.[2021]

In a phase 2 study involving 18 patients with small cell lung cancer, TAS-102 did not demonstrate significant efficacy compared to standard treatments, leading to early termination of the trial due to futility.

Patients receiving TAS-102 had a median progression-free survival of only 1.4 months, significantly shorter than the 2.7 months observed in the control group, indicating that TAS-102 is not an effective second-line treatment for this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 randomized study of TAS-102 versus topotecan or amrubicin in patients requiring second-line chemotherapy for small cell lung cancer refractory or sensitive to frontline platinum-based chemotherapy. Scagliotti, G., Nishio, M., Satouchi, M., et al.[2020]

The repository includes 79 patient-derived xenograft (PDX) models of lung cancer, primarily non-small cell lung cancer (NSCLC), which have been thoroughly characterized for their genomic and clinical features, making them a valuable resource for testing new cancer therapies.

These PDX models maintain key characteristics of the original patient tumors and demonstrate expected treatment responses, confirming their utility as reliable preclinical platforms for cancer research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Genomically and Clinically Annotated Patient-Derived Xenograft Resource for Preclinical Research in Non-Small Cell Lung Cancer. Woo, XY., Srivastava, A., Mack, PC., et al.[2022]

Current standard treatment for advanced non-small-cell lung cancer involves doublet chemotherapy, which has shown 1-year survival rates of approximately 35% and 2-year survival rates of about 15%.

Preliminary studies indicate that triplet therapy may enhance survival rates compared to double therapy, with toxicity rates being low enough to support the development of these three-drug combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triplet combination chemotherapy and targeted therapy regimens. Bunn, PA.[2005]

Citations

1.

clinicaltrials.eu

clinicaltrials.eu/inn/tas3351/

Tas3351 – Application in Therapy and Current Clinical ...

A groundbreaking clinical trial is underway to evaluate the safety and effectiveness of TAS3351, a novel oral medication for patients with advanced non-small ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10605462/

New Generations of Tyrosine Kinase Inhibitors in Treating ...

Newer generations of TKIs have better results in controlling the disease and extending patient survival. These drugs also work better in the brain.

3.

researchgate.net

researchgate.net/publication/391996693_Discovery_of_TAS3351_a_brain-penetrable_fourth-generation_EGFR-TKI_that_overcomes_T790M_and_C797S_resistance_mutations

(PDF) Discovery of TAS3351, a brain-penetrable fourth- ...

These findings indicate that TAS3351 is a promising therapeutic candidate for patients with NSCLC who have relapsed and are refractory to ...

4.

withpower.com

withpower.com/trial/phase-2-lung-neoplasms-2-2023-aa08f

TAS3351 for Non-Small Cell Lung Cancer

Current standard treatment for advanced non-small-cell lung cancer involves doublet chemotherapy, which has shown 1-year survival rates of approximately 35% and ...

5.

centerwatch.com

centerwatch.com/clinical-trials/listings/NCT05765734/a-study-of-tas3351-in-nsclc-patients-with-egfrmt

A Study of TAS3351 in NSCLC Patients With EGFRmt

This is a first-in-human, open label, Phase 1/2 study to investigate the safety and efficacy of TAS3351 in patients with advanced or ...

6.

trialx.com

trialx.com/clinical-trials/listings/249557/a-study-of-tas3351-in-nsclc-patients-with-egfrmt/

A Study of TAS3351 in NSCLC Patients With EGFRmt

This is a first-in-human, open label, Phase 1/2 study to investigate the safety and efficacy of TAS3351 in patients with advanced or metastatic non-small cell ...

7.

aacrjournals.org

aacrjournals.org/cancerres/article/82/12_Supplement/3259/703329/Abstract-3259-TAS3351-is-a-4th-generation-EGFR-TKI

Abstract 3259: TAS3351 is a 4th-generation EGFR-TKI ...

Here, we report TAS3351 as a novel, next-generation EGFR-TKI designed to overcome C797S and T790M-mediated resistance in NSCLC patients. Methods ...

8.

app.trialscreen.org

app.trialscreen.org/trials/phase-1-2-non-small-cell-lung-cancer-tas3351-nsclc-patients-egfrmt-trial-nct05765734

A Study of TAS3351 in NSCLC Patients With EGFRmt

This study aims to evaluate the safety and effectiveness of TAS3351, an investigational drug, in treating non-small cell lung cancer patients who have a ...