TAS3351 for Non-Small Cell Lung Cancer

(TAS3351 Trial)

Recruiting at 17 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

200 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called TAS3351 to see if it is safe and effective for patients with advanced lung cancer that has a specific genetic mutation. The drug works by blocking a protein that helps cancer cells grow.

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.

What makes the drug TAS3351 unique for treating non-small cell lung cancer?

TAS3351 is unique because it is an oral combination treatment that includes trifluridine, a thymidine-based nucleoside analog, and tipiracil hydrochloride, which has shown greater activity than cisplatin in small cell lung cancer models. This suggests it may offer a novel approach compared to traditional chemotherapy and targeted therapies for non-small cell lung cancer. ^{1 2 3 4 5}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Triplet combination chemotherapy and targeted therapy regimens. [2005]

2. Ireland 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. [2020]

3. Ireland pubmed.ncbi.nlm.nih.gov

The rapidly evolving landscape of novel targeted therapies in advanced non-small cell lung cancer. [2021]

4. India pubmed.ncbi.nlm.nih.gov

Paradigm shift in the management of metastatic nonsmall cell lung cancer. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

A Genomically and Clinically Annotated Patient-Derived Xenograft Resource for Preclinical Research in Non-Small Cell Lung Cancer. [2022]