Zipalertinib for Non-Small Cell Lung Cancer

(REZILIENT2 Trial)

Recruiting at 177 trial locations

Overseen By Taiho Oncology, INC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Taiho Oncology, Inc.

Must not be taking: CYP3A4 inducers, inhibitors

Disqualifiers: Uncontrolled seizures, Cardiac disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Until progression or withdrawal

224 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of the drug zipalertinib for individuals with advanced Non-Small Cell Lung Cancer (NSCLC) that has specific genetic changes, known as EGFR mutations. Participants will take zipalertinib in pill form, and researchers will monitor how the body processes the drug and its impact on cancer control. The trial includes several groups testing different scenarios, such as the presence of brain metastases or prior treatments. Individuals with NSCLC who have specific genetic mutations and have experienced disease progression or have not yet received treatment may be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking any medications that are strong or moderate CYP3A4 inducers or inhibitors at least 7 days before starting the study treatment. If you're on such medications, you may need to discuss alternatives with your doctor.

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

Research has shown that zipalertinib is generally safe for people with non-small cell lung cancer (NSCLC). In earlier studies, zipalertinib demonstrated a manageable safety profile. While some side effects might occur, they are usually not serious and doctors can handle them. These studies focused on patients with specific genetic changes, such as EGFR ex20ins, and found encouraging safety results. Discussing possible side effects with a doctor is important to understand what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Non-Small Cell Lung Cancer?

Researchers are excited about zipalertinib because it offers a novel approach to treating non-small cell lung cancer (NSCLC). Unlike standard treatments, which often involve chemotherapy or existing targeted therapies like EGFR inhibitors, zipalertinib targets uncommon EGFR mutations and shows potential efficacy in challenging cases like active brain metastases. Additionally, it is administered orally, which can be more convenient for patients. This fresh mechanism of action and delivery method could provide new hope for those who haven't responded well to other treatments.

What evidence suggests that zipalertinib could be an effective treatment for Non-Small Cell Lung Cancer?

Research has shown that zipalertinib could be a promising treatment for non-small cell lung cancer (NSCLC) with specific EGFR gene changes. In previous studies, patients with these gene changes, who had already tried other treatments, experienced significant benefits from zipalertinib. The treatment proved effective and had manageable side effects, allowing patients to improve without severe issues. In this trial, participants will be divided into different cohorts to receive zipalertinib, including those receiving it as a first-line treatment, those with active brain metastases, and those with other uncommon EGFR mutations. These encouraging results suggest that zipalertinib could be a hopeful option for people with these specific genetic types of NSCLC. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults with advanced non-small cell lung cancer (NSCLC) that have specific mutations called EGFR exon 20 insertions or other uncommon mutations. Participants must not have had prior systemic therapy for advanced disease, except in certain cohorts where progression after such therapies is required. They should be able to perform daily activities with minimal assistance and agree to use birth control. People with recent COVID-19, significant heart issues, another primary malignancy within the last two years, or who are pregnant can't join.

Inclusion Criteria

I can provide samples of my tumor for research.

I am at least 18 years old or considered an adult by my country's laws.

I have brain metastases.

Exclusion Criteria

I had chest radiation therapy less than 28 days ago or palliative radiation less than 14 days ago.

I haven't had cancer immunotherapy in the last 28 days.

I have taken Zipalertinib (TAS6417/CLN081) before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive zipalertinib orally twice a day (BID) continuously until documentation of progression or withdrawal criteria are met

Until progression or withdrawal

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Zipalertinib

Trial Overview The study tests Zipalertinib's safety and effectiveness on patients with NSCLC harboring specific genetic changes. It involves different patient groups based on their treatment history and mutation type, assessing how well they respond to this new drug and monitoring any improvements in their condition.

How Is the Trial Designed?

Group I: DDI Substudy: Transporter Cocktail Group Experimental Treatment 2 Interventions

Participants will receive a single dose of transporter probe substrates (Transporter cocktail) alone prior to the start of zipalertinib dosing and a single dose of Transporter cocktail in combination with zipalertinib at steady state. Zipalertinib will be dosed, orally BID in Cycle 1 (cycle length = 21 days), followed by continuous treatment with zipalertinib until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Group II: DDI Substudy: CYP Cocktail Group Experimental Treatment 2 Interventions

Participants will receive a single dose of CYP enzyme probe substrates (CYP cocktail) alone prior to the start of zipalertinib dosing and a single dose of CYP cocktail in combination with zipalertinib at steady state. Zipalertinib will be dosed, orally BID in Cycle 1 (cycle length = 21 days), followed by continuous treatment with zipalertinib until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Group III: Cohort D ("other uncommon EGFRmts"). Experimental Treatment 1 Intervention

Cohort D participants will receive zipalertinib orally, BID continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Group IV: Cohort C ("active brain mets") Experimental Treatment 1 Intervention

Cohort C participants will receive zipalertinib orally, BID continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Group V: Cohort B ("first-line treatment") Experimental Treatment 1 Intervention

Cohort B participants will receive zipalertinib orally, BID continuously until documentation of PD or until other withdrawal criteria are met, whichever comes first.

Group VI: Cohort A ("prior ex20ins treatment") Experimental Treatment 1 Intervention

Cohort A ("prior ex20ins treatment") participants will receive zipalertinib orally twice a day (BID) continuously until documentation of progressive disease (PD) or until other withdrawal criteria are met, whichever comes first.

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

Citations

1. taihooncology.com taihooncology.com/us/news/taiho-oncology-and-cullinan-therapeutics-present-data-on-zipalertinib-at-the-iaslc-2025-world-conference-on-lung-cancer/

Taiho Oncology and Cullinan Therapeutics Present Data ... Updated efficacy and safety data to be presented from the REZILIENT1 trial of zipalertinib from the cohort of patients with non-small cell ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00763

Zipalertinib in Patients With Epidermal Growth Factor ... Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with EGFR ex20ins-mutant NSCLC who received prior ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40450572/

Zipalertinib in Patients With Epidermal Growth Factor ... Conclusion: Zipalertinib demonstrated clinically meaningful efficacy with a manageable safety profile in patients with EGFR ex20ins-mutant NSCLC ...

4. prnewswire.com prnewswire.com/news-releases/taiho-oncology-and-cullinan-therapeutics-present-data-on-zipalertinib-at-the-iaslc-2025-world-conference-on-lung-cancer-302549926.html

Taiho Oncology and Cullinan Therapeutics Present Data ... Updated efficacy and safety data to be presented from the REZILIENT1 trial of zipalertinib from the cohort of patients with non-small cell ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05967689

NCT05967689 | A Study of Zipalertinib in Patients With ... This study will evaluate the safety and efficacy of zipalertinib in participants with locally advanced or metastatic NSCLC harboring EGFR ex20ins mutations.