Zipalertinib for Lung Cancer

(REZILIENT4 Trial)

Recruiting at 207 trial locations

Overseen By Taiho Oncology INC

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Taiho Oncology, Inc.

Must not be taking: EGFR inhibitors, CYP3A4 inducers

Disqualifiers: ILD, Cardiac disease, Other cancer, others

Stay on Your Current Meds You can continue your current medications while participating

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21-day cycles, duration varies until treatment discontinuation criteria are met

360 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the new drug zipalertinib, combined with standard chemotherapy, is more effective than a placebo in treating early-stage non-small cell lung cancer (NSCLC) after surgery. It specifically targets patients with a rare mutation in the EGFR gene, which influences cell growth. Individuals who recently underwent surgery to remove lung cancer and have one of these uncommon gene mutations might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants the opportunity to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial requires you to stop taking any medications that are strong or moderate cytochrome p450 (CYP) 3A4 inducers or inhibitors at least 7 days before starting the study treatment. It's best to discuss your current medications with the study team to see if any need to be adjusted.

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, most patients taking zipalertinib experienced mild to moderate side effects. Few patients needed to lower their dose or stop the treatment due to side effects, allowing most to continue as prescribed. This suggests that zipalertinib is usually well-tolerated. However, individual experiences may vary, so discussing any concerns with a doctor is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Zipalertinib is unique because it targets specific genetic mutations associated with lung cancer, potentially offering a more personalized treatment approach. Unlike traditional chemotherapy, which attacks rapidly dividing cells indiscriminately, zipalertinib is designed to hone in on cancer cells, potentially reducing side effects and improving outcomes. Researchers are excited about this treatment because it combines with standard chemotherapy regimens initially and then continues as a monotherapy, which could enhance its effectiveness while maintaining manageable side effects.

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

Research has shown that zipalertinib yields promising results for treating non-small cell lung cancer (NSCLC) with rare EGFR mutations. In studies, it proved effective and had manageable side effects. Patients with the specific EGFR ex20ins mutation in NSCLC experienced clinical benefits. In this trial, participants will receive either zipalertinib or a placebo, both combined with adjuvant platinum-based chemotherapy. The treatment also resulted in low rates of dose changes or discontinuation due to side effects. These findings suggest that zipalertinib could be a helpful option for people with certain types of lung cancer. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for adults with early-stage (IB-IIIA) non-small cell lung cancer (NSCLC), who've had complete tumor removal surgery and recovered. They must have a specific uncommon EGFR mutation, be in good physical condition (ECOG PS 0 or 1), and have enough archived tumor tissue for testing.

Inclusion Criteria

My lung cancer is confirmed and mostly not squamous type.

I have had or will have a brain MRI or CT scan before surgery or randomization.

My lung cancer was completely removed by surgery with no cancer left at the edges.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjuvant platinum-based chemotherapy in combination with zipalertinib or placebo, followed by monotherapy with zipalertinib or placebo

21-day cycles, duration varies until treatment discontinuation criteria are met

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Zipalertinib

Trial Overview The study tests the effectiveness of Zipalertinib combined with adjuvant chemotherapy against a placebo plus chemotherapy in patients with resected NSCLC that has an uncommon EGFR mutation. It aims to see if Zipalertinib can prevent cancer from returning.

How Is the Trial Designed?

Group I: Zipalertinib Experimental Treatment 4 Interventions

Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin 75 milligrams per square meter (mg/m\^2) or carboplatin (area under concentration \[AUC\] 5 milligrams per milliliter per minute mg/mL/min) plus pemetrexed 500 mg/m\^2, administered via intravenous (IV) infusion, on 21-day cycle, in combination with zipalertinib 100 mg, orally, twice daily (BID). After completion of chemotherapy, participants will continue on zipalertinib monotherapy 100 mg, orally, BID on 21-day cycle, until the participant meets any of the treatment discontinuation criteria.

Group II: Placebo Placebo Group 4 Interventions

Participants will receive adjuvant platinum-based chemotherapy consisting of cisplatin 75 mg/m\^2 or carboplatin AUC 5 mg/mL/min plus pemetrexed 500 mg/m\^2, administered via IV infusion, on 21-day cycle, in combination with zipalertinib matching-placebo 100 mg, orally, BID. After completion of chemotherapy, participants will continue on zipalertinib matching-placebo monotherapy 100mg, orally, BID on 21-day cycle, until the participant meets any of the treatment discontinuation criteria.

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. onclive.com onclive.com/view/zipalertinib-shows-early-efficacy-with-manageable-safety-in-egfr-mutant-nsclc-with-cns-or-leptomeningeal-disease

Zipalertinib Shows Early Efficacy With Manageable Safety ... Zipalertinib demonstrated preliminary efficacy and low rates of treatment-related dose reductions and discontinuations in NSCLC harboring EGFR ...

5. lungcancerstoday.com lungcancerstoday.com/post/rezilient2-trial-zipalertinib-shows-preliminary-clinical-efficacy-in-patients-with-uncommon-egfr-mutations

REZILIENT2 Trial: Zipalertinib Shows 'Preliminary Clinical ... Zipalertinib showed “preliminary clinical efficacy” as a treatment for patients with non–small cell lung cancer (NSCLC) who harbor uncommon, ...

6. 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.