Zipalertinib + Chemotherapy for Non-Small Cell Lung Cancer
(REZILIENT3 Trial)
Recruiting in Palo Alto (17 mi)
+113 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Taiho Oncology, Inc.
Must not be taking: CYP3A4 inducers/inhibitors
Disqualifiers: Cardiac disease, Interstitial lung disease, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Trial Summary
What is the purpose of this trial?
The purpose of this study is to evaluate the safety and efficacy of zipalertinib in combination with standard first-line platinum-based chemotherapy compared to chemotherapy alone, in patients with locally advanced or metastatic NSCLC with EGFR ex20ins mutations.
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications, but you cannot take medications that strongly affect CYP3A4 enzymes within 7 days before starting the trial. It's best to discuss your current medications with the trial team.
What data supports the effectiveness of the drug Zipalertinib + Chemotherapy for Non-Small Cell Lung Cancer?
What makes the drug Zipalertinib unique for treating non-small cell lung cancer?
Zipalertinib is a novel treatment option for non-small cell lung cancer that targets specific genetic mutations in cancer cells, potentially offering a more personalized approach compared to traditional chemotherapy. This drug is designed to inhibit certain proteins that help cancer cells grow, making it different from standard treatments that do not target these specific mutations.14678
Research Team
Eligibility Criteria
Adults with advanced non-small cell lung cancer (NSCLC) that have a specific mutation called EGFR exon 20 insertion. They must be over 18, have stable brain metastases if present, an ECOG performance status of 0 or 1, and a life expectancy of at least three months. Participants should not have had prior systemic treatment for their NSCLC except certain adjuvant/neoadjuvant therapies over six months ago.Inclusion Criteria
I have at least one tumor that can be measured if I'm enrolling in Part B.
I haven't had systemic treatment for my advanced non-squamous NSCLC, but early-stage treatments over 6 months ago are okay.
I can provide a sample of my tumor for testing.
See 10 more
Exclusion Criteria
I had cancer before, but it's either been treated or stable for over 2 years.
I haven't had certain treatments or major surgery within the last month.
I have serious heart problems, including heart failure or irregular heartbeat.
See 11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Safety Lead-In
Determine the recommended dose of zipalertinib in combination with standard chemotherapy
21 days per cycle, until progressive disease or withdrawal
Rolling-6 design, multiple visits
Phase 3 Treatment
Randomized, controlled, open-label study to assess efficacy and safety of zipalertinib with chemotherapy
21 days per cycle, carboplatin or cisplatin for 4 cycles, until progressive disease or withdrawal
Multiple visits per cycle
Follow-up
Participants are monitored for safety and effectiveness after treatment
Approximately 5 years
Treatment Details
Interventions
- Zipalertinib (Tyrosine Kinase Inhibitor)
Trial OverviewThe trial is testing the effectiveness and safety of a new drug named Zipalertinib in combination with standard platinum-based chemotherapy versus chemotherapy alone in patients with advanced NSCLC harboring the EGFR exon 20 insertion mutation.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Part BExperimental Treatment1 Intervention
Enrollment into the Phase 3 portion of the study will begin following completion of Part A.
Approximately 260 patients will be randomized on a 1:1 basis to receive pemetrexed and a platinum agent (either carboplatin or cisplatin) with or without zipalertinib on a 21-day cycle.
Carboplatin or cisplatin will be administered for 4 cycles. Patients may continue to receive zipalertinib (experimental study arm) and pemetrexed (both study arms) until documentation of PD or until other withdrawal criteria are met, whichever comes first.
Group II: Part A (Safety Lead in)Experimental Treatment1 Intervention
Part A: Safety Lead-In Approximately 6-12 patients will receive zipalertinib administered at an initial dose of zipalertinib PO BID (Dose Level 1) in combination with pemetrexed and carboplatin or cisplatin on a 21-day cycle. Patients may continue to receive study treatment until documentation of progressive disease (PD) or until other withdrawal criteria are met, whichever comes first.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Comprehensive Cancer Centers of Nevada - NorthwestLas Vegas, NV
Comprehensive Cancer Centers of Nevada - Central Valley - TwainLas Vegas, NV
Comprehensive Cancer Centers of Nevada - Horizon Ridge HendersonHenderson, NV
Comprehensive Cancer Centers of Nevada - SouthwestLas Vegas, NV
More Trial Locations
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Who Is Running the Clinical Trial?
Taiho Oncology, Inc.
Lead Sponsor
Trials
79
Patients Recruited
12,700+
References
Randomized phase II study of pemetrexed/cisplatin with or without axitinib for non-squamous non-small-cell lung cancer. [2021]The efficacy and safety of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 in combination with pemetrexed and cisplatin was evaluated in patients with advanced non-squamous non-small-cell lung cancer (NSCLC).
First-line osimertinib in patients with epidermal growth factor receptor-mutant non-small-cell lung cancer and with a coexisting low allelic fraction of Thr790Met. [2022]The AZENT (NCT02841579) study aimed to assess the efficacy and safety of first-line osimertinib in patients with epidermal growth factor receptor(EGFR)mutation-positive advanced non-small-cell lung cancer (NSCLC) and with a coexisting low allelic fraction of Thr790Met.
Phase 2 study of osimertinib in combination with platinum and pemetrexed in patients with previously untreated EGFR-mutated advanced non-squamous non-small cell lung cancer: The OPAL Study. [2023]This multicenter phase 2 trial evaluated the safety and efficacy of osimertinib and platinum-based chemotherapy (OPP) in patients with previously untreated EGFR-mutated advanced non-squamous non-small cell lung cancer (NSCLC).
Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours. [2021]This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours.
Osimertinib Versus Comparator EGFR TKI as First-Line Treatment for EGFR-Mutated Advanced NSCLC: FLAURA China, A Randomized Study. [2022]In the global FLAURA study, first-line osimertinib, a third-generation irreversible tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), significantly improved progression-free survival (PFS) and overall survival (OS) versus comparator EGFR TKIs in patients with EGFR mutation-positive (EGFRm) advanced non-small-cell lung cancer (NSCLC).
Lung Cancer Driven by BRAFG469V Mutation Is Targetable by EGFR Kinase Inhibitors. [2022]Mutations in BRAF occur in 2% to 4% of patients with lung adenocarcinoma. Combination dabrafenib and trametinib, or single-agent vemurafenib is approved only for patients with cancers driven by the V600E BRAF mutation. Targeted therapy is not currently available for patients harboring non-V600 BRAF mutations.
Mobocertinib in non-small cell lung cancer. [2022]Tyrosine kinase inhibitors (TKIs) have provided great benefit for patients with EGFR-mutant non-small cell lung cancer (NSCLC). While prior TKIs have demonstrated limited efficacy against exon 20 insertion mutations of EGFR (EGFR Ex20Ins), mobocertinib (TAK-788) is designed to specifically inhibit these Ex20Ins mutations. In a phase I/II clinical trial, mobocertinib demonstrated meaningful benefits among a cohort of platinum-pretreated patients with EGFR Ex20Ins mutant NSCLC. For this cohort, the objective response rate was 28% (95% confidence interval [CI], 20%-37%). The median progression-free survival and duration of response were 7.3 months (95% CI, 5.5-9.2) and 17.5 months (95% CI, 7.4-20.3), respectively, both by independent review committee assessment. On the basis of these results, mobocertinib was granted accelerated approval as the first TKI for treatment of this indication by the U.S. Food and Drug Administration (FDA) in 2021. This review summarizes the preclinical development of mobocertinib and the early-phase clinical data leading to its approval and discusses potential directions for mobocertinib's development.
Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. [2022]Label="BACKGROUND">BRAFV600E mutation occurs in 1-2% of lung adenocarcinomas and acts as an oncogenic driver. Dabrafenib, alone or combined with trametinib, has shown substantial antitumour activity in patients with previously treated BRAFV600E-mutant metastatic non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of dabrafenib plus trametinib treatment in previously untreated patients with BRAFV600E-mutant metastatic NSCLC.