Zipalertinib With Carboplatin and Pemetrexed for the Treatment of Resectable, Stage II-IIIB, Non-Small Cell Lung Cancer

NCT07229339 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 25-1863NCI-2025-08031
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well zipalertinib with carboplatin and pemetrexed works in treating stage II-IIIB non small cell lung cancer. that can be removed by surgery (resectable). Zipalertinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of tumor cells. Pemetrexed is in a class of medications called antifolate antineoplastic agents. It works by stopping cells from using folic acid to make DNA and may kill tumor cells. Giving zipalertinib with carboplatin and pemetrexed may kill more tumor cells in patients with resectable, stage II-IIIB non-small cell lung cancer.

Conditions

Lung Non-Squamous Non-Small Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Major pathologic response

  Defined as ≤10% viable tumor present histologically in the resected tumor specimen after neoadjuvant treatment. A 95% confidence interval for the MPR rate will be calculated using the Clopper-Pearson (exact binomial) method.

  At time of surgery

Secondary Outcomes (5)

• Overall response rate (ORR)

  Up to 2 years

• Pathologic complete response

  Up to 2 years

• Event free survival (EFS)

  From cycle 1 day 1 to the earliest date of radiographic progression or recurrence, decision to forgo surgery, or death due to any cause, up to 2 years. Each cycle is 21 days

• Nodal downstaging

  From baseline to surgery

• Incidence of adverse events

  Up to 2 years

Study Arms (1)

Treatment (Zipalertinib, carboplatin, pemetrexed)

EXPERIMENTAL

NEOADJUVANT: Patients receive zipalertinib PO BID on days 1-21, and carboplatin IV, over 15-60 minutes, and pemetrexed IV, over 10 minutes, on day 1 of each cycle. Cycles repeat every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Within 30 days patients undergo standard of care resection surgery. ADJUVANT: Between 4 and 12 weeks after surgery patients receive zipalertinib PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for 13 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT scan and/or MRI during screening and CT scan and blood and urine sample collection throughout the study.

Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Pemetrexed; Procedure: Positron Emission Tomography; Drug: Zipalertinib

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (Zipalertinib, carboplatin, pemetrexed)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (Zipalertinib, carboplatin, pemetrexed)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (Zipalertinib, carboplatin, pemetrexed)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (Zipalertinib, carboplatin, pemetrexed)

Pemetrexed DRUG

Given IV

Also known as: MTA, Multitargeted Antifolate, Pemfexy

Treatment (Zipalertinib, carboplatin, pemetrexed)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (Zipalertinib, carboplatin, pemetrexed)

Zipalertinib DRUG

Given PO

Also known as: CLN 081, CLN-081, CLN081, EGFR Mutant-specific Inhibitor CLN-081, Mutation-specific EGFR TKI TAS6417, Pan- EGFR Inhibitor CLN-081, Pan-mutation-selective EGFR Inhibitor CLN-081, Pan-mutation-selective EGFR Tyrosine Kinase Inhibitor CLN-081, TAS 6417, TAS-6417, TAS6417

Treatment (Zipalertinib, carboplatin, pemetrexed)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has provided informed consent prior to initiation of any study specific activities/procedures
• Male or female ≥ 18 years of age at time of enrollment and willing and able to provide informed consent
• Histologically confirmed non-squamous NSCLC performed within 90 days of enrollment with EGFR Ex20Ins-mutated (addition of 1 or more amino acids) or uncommon/compound EGFR mutations (E709X, G719X, L747X, S758I, and/or L861Q) in tumor tissue or blood; any one of these mutations would qualify if compounded with another EGFR mutation
• Staging positron emission tomography-computed tomography (PET-CT) and brain magnetic resonance imaging (MRI) within 60 days of enrollment demonstrating stage II, IIIA, or IIIB (N2) NSCLC (American Joint Commission for Cancer \[AJCC\] version \[v\] 9); mediastinal staging is required by bronchoscopy or mediastinoscopy
• No prior systemic treatment for lung cancer
• Resectable and operable as determined by thoracic surgeon
• At least one measurable lesion according to Response Evaluation Criteira in Solid Tumors (RECIST) 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Absolute neutrophil count (ANC) ≥ 1.0 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Hemoglobin ≥ 9 g/dL without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment)
• Glomerular filtration rate (GFR; by Cockroft-Gault or equivalent estimation) ≥ 45 mL/min/1.73 m\^2
• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \> 1.5 ULN with the exception of participants with Gilbert's disease
• Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x ULN
• International normalized ratio (INR) or prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants

You may not qualify if:

• Concurrent enrollment in another therapeutic clinical study, unless enrolled only in the follow-up period or an observational study. Use of any antineoplastic therapy must not have been received within 30 days prior to the treatment initiation
• Treatment with live virus, including live-attenuated vaccination, within 30 days prior to the first dose of study treatment. Treatment with inactive vaccines (e.g., non-live or non-replicating agent) and live viral non-replicating vaccines within 3 days prior to first dose of study treatment
• History of active primary immunodeficiency
• Mixed small cell and NSCLC histology
• Stages I, IIIB (N3), IIIC, IVA, and IVB NSCLC, including leptomeningeal carcinomatosis or other central nervous system (CNS) metastases
• History of noninfectious pneumonitis that required the use of systemic corticosteroids, history of interstitial lung disease, treatment-related pneumonitis (any grade), or any evidence of clinically active interstitial lung disease
• Unable to swallow tablets or has any disease or condition that may significantly effect gastrointestinal (GI) absorption of zipalertinib (such as active inflammatory bowel disease, malabsorption syndrome, or prior GI resection)
• History of other malignancy within the past 2 years, with the following exceptions:
• Malignancy treated with curative intent before enrollment, with no known active disease and felt to be at low risk for recurrence by the treating physician, after discussion with the medical monitor.
• Adequately treated non-melanomatous skin cancer or lentigo maligna without evidence of disease.
• Adequately treated cervical carcinoma in situ without evidence of disease.
• Adequately treated breast ductal carcinoma in situ disease or early stage breast cancer without evidence of disease.
• Prostatic intraepithelial neoplasia without evidence of prostate cancer, or localized prostate cancer that is adequately treated.
• Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ
• Diagnosis of myelodysplastic syndrome (MDS) requiring active MDS-directed treatment

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Taiho Oncology, Inc.: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Interventions

Specimen Handling; Carboplatin; Magnetic Resonance Spectroscopy; Pemetrexed; zipalertinib

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Coordination Complexes; Organic Chemicals; Spectrum Analysis; Chemistry Techniques, Analytical; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Arjan Gower, MD

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lia R. Ethridge

CONTACT

4243871086; letheridge@mednet.ucla.edu

Tina Tieu

CONTACT

310-633-8400; TinaTieu@mednet.ucla.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 12, 2025
• First Posted: November 17, 2025
• Study Start (Estimated): June 1, 2027
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: February 5, 2026

Record last verified: 2026-02

Locations

US (1)