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Lung Non-Squamous Non-Small Cell CarcinomaPhase 2NCT07229339

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

A Phase 2 study testing Biospecimen Collection, Carboplatin and Computed Tomography in people with Lung Non-Squamous Non-Small Cell Carcinoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Carboplatin and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
1 siteUnited States
Study dates
1 Jun 2027to 1 Jun 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Able to comply with study requirements
  • Female participants may not be pregnant or breastfeeding from initial study visit through a minimum of 1 month after last dose of zipalertinib or 6 months after last dose of chemotherapy, whichever is later
  • Adequate pulmonary function as defined by no requirement for oxygen supplementation

Who cannot join

  • 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
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  • 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
  • History of allogeneic organ transplant
  • History of hypersensitivity to carboplatin or pemetrexed or any excipients of zipalertinib
  • History of myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 3 months prior to first dose of study treatment
  • History of cerebral vascular accident (e.g., stroke or transient ischemic attack) within 3 months prior to first dose of study treatment
  • History of uncontrolled seizures
  • Human immunodeficiency virus (HIV) infection.
  • Participants with HIV infection on antiviral therapy and undetectable viral load are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on study per local or institutional guidelines
  • HIV screening is not required in the absence of clinical suspicion
  • Active hepatitis C infection.
  • Defined as participants with detectable hepatitis C antibody [HCV Ab] and hepatitis C virus [HCV] ribonucleic acid (RNA) viral load above the limit of quantification
  • Participants with presence of HCV antibody (HCV Ab positive) and HCV RNA viral load below the limit of quantification (HCV RNA negative) with or without prior treatment are allowed
  • Active hepatitis B infection.
  • Defined as presence of hepatitis B surface antigen [HBsAg-positive] and hepatitis B virus [HBV] DNA viral load above the limit of quantification [HBV DNA positive]
  • Participants with resolved HBV infection defined as absence of HBV surface antigen (HBsAg-negative) and presence of HBV core antibody (anti-HBc positive) followed by an HBV DNA viral load below the limit of quantification (HBV DNA negative) are allowed, with a requirement for regular monitoring for reactivation for the duration of treatment on the study and assessing the need for HBV prophylaxis therapy per local or institutional guidelines.
  • Participants with chronic HBV infection inactive carriers state, defined as presence of HBV surface antigen (HBsAg-positive) and HBV DNA viral load below the limit of quantification (HBV DNA negative) are allowed, with a requirement for regular monitoring for reactivation for the duration of treatment on the study and assessing the need for HBV prophylaxis therapy per local or institutional guidelines
  • Any condition (concurrent disease, infection, or comorbidity), in the opinion of the Investigator, that interferes with ability to participate in the study, causes undue risk, or complicates the interpretation of safety data

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Lia R. Ethridge contact

4243871086

letheridge@mednet.ucla.edu

Tina Tieu contact

310-633-8400

TinaTieu@mednet.ucla.edu

United States1 site

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California, 90095

    Tina Tieu, 310-633-8400, tinatieu@mednet.ucla.edu

    Lia R. Ethridge, 4243871086, letheridge@mednet.ucla.edu

Other trials in United States

About this study

Official title: Phase 2 Trial of Zipalertinib in Patients With Resectable Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion or Uncommon/Compound Mutations

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To evaluate the major pathologic response (MPR) rate of neoadjuvant zipalertinib plus carboplatin and pemetrexed chemotherapy at time of surgery in patients with resectable EGFR Ex20ins-mutated or uncommon/compound EGFR-mutated non-squamous non small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

  1. To evaluate the efficacy of zipalertinib plus chemotherapy as measured by overall response rate (ORR), pathologic complete response (pCR), event-free survival (EFS), and nodal downstaging.

II. To evaluate the safety and tolerability of zipalertinib plus chemotherapy.

EXPLORATORY OBJECTIVE:

  1. To assess potential prognostic and predictive biomarkers using circulating tumor deoxyribonucleic acid (DNA) dynamics through next-generation sequencing using the Tempus platform.

OUTLINE:

NEOADJUVANT: Patients receive zipalertinib orally (PO) twice daily (BID) on days 1-21, and carboplatin intravenously (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 positron emission tomography (PET)/computed tomography (CT) scan and/or magnetic resonance imaging (MRI) during screening and CT scan and blood and urine sample collection throughout the study.

After completion of study treatment, patients are followed up at 30 days and every 12 weeks for up to 1 year or until cancer progression or initiation of a new cancer therapy, whichever occurs first.

Being tested
Biospecimen Collection, Carboplatin, Computed Tomography, Magnetic Resonance Imaging, Pemetrexed

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood and urine sample collection

  • CarboplatinDrug

    Also called Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • PemetrexedDrug

    Also called MTA, Multitargeted Antifolate, Pemfexy

    Given IV

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET scan

  • ZipalertinibDrug

    Also called CLN 081, CLN-081, CLN081, EGFR Mutant-specific Inhibitor CLN-081

    Given PO

Study groups in NCT07229339
Study groupRoleWhat they receive
Treatment (Zipalertinib, carboplatin, pemetrexed)ExperimentalNEOADJUVANT: 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.
Receives: Procedure: Biospecimen Collection; Drug: Carboplatin; Procedure: Computed Tomography; Procedure: Magnetic Resonance Imaging; Drug: Pemetrexed; Procedure: Positron Emission Tomography; Drug: Zipalertinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At time of surgery

Secondary outcomes (5)

  1. Overall response rate (ORR)

    Defined as complete response or partial response by Response Evaluation Criteria in Solid Tumors 1.1 criteria. ORR estimate and its associated 95% confidence interval will be calculated. Will compute the proportion of participants achieving complete response (CR) or partial response (PR) and compute 95% confidence intervals using the exact (Clopper-Pearson) confidence intervals.

    Measured: Up to 2 years

  2. Pathologic complete response

    Defined as no viable tumor present histologically in the resected tumor specimen. Will compute the proportion of participants achieving CR or PR and compute 95% confidence intervals using the exact (Clopper-Pearson) confidence intervals.

    Measured: Up to 2 years

  3. Event free survival (EFS)

    Will be analyzed using the Kaplan-Meier method. Median EFS and corresponding 95% confidence intervals will be reported.

    Measured: 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

  4. Nodal downstaging

    Defined as having N2 or N1 disease prior to the initiation of neoadjuvant treatment with subsequent nodal downstaging to N1 or N0 disease at time or surgery. Will be reported as a percentage of participants who achieve histological downstaging at time of surgery.

    Measured: From baseline to surgery

  5. Incidence of adverse events

    Will be assessed using Common Terminology Criteria for Adverse Events version 5.0.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Nov 2025
  2. Study start1 Jun 2027 (estimated)
  3. Primary completion1 Jun 2029 (estimated)
  4. Study completion1 Jun 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07229339
Sponsor's protocol ID
25-1863
Other IDs
NCI-2025-08031
Status last verified
Feb 2026
First submitted
12 Nov 2025
Last updated
5 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Carboplatin and Computed Tomography in people with Lung Non-Squamous Non-Small Cell Carcinoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 5 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Lia R. Ethridge (4243871086, letheridge@mednet.ucla.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major pathologic response (time frame: At time of surgery). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07229339.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2026.

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