EGFRPhase 2NCT07802834
Adjuvant ctDNA-Adapted Treatment With Zipalertinib in Early-Stage Atypical EGFR-Mutant NSCLC
A Phase 2 study testing Zipalertinib in people with EGFR and Lung Cancer (NSCLC), run by Stanford University.
Trial summary
This study will evaluate the novel, oral EGFR TKI, zipalertinib, in the adjuvant ctDNA-adapted treatment of stage IA2 to IIIC atypical EGFR-mutant NSCLC after completion of definitive therapy with a primary endpoint of molecular response in participants identified as having minimal residual disease (MRD). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- EGFR, Lung Cancer (NSCLC), Non Small Cell Lung Cancer
- What is being tested?
- Zipalertinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- No sites listed yet
- Study dates
- Nov 2026to Dec 2028
- Phase
- Phase 2
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
- Histological documentation of NSCLC (squamous histology is permitted).
- Clinical or pathological stage IA2 to IIIC or locoregionally recurrent disease based on AJCC 9th edition.
- Stage IA1 tumors are excluded unless radiographic solid component or pathologic invasive component of > 10 mm.
- Documented atypical EGFR mutation (defined as non-exon 19 deletion or L858R) including but not limited to exon 20 insertion, E709X, G719X, S768I, L861X, exon 19 insertion, and others (which may be allowed with study PI/Co-PI permission) as demonstrated by a test routinely used by each institution and performed in a CLIA-certified or equivalent laboratory.
- Tumors harboring more than one atypical EGFR mutation are permitted; but patients with tumors harboring compound EGFR mutations including a classical mutation (exon 19 deletion or L858R mutation) are excluded.
- Completed all planned curative-intent therapy with surgery and/or radiation. May have received neoadjuvant/adjuvant chemotherapy; but patients that received prior concurrent chemotherapy and radiation are excluded.
Show all 23Show fewer
- For patients with non-squamous NSCLC in whom neoadjuvant and/or adjuvant chemotherapy is standard-of-care (i.e., patients with stage IIA-IIIA disease), these patients must have received chemotherapy in the neoadjuvant and/or adjuvant setting, unless they refused or were considered unsuitable for chemotherapy.
- No known current radiographic or pathologic residual/recurrent disease after completion of all intended therapy (for example, positive margins after surgery without adjuvant radiotherapy, or unequivocal radiographic evidence of residual or recurrent disease).
- A known positive or negative result from a commercial tumor-informed MRD test that was collected as standard-of care between 2 weeks and 24 weeks of completion of curative-intent therapy (including adjuvant chemotherapy) and has resulted, with intention for serial testing to continue for at least 3 years.
- Note: Recommended assay is second-generation "Signatera Genome". Other tumor-informed commercial assays and/or a longer window since completion therapy of may be considered but require study PI/Co-PI approval for enrollment.
- Age ≥ 18 years old
- Has not received immune checkpoint inhibitor (ICI) therapy (PD-1, PD-L1, or CTLA-4 antibodies) within 12 weeks prior to enrollment, and not planned to receive ICI therapy.
- Has not received another systemic anti-cancer investigational product during the 4 weeks prior to enrollment.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Have the following laboratory values:
- Serum creatinine < 1.5 × ULN or if higher than normal range, calculated creatinine clearance (CrCl) must be ≥ 50 mL/min/1.73 m2 (by Cockroft-Gault formula); actual body weight must be used for CrCl unless BMI >30 kg/m2 then lean body weight must be used
- Total bilirubin ≤ 1.5 × ULN unless prior history of Gilbert's syndrome
- Aspartate transaminase and alanine transaminase ≤ 2.5 × ULN
- Hemoglobin ≥ 9.0 g/dL in the absence of transfusion ≤ 14 days prior to study enrollment
- Platelets ≥ 100 × 109 cells/L and no platelet transfusion within 14 days
- Absolute neutrophil count ≥ 1.5 ×109 cells/L
- Ability to understand and the willingness to sign a written informed consent document.
- Female participants must use adequate contraceptive measures, must not be breast feeding, and must have a negative pregnancy test prior to first dose of study drug and during the study and 30 days after last dose of zipalertinib; or female patients must have evidence of non-childbearing potential. Male participants must use adequate contraceptive measures during the study and 30 days after last dose of zipalertinib.
Who cannot join
- Any component of small cell lung cancer, for example mixed small cell and non-small cell lung cancer histology.
- Tumor harbors a classical EGFR mutation (exon 19 deletion or L858R), even in combination with atypical mutations.
- Prior treatment with any EGFR targeting drug, including zipalertinib.
- Prior treatment with any adjuvant immune checkpoint inhibitor. Neoadjuvant immune checkpoint inhibitor may be allowed with study PI/Co-PI review and permission.
- Have any unresolved toxicity of Grade ≥ 2 from previous anti-cancer treatment, except for alopecia and skin pigmentation. Patients with chronic but stable Grade 2 toxicities may be allowed to enroll after agreement from the PI/Co-PI.
- Past medical history of drug-induced interstitial lung disease or treatment-related pneumonitis which required steroid treatment.
Show all 18Show fewer
- OR History of or clinically active interstitial lung disease.
- Cardiac conditions as follows: Patient has a history of congestive heart failure (CHF) Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment.
- Persistent resting corrected QT interval by Fridericia (QTcF) > 470 msec during screening.
- Unable to take study therapy orally, for example due to disorders or diseases that may affect gastrointestinal function, including but not limited to inflammatory bowel diseases (e.g., Crohn's disease, ulcerative colitis) or malabsorption syndrome, or procedures that may affect gastrointestinal function, such as gastrectomy, enterectomy, or colectomy.
- Have any condition or illness that, in the opinion of the investigator, might compromise the efficacy or safety of the drug, such as active bleeding disorders, uncompensated respiratory, cardiac, hepatic, or renal disease, conditions causing GI malabsorption, or issues swallowing pills.
- History of another primary malignancy and currently undergoing active treatment.
- Exception: May participate if receiving adjuvant endocrine therapy for breast or prostate cancer with approval from PI/Co-PI.
- Clinically significant ongoing or active infection (for example, requiring IV antibiotics).
- For patients with a history of hepatitis B, active infection as defined by a positive HBsAg test and detectable HBV DNA.
- Note: Patients ineligible due to detectable levels of HBV DNA at baseline may be rescreened for enrollment if their HBV DNA levels become undetectable after treatment with antiviral agents.
- For patients with a history of hepatitis C, active infection as defined by a reactive HCV antibody test and detectable HCV RNA.
- In the Investigator's opinion, unable or unwilling to comply with the trial procedure, for example due to psychiatric illness/social situations.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Adjuvant ctDNA-Adapted Personalized Treatment With Zipalertinib in Early-Stage Atypical EGFR-Mutant NSCLC
This study will evaluate the novel, oral EGFR TKI, zipalertinib, in the adjuvant ctDNA-adapted treatment of stage IA2 to IIIC atypical EGFR-mutant NSCLC after completion of definitive therapy with a primary endpoint of molecular response in participants identified as having minimal residual disease (MRD).
- Conditions
- EGFR, Lung Cancer (NSCLC), Non Small Cell Lung Cancer
- Being tested
- Zipalertinib
- Keywords
- Zipalertinib, lung cancer, non small cell lung cancer
- Medical subject headings
- Lung Neoplasms, Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZipalertinibDrug
Zipalertinib will be administered to participants allocated to the Treatment MRD+ Arm of this study on the basis of MRD positivity at study entry or on repeat assessment.
Zipalertinib will begin on Cycle 1 Day 1 and will be self-administered at 100 mg oral (PO) twice daily (BID) every day in each 21-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Arm (MRD+) | Experimental | Participants will receive adjuvant treatment with zipalertinib up to 3 years Receives: Drug: Zipalertinib |
| Surveillance Arm (MRD-) | No intervention | Participants will receive active surveillance up to 3 years |
What is being measured
The primary outcome is the main question the study is designed to answer.
Molecular response rate at 12 weeks
To measure the molecular response rate at 12 weeks of adjuvant zipalertinib in the Treatment MRD+ Arm.
Measured: 12 weeks
Secondary outcomes (3)
Disease-free survival (DFS)
To evaluate the 3-year disease-free survival (DFS) rate among all participants.
Measured: 3 years
Overall survival (OS) rate
To evaluate the 3-year overall survival (OS) rate among all participants.
Measured: 3 years
Incidence and Severity of Adverse Events
Number of participants experiencing adverse events and severity of adverse events, graded according to NCI CTCAE v5.0, during treatment with zipalertinib in the MRD+ Treatment Arm.
Measured: From first dose of zipalertinib through 30 days after the last dose, up to approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2026
- Study startNov 2026 (estimated)
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EGFRStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Taiho Oncology, Inc., National Comprehensive Cancer Network
- Responsible party
- Sponsor
- Investigators
- Joel Neal, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07802834
- Sponsor's protocol ID
- IRB-86170
- Status last verified
- Aug 2026
- First submitted
- 27 Aug 2026
- Last updated
- 3 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No