A Phase 1a/1b Of Zanidatamab In Combination With Zongertinib In HER2-Mutated Non-Small Cell Lung Cancer (NSCLC)

Study summary

This is a Phase Ia/Ib, open-label study evaluating the concurrent administration of zanidatamab and zongertinib in patients with advanced, unresectable, or metastatic non-small lung cancer harboring HER2 alterations.

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Key things to know

Main goalTreatment

This describes the study’s primary purpose.

What is being studiedZanidatamab and Zongertinib

The study team can explain what participation involves.

Who it may be forNon-small cell lung cancer (NSCLC) · HER2 · Early-stage or resectable

These are broad labels—not an eligibility decision.

Checked against the public recordLast updated Oct 28, 2026 · Source: ClinicalTrials.gov

Is enrollment open?Not Yet Recruiting

The study is not accepting participants yet.

What kind of study?Phase 1

Interventional

Where is it offered?1 U.S. location

Locations may change over time.

Who runs it?M.D. Anderson Cancer Center

Study sponsor

Study overview

What this study is about

Purpose: Treatment
Study type: Interventional
Phase: Phase 1
Sponsor: M.D. Anderson Cancer Center
Interventions being studied: Drug: Zanidatamab; Drug: Zongertinib

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How this study is categorized

These labels come from structured fields and exact terms in the public record.

Cancer type

Non-small cell lung cancer (NSCLC)→

Disease setting

Early-stage or resectable→Metastatic or stage IV→

Biomarkers

HER2→

Treatment approach

Targeted therapy→

Public criteria

Who may be able to participate

The sponsor separates these requirements into two groups. You do not need to interpret them alone—use them to guide a conversation with the study team.

Requirements people may need to meetInclusion criteria

1. Age ≥ 18 years at the time of consent. 2. Histologically or cytologically confirmed diagnosis of an advanced, unresectable and/or metastatic non-small cell lung cancer (NSCLC). 3. Baseline archival tumor tissue available, either from primary or metastatic sites. If archival material is not available, a fresh tumor biopsy should be performed if feasible and if the procedure poses no significant risk for the participant. 4. Next generation sequencing (NGS) test documenting activating HER2 mutation in the tyrosine kinase domain assessed by a Clinical Laboratory Improvement Amendments (CLIA)-certified (United States \[US\] sites) or an equally accredited (outside of the US) local laboratory. 5. Patients may be treatment-naïve in the advanced/metastatic setting (limited to a maximum of 12 patients) or may have received prior systemic therapy for advanced/metastatic disease. Prior treatment with HER2-targeted agents (including sevabertinib, zongertinib, and trastuzumab deruxtecan), cytotoxic chemotherapy, and immunotherapy is allowed. 6. Must have at least one measurable cancer lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) 7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. 8. Ability to take pills or capsules by mouth. 9. Life expectancy of at least 12 weeks at the start of treatment in the opinion of the investigator. 10. Patients must have adequate bone marrow and organ functions as defined:
Hemoglobin ≥9 g/dL
ANC ≥1.0 x 109 /L
Platelets ≥75 x 10 ⁹ /L
AST and ALT ≤3 x ULN if no demonstrable liver metastases, or otherwise ≤ 5 x ULN if transaminase elevation is attributable to liver metastases.
Total bilirubin ≤1.5 x ULN; subjects with Gilbert's syndrome can enroll if conjugated bilirubin is within normal limits
Serum creatinine \<1.5 x ULN or calculated or estimated glomerular filtration rate \>50 mL/min/1.73 m2 calculated using the Chronic Kidney Disease Epidemiology (CKD-EPI) formula 11. Recovered from any previous therapy-related toxicity to CTCAE Grade 1 or lower at start of treatment (except for alopecia, stable sensory neuropathy and hypothyroidism). 12. The effects of zanidatamab in combination with zongertinib on the developing human fetus are unknown. For this reason and because these agents as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to treatment initiation and for the duration of study treatment and for at least 4 months after the last dose of study intervention. (Refer to Pregnancy Assessment Policy UT MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
Postmenopausal (no menses in greater than or equal to 12 consecutive months).
History of hysterectomy or bilateral salpingo-oophorectomy.
Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
History of bilateral tubal ligation or another surgical sterilization procedure
Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
Men treated or enrolled on this protocol must also agree to use adequate contraception for the duration of study treatment and for at least 4 months after the last dose of study intervention. 13. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. 14. Ability to understand and the willingness to sign a written informed consent document. 15. CNS metastasis are allowed as long as asymptomatic and stable - defined as patients who are either off steroids or on a low dose (prednisone \<10 mg/day), with no neurological symptoms and no evidence of radiographic progression for at least 2 weeks prior to the study screening.

Reasons someone may not be able to joinExclusion criteria

1. Prior or concurrent malignancy whose natural history or treatment has, in the opinion of the investigator or medical monitor, the potential to interfere with the safety or efficacy assessment of the investigational regimen. 2. Patients who have not recovered from adverse events due to prior anti-cancer therapy (have residual toxicities \> Grade 1) except for alopecia, stable neuropathy, hypothyroidism and parameters superseded by other eligibility criteria \[e.g., laboratory parameters\]). 3. Any of the following cardiac criteria:
Baseline left ventricular ejection fraction (LVEF) \< 50% or history of symptomatic congestive heart failure (New York Heart Association Class II to IV).
Any Grade 2 or higher CHF related to a prior anti-cancer therapy. If grade 1 CHF occurred with prior treatment, it needs to be completely resolved prior to enrollment
Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval \>250msec
Prolonged QTc interval (\>470 milliseconds for women and \>450 milliseconds for men), or medical history of congenital Long QT Syndrome.
The patient has experienced any arterial thromboembolic events, including but not limited to myocardial infarction, transient ischemic attack, cerebrovascular accident, or unstable angina, within 6 months prior to first dose of protocol therapy. 4. Any evidence of severe or uncontrolled systemic diseases. Screening for chronic conditions is not required. 5. Presence or history of uncontrolled or symptomatic brain metastases, unless considered stable by the investigator - defined as patients who are either off steroids or on a low dose (prednisone \<10 mg/day), with no neurological symptoms. 6. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of zongertinib. 7. Pregnant women are excluded from this study because zanidatamab in combination with zongertinib is HER2-inhibiting antineoplastic class of agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with zanidatamab and zongertinib, breastfeeding should be discontinued if the mother is treated with either agent. These potential risks may also apply to other agents used in this study.. 8. Patients not expected to comply with the protocol requirements or not expected to complete the trial as scheduled (e.g. chronic alcohol or drug abuse or any other condition that, in the investigator's opinion, makes the patient an unreliable trial participant) 9. History of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in drug formulation. 10. Active or history of \>Grade 2 interstitial lung disease/pneumonitis. 11. Patients who are receiving any other investigational agents 12. Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. 13. Patients with psychiatric illness/social situations that would limit compliance with study requirements.

Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.

Study sites

U.S. locations

UT MD AndersonHouston, Texas

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Oct 28, 2026. Always confirm current availability with the study team.

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