HERTHENA-Lung02: A Study of Patritumab Deruxtecan Versus Platinum-based Chemotherapy in Metastatic or Locally Advanced EGFRm NSCLC After Failure of EGFR TKI Therapy

Study summary

Disease progression is typical for patients with epidermal growth factor receptor mutated (EGFRm) non-small cell lung cancer (NSCLC). Standard platinum-based chemotherapy offers limited efficacy and an unfavorable safety profile. There is an urgent need for more effective and tolerable therapies for patients with EGFRm NSCLC who have exhausted available targeted therapies. Clinical evidence suggests that patritumab deruxtecan constitutes a promising investigational therapy for patients with EGFRm NSCLC.

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Key things to know

Main goalTreatment

This describes the study’s primary purpose.

What is being studiedPatritumab Deruxtecan and Platinum-based chemotherapy

The study team can explain what participation involves.

Who it may be forNon-small cell lung cancer (NSCLC) · EGFR · Locally advanced

These are broad labels—not an eligibility decision.

Checked against the public recordLast updated Aug 27, 2026 · Source: ClinicalTrials.gov

Is enrollment open?Active Not Recruiting

The study is underway but is not accepting new participants.

What kind of study?Phase 3

Interventional

Where is it offered?182 U.S. locations

Locations may change over time.

Who runs it?Daiichi Sankyo

Study sponsor

Study overview

What this study is about

Purpose: Treatment
Study type: Interventional
Phase: Phase 3
Sponsor: Daiichi Sankyo
Interventions being studied: Drug: Patritumab Deruxtecan; Drug: Platinum-based chemotherapy

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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

Locally advanced→Metastatic or stage IV→

Biomarkers

EGFR→

Treatment approach

Targeted therapy→Chemotherapy→

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. Is a male or female subject aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is \>18 years old). 2. Has histologically or cytologically documented metastatic or locally advanced non-squamous NSCLC not amenable to curative surgery or radiation. 3. Has documentation of an EGFR-activating mutation detected from tumor tissue or blood sample: exon 19 deletion or L858R at diagnosis or thereafter. 4. Received 1 or 2 prior line(s) of an approved EGFR TKI treatment in the metastatic or locally advanced setting, which must include a third -generation EGFR TKI. 5. May have received either neoadjuvant and/or adjuvant treatment if progression to metastatic or locally advanced disease occurred at least 12 months after the last dose of such therapy and subsequently experienced disease progression on or after third-generation EGFR TKI treatment administered in the metastatic or locally advanced setting. 6. Has not received any other prior systemic therapies in the metastatic or locally advanced setting (including chemotherapy, immunotherapy etc) (even if administered in combination with EGFR TKI). 7. Has documentation of radiographic disease progression while receiving or after receiving a third generation EGFR TKI for metastatic or locally advanced disease. 8. Has at least 1 measurable lesion as per RECIST v1.1 by Investigator assessment. 9. Is willing to have a tumor biopsy or provide recently obtained tumor tissue. 10. Has an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening. 11. Has adequate bone marrow reserve and organ function based on local laboratory evaluation within 14 days prior to randomization:
Platelet count: ≥100,000/mm\^3 or ≥100 × 10\^9/L within 14 days prior to the assessment of platelet count during the Screening Period
Absolute neutrophil count: ≥1500/mm\^3 or ≥1.5 × 10\^9/L within 14 days prior to the assessment of absolute neutrophil count during the Screening Period
Hemoglobin (Hgb): ≥9.0 g/dL within 14 days prior to the assessment of hemoglobin during the Screening Period
Creatine clearance (CrCl): CrCl ≥45 mL/min calculated by using the Cockcroft-Gault equation or measured CrCl
Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT): AST/ALT ≤3× Upper limit of normal (ULN)
Total bilirubin (TBL): TBL ≤1.5 × ULN
Serum albumin: ≥2.5 g/dL
Prothrombin time (PT) or Prothrombin time-International normalized ratio (PT-INR) and activated partial thromboplastin time (aPTT)/partial thromboplastin time (PTT): ≤1.5 × ULN, except for participants receiving coumarin-derivative anticoagulants or other similar anticoagulant therapy who must have PT-INR within therapeutic range as deemed appropriate by the Investigator

Reasons someone may not be able to joinExclusion criteria

1. Has any previous histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy, or squamous NSCLC histology. 2. Has any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during Screening. 3. Has clinically severe respiratory compromise (based on the Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to the following:
Any underlying pulmonary disorder, restrictive lung disease, or pleural effusion
Any autoimmune, connective tissue, or inflammatory disorders where there is documented, or a suspicion of pulmonary involvement at the time of Screening
OR prior complete pneumonectomy 4. Is receiving chronic systemic corticosteroids dosed at \>10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to randomization. 5. Has any history of or evidence of current leptomeningeal disease. 6. Has evidence of clinically active spinal cord compression or brain metastases, defined as being symptomatic and untreated, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. 7. Any prior treatment with any agent including an antibody drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase I, human epidermal growth factor receptor 3 (HER3) antibody, and any systemic therapies (other than EGFR TKIs) in the metastatic/locally advanced setting, including chemotherapy or any other systemic therapy in combination with an EGFR TKI. 8. Has history of other active malignancy within 3 years prior to randomization, except for adequately resected nonmelanoma skin cancer, adequately treated intraepithelial carcinoma of the cervix, and any other curatively treated in situ disease. 9. Has uncontrolled or significant cardiovascular disease prior to randomization. 10. Has active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of active viral infection within 28 days of randomization. 11. Has a known human immunodeficiency virus (HIV) infection that is not well controlled. 12. Has clinically significant corneal disease.

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

Alaska Oncology and Hematology LLCAnchorage, Alaska
Highlands OncologySpringdale, Arkansas
City of HopeDuarte, California
Moores Cancer Center at the UC San Diego HealthLa Jolla, California
Scripps MD Anderson Cancer CenterLa Jolla, California
USC Norris Comprehensive Cancer CenterLos Angeles, California
Kaiser Permanente - Vallejo Medical CenterVallejo, California
Innovative Clinical Research InstituteWhittier, California
Sarah Cannon/Florida Cancer Specialists - FCS SouthPort Charlotte, Florida
Emory UniversityAtlanta, Georgia
St Luke's Cancer InstituteBoise, Idaho
American Oncology Partners of MarylandBethesda, Maryland

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Aug 27, 2026. Always confirm current availability with the study team.

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