InformationClinical trials have complex eligibility criteria.
Always talk to your clinician about you’re interest in participating in a trial.
Learn why

Optimise reading forHealth ProfessionalsPatients

Closed (no longer recruiting)Last updated: 27 November 2023

HERTHENA-Lung02: This study is comparing the effectiveness of immunotherapy (patritumab deruxtecan) with chemotherapy in people with metastatic or locally advanced non-small cell lung cancer with EGFR-activating mutationA Phase 3, Randomized, Open-label Study of Patritumab Deruxtecan Versus Platinum-based Chemotherapy in Metastatic or Locally Advanced Epidermal Growth Factor Receptor-mutated (EGFRm) Non-small Cell Lung Cancer (NSCLC) After Failure of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy (HERTHENA-Lung02)

Clinical summary


Eligible participants will be randomly allocated to either the Experimental or Active Comparator Arm. In the Experimental Arm, participants will receive patritumab deruxtecan (HER3-DXd), given intravenously, at a dose of 5.6mg/kg every 3 weeks. In the Active Comparator Arm, participants will receive platinum-based chemotherapy for 4 cycles: pemetrexed (500mg/m^2) plus either cisplatin (75mg/m^2) or carboplatin (target area under the curve 5 [AUC5] by using the Calvert formula). Chemotherapy will be administered intravenously every 3 weeks.


This trial is treating patients with non-small cell lung cancer with EGFR-activating mutation.


Lung Cancers Lung cancer





Trial Acronym


More information

Trial Identifiers

Use the hyperlinks, where available to access additional clinical trial information.

Trial sponsor

Daiichi Sankyo Ltd.

Scientific Title

A Phase 3, Randomized, Open-label Study of Patritumab Deruxtecan Versus Platinum-based Chemotherapy in Metastatic or Locally Advanced Epidermal Growth Factor Receptor-mutated (EGFRm) Non-small Cell Lung Cancer (NSCLC) After Failure of Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor (TKI) Therapy (HERTHENA-Lung02)



  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


  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


  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.
  • Your cancer has not spread to other parts of the body.
  • Your cancer has spread to other parts of the body.


  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
  • You have had certain treatments, surgical procedures or drugs.

Clinical trials have complex eligibility criteria.

Ask your doctor if this trial could be right for you.

Participating hospitals

+ Show non-recruiting hospitals

Closed hospitals

InformationTell us if you find this trial availability is not accurate.Report inaccuracy

Get Support


Cancer Connect

Speak with someone who has cancer clinical trial experience.

Learn more


Cancer Council’s cancer nurses

If you need cancer information and practical support for yourself, a carer, family or friend, contact Cancer Council’s experienced cancer nurses on 131120.

Learn more


Information for family, friends and carers

When you are considering a cancer clinical trial, it is a good idea to discuss it with your family, friends or carers.

Learn more

Victorian Cancer Registry Victorian Government

The Victorian Cancer Trials Link is supported by the Victorian Government through the Victorian Cancer Agency.


Cancer Council Victoria would like to acknowledge the traditional custodians of the land on which we live and work. We would also like to pay respect to the elders past and present and extend that respect to all other Aboriginal people.