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NCT04619004

HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer

Active, enrolled Phase 2 Results posted Last updated 7 April 2026
What this trial tests

Phase 2 trial testing Patritumab Deruxtecan (Fixed dose) in Non-Small Cell Lung Cancer Metastatic in 277 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline
2 February 2021
Primary endpoint
21 November 2022
3 July 2026

Quick facts

Lead sponsorDaiichi Sankyo
PhasePhase 2
StatusActive, enrolled
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment277
Start date2 February 2021
Primary completion21 November 2022
Estimated completion3 July 2026
Sites123 locations across France, Italy, Japan, Netherlands, Belgium, Austria, Taiwan, United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

Daiichi Sankyo — full company profile →

Who can join

18 and older, any sex, with Non-Small Cell Lung Cancer Metastatic or Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) Primary · Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months

ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions based on RECIST v1.1.

GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg64
Patritumab Deruxtecan Up-Titration8
Duration of Response (DoR) Secondary · Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months

DoR is defined as the time from the first documented confirmed response (CR or PR) to the date of progression or death due to any cause as assessed by BICR and Investigator per RECIST v1.1, respectively. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

Duration of response (BICR)
GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg6.04.4 – 7.2
Patritumab Deruxtecan Up-Titration7.12.8 – 15.2
Duration of response (Investigator)
GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg6.95.6 – 7.2
Patritumab Deruxtecan Up-Titration5.12.6 – 9.5
Progression-free Survival (PFS) Secondary · Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months

PFS is defined as the time from the start of study treatment to the first documentation of objective progressive disease (PD) per RECIST v1.1 or death due to any cause. PFS will be determined by BICR and by Investigator, respectively.

Progression-free survival (BICR)
GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg5.55.1 – 5.9
Patritumab Deruxtecan Up-Titration6.74.2 – 8.8
Progression-free survival (Investigator)
GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg5.54.2 – 5.7
Patritumab Deruxtecan Up-Titration5.34.0 – 8.2
Objective Response Rate (ORR) as Assessed by the Investigator Secondary · Data collected from screening until time of disease progression, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months

ORR is defined as the proportion of participants with a BOR of confirmed CR or confirmed PR as assessed by the Investigator per RECIST v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg56
Patritumab Deruxtecan Up-Titration8
Disease Control Rate (DCR) Secondary · Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months

DCR is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD) as assessed by BICR and by the Investigator per RECIST v1.1, respectively. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.

Disease control rate (BICR)
GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg166
Patritumab Deruxtecan Up-Titration38
Disease control rate (Investigator)
GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg169
Patritumab Deruxtecan Up-Titration37
Time to Tumor Response (TTR) Secondary · Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months

TTR is defined as the time from the start of study treatment to the date of the first documentation of confirmed response (CR or PR) as assessed by BICR and Investigator per RECIST v1.1, respectively. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions.

Time to response (BICR)
GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg2.2± 1.31
Patritumab Deruxtecan Up-Titration1.7± 0.61
Time to response (Investigator)
GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg2.5± 1.78
Patritumab Deruxtecan Up-Titration2.1± 1.09
Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors Secondary · Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months

The best percentage change in the SoD of measurable tumors is defined as the percentage change in the smallest SoD from all post-baseline tumor assessments, taking as reference the baseline SoD.

Sum of diameters (BICR)
GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg-25.66± 30.39
Patritumab Deruxtecan Up-Titration-17.48± 29.54
Sum of diameters (Investigator)
GroupValue95% CI
Patritumab Deruxtecan 5.6 mg/kg-20.84± 27.01
Patritumab Deruxtecan Up-Titration-11.46± 29.25

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected from after first dose up to 47 days post last dose, up to approximately 21 months (primary outcome data cutoff date).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Patritumab Deruxtecan 5.6 mg/kg
Serious: 90/225 (40%)
Deaths: 114/225
Patritumab Deruxtecan Up-Titration
Serious: 16/50 (32%)
Deaths: 28/50

Serious adverse events (86 terms)

ReactionSystemPatritumab Deruxtecan 5.6 …Patritumab Deruxtecan Up-T…
Disease progressionGeneral disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
PneumoniaInfections and infestations
NauseaGastrointestinal disorders
Febrile neutropeniaBlood and lymphatic system disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
SeizureNervous system disorders
Decreased appetiteMetabolism and nutrition disorders
PyrexiaGeneral disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
VomitingGastrointestinal disorders
Metastases to meningesNeoplasms benign, malignant and unspecified (incl cysts and polyps)
AstheniaGeneral disorders
FatigueGeneral disorders
MalaiseGeneral disorders
Non-cardiac chest painGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumothoraxRespiratory, thoracic and mediastinal disorders
COVID-19Infections and infestations
SepsisInfections and infestations
Septic shockInfections and infestations
StomatitisGastrointestinal disorders
AphasiaNervous system disorders
Other adverse events (51 terms — click to expand)

ReactionSystemPatritumab Deruxtecan 5.6 …Patritumab Deruxtecan Up-T…
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
FatigueGeneral disorders
Platelet count decreasedInvestigations
DiarrhoeaGastrointestinal disorders
Neutrophil count decreasedInvestigations
VomitingGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
White blood cell count decreasedInvestigations
AstheniaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Aspartate aminotransferase increasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
CoughRespiratory, thoracic and mediastinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
StomatitisGastrointestinal disorders
Alanine aminotransferase increasedInvestigations
HeadacheNervous system disorders
Weight decreasedInvestigations
NeutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Blood alkaline phosphatase increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
Oedema peripheralGeneral disorders
HypoalbuminaemiaMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
COVID-19Infections and infestations
Abdominal painGastrointestinal disorders
InsomniaPsychiatric disorders
Lymphocyte count decreasedInvestigations
MalaiseGeneral disorders
HyperglycaemiaMetabolism and nutrition disorders
HyponatraemiaMetabolism and nutrition disorders
Abdominal pain upperGastrointestinal disorders
DyspepsiaGastrointestinal disorders
DysgeusiaNervous system disorders
Blood lactate dehydrogenase increasedInvestigations

Most-reported serious reactions: Disease progression, Pneumonitis, Anaemia, Pneumonia, Nausea, Febrile neutropenia, Pleural effusion, Thrombocytopenia.

Data from ClinicalTrials.gov NCT04619004 adverse events section.

Sponsor's own description

This study is designed to evaluate the antitumor activity of patritumab deruxtecan in participants with metastatic or locally advanced NSCLC with an activating EGFR mutation (exon 19 deletion or L858R) who have received and progressed on or after at least 1 EGFR TKI and 1 platinum-based chemotherapy-containing regimen.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Third-generation EGFR and ALK inhibitors: mechanisms of resistance and management.
    Cooper AJ, Sequist LV, Lin JJ. · · 2022 · cited 382× · PMID 35534623 · DOI 10.1038/s41571-022-00639-9
  2. Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance.
    Fu K, Xie F, Wang F, Fu L. · · 2022 · cited 271× · PMID 36482474 · DOI 10.1186/s13045-022-01391-4
  3. Efficacy and Safety of Patritumab Deruxtecan (HER3-DXd) in EGFR Inhibitor-Resistant, <i>EGFR</i>-Mutated Non-Small Cell Lung Cancer.
    Jänne PA, Baik C, Su WC, Johnson ML, et al · · 2022 · cited 236× · PMID 34548309 · DOI 10.1158/2159-8290.cd-21-0715
  4. HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy.
    Yu HA, Goto Y, Hayashi H, Felip E, et al · · 2023 · cited 175× · PMID 37689979 · DOI 10.1200/jco.23.01476
  5. Antibody-drug conjugates in solid tumors: a look into novel targets.
    Criscitiello C, Morganti S, Curigliano G. · · 2021 · cited 169× · PMID 33509252 · DOI 10.1186/s13045-021-01035-z
  6. Payload diversification: a key step in the development of antibody-drug conjugates.
    Conilh L, Sadilkova L, Viricel W, Dumontet C. · · 2023 · cited 152× · PMID 36650546 · DOI 10.1186/s13045-022-01397-y
  7. Targeting cancer with antibody-drug conjugates: Promises and challenges.
    Dean AQ, Luo S, Twomey JD, Zhang B. · · 2021 · cited 145× · PMID 34291723 · DOI 10.1080/19420862.2021.1951427
  8. Antibodies to watch in 2024.
    Crescioli S, Kaplon H, Chenoweth A, Wang L, et al · · 2024 · cited 122× · PMID 38178784 · DOI 10.1080/19420862.2023.2297450

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