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

HERTHENA-Lung01: A Phase 2 Randomized Open-Label Study of Patritumab Deruxtecan (U3-1402) in Subjects With Previously Treated Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer (NSCLC)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Non-Small Cell Lung Cancer Metastatic; Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor
• Intervention / Treatment: Drug: Patritumab Deruxtecan (Fixed dose); Drug: Patritumab Deruxtecan (Up-Titration)

Detailed Description

This study will initially randomize participants to one of 2 arms in a 1:1 ratio to receive either a 5.6 mg/kg fixed dose regimen or an up-titration dose regimen of patritumab deruxtecan (HER3-DXd, U3-1402).

• Study Type: Interventional
• Enrollment (Actual): 277
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Woolloongabba, Australia, 4102
    • Princess Alexandra Hospital
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Blacktown Hospital
    • Camperdown, New South Wales, Australia, 2050
      • The Chris O'Brien Lifehouse
    • Kogarah, New South Wales, Australia, 2217
      • St George Public Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Subiaco, Western Australia, Australia, 6008
      • St John of God Subiaco Hospital
• Austria
  • Vienna, Austria, 1030
    • Karl Landsteiner Institut für Lungenforschung und pneumologische Onkologie c/o Klinik Floridsdorf
• Belgium
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuis Gasthuisberg
• Bulgaria
  • Panagyurishte, Bulgaria, 4500
    • MHAT Uni Hospital OOD
  • Rousse, Bulgaria, 7002
    • Complex Oncological Center - Russe
  • Sofia, Bulgaria, 1303
    • MHAT Serdika
• China
  • Beijing, China, 100036
    • Beijing Cancer Hospital
  • Changchun, China, 130012
    • Jilin Cancer Hospital
  • Chengdu, China, 610041
    • University of Electronic Science & Technology of China (UESTC) - Sichuan Cancer Hospital & Institute (Sichuan Provincial Tumor Hospital
  • Guangzhou, China, 510080
    • Guangdong Academy of Medical Science (GAMS) - Guangdong Provincial Peoples Hospital
  • Hangzhou, China, 310003
    • The First Affiliated Hospital of College of Medicine Zhejiang University
  • Harbin, China, 150081
    • Harbin Medical University - Tumor Hospital (The Third Affiliated Hospital)
  • Nanjing, China, 210002
    • General Hospital of Eastern Theater Command
  • Shanghai, China, 200032
    • Fudan University - Shanghai Cancer Center FUSCC
  • Shenyang, China, 110001
    • The First Hospital of China Medical University
  • Wuhan, China, 430022
    • Union Hospital of Tongji Medical College Huazhong University of Science and Technology
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• France
  • Brest, France, 29609
    • Hopital Morvan CHU de Brest
  • Grenoble, France, 38043
    • Centre Hospitalier Universitaire de Grenoble
  • Paris, France, 75248
    • Institut Curie
  • Rennes, France, 35000
    • Hopital Pontchaillou
  • Villejuif, France, 94805
    • Gustave Roussy
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • CHU Toulouse - Hopital Larrey
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44000
      • University Hospital of Nantes - Thoracic Oncology
  • Rhone
    • Lyon, Rhone, France, 69008
      • Centre Léon Bérard
• Germany
  • Cologne, Germany, 50931
    • Universitaet zu Koeln - Uniklinik Koeln
  • Cologne, Germany, 51109
    • Kliniken der Stadt Koeln gGmbH Lungenklinik Merheim
  • Dresden, Germany, 01307
    • University Cancer Center
  • North Rhine-Westphal
    • Cologne, North Rhine-Westphal, Germany, 50937
      • Universitaet zu Koeln - Uniklinik Koeln
  • North Rhine-Westphalia
    • Köln, North Rhine-Westphalia, Germany, 51109
      • Kliniken der Stadt Koeln gGmbH Lungenklinik Merheim
  • Schleswig-Holstein
    • Großhansdorf, Schleswig-Holstein, Germany, 22927
      • LungenClinic Grosshansdorf
• Italy
  • Meldola, Italy, 47014
    • IRCCS - Istituto Scientifico Romagnolo per lo Studio e La Cura Dei Tumori ISRT
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale Tumori
  • Rozzano, Italy, 20089
    • Humanitas Cancer Center
  • Province Of Parma
    • Parma, Province Of Parma, Italy, 43126
      • Azienda Ospedaliero Universitaria di Parma
  • Turin
    • Orbassano, Turin, Italy, 10043
      • Azienda Ospedaliero-Universitaria San Luigi Gonzaga
• Japan
  • Chuo Ku Niigata-shi, Japan, 961-8566
    • Niigata Cancer Center Hospital
  • Fukuoka, Japan, 811-1347
    • National Hospital Organization Kyushu Cancer Center
  • Sapporo, Japan, 003-0804
    • National Hospital Organization Hokkaido Cancer Center
  • Chiba
    • Kashiwa, Chiba, Japan, 277-0882
      • National Cancer Center Hospital East
  • Chuo-ku
    • Tokyo, Chuo-ku, Japan, 104-0045
      • National Cancer Center Hospital
  • Ehime
    • Matsuyama, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 003-0804
      • National Hospital Organization Hokkaido Cancer Center
  • Hyōgo
    • Akashi, Hyōgo, Japan, 673-8558
      • Hyogo Cancer Center
  • Kashiwa-shi
    • Chiba, Kashiwa-shi, Japan, 277-8577
      • National Cancer Center Hospital East
  • Koto
    • Ariake, Koto, Japan, 135-8550
      • The Cancer Institute Hospital of JFCR
  • Miyagi
    • Sendai, Miyagi, Japan, 980-0873
      • Sendai Kousei Hospital
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
      • Kansai Medical University Hospital
    • Ōsaka-sayama, Osaka, Japan, 589-8511
      • Kindai University Hospital
  • Shizuoka
    • Sunto-gun, Shizuoka, Japan, 411-8777
      • Shizuoka Cancer Center
  • Tokyo
    • Chuo Ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Netherlands
  • Amsterdam, Netherlands, 1066CX
    • Netherlands Cancer Institute
• Singapore
  • Singapore, Singapore, 119074
    • National University Cancer Institute National University Hospital
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore NCCS
  • Singapore, Singapore, 258499
    • OncoCare Cancer Centre- Gleneagles Medical Centre
• South Korea
  • Cheongju-si, South Korea, 28644
    • Chungbuk National University Hospital
  • Daegu, South Korea, 41404
    • Kyungpook National University Chilgok Hospital
  • Goyang-si, South Korea, 10408
    • National Cancer Center
  • Seongnam, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 06351
    • Samsung Medical Center
  • Seoul, South Korea, 06591
    • The Catholic University of Korea, Seoul St. Marys Hospital
  • Seoul
    • Songpa-gu, Seoul, South Korea, 05505
      • Asan Medical Center
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitario Vall d'Hebron
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center
  • Madrid, Spain, 28050
    • START Madrid - Hospital Universitario HM Sanchinarro
  • Málaga, Spain, 29010
    • Hospital Regional Universitario Carlos Haya
  • Zaragoza, Spain, 50009
    • Hospital Clinico Universitario Lozano Bleza
  • Andalusia
    • Seville, Andalusia, Spain, 41009
      • Hospital Universitario Virgen Macarena
  • Cataluã'a
    • Badalona, Cataluã'a, Spain, 08916
      • Catalan Institute of Badalona Hospital Germans Trias i Pujol ICO
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro de Majadahonda
• Taiwan
  • Kaohsiung City, Taiwan, 824
    • E-DA Hospital
  • Niaosong, Taiwan, 83301
    • Chang Gung Memorial Hospital CGMH - Kaohsiung Branch
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 420
    • Chung Shan Medical University Hospital
  • Taipei, Taiwan, 10449
    • Mackay Memorial Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital NTUH
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital - Linkou Branch
  • Tai Nan Shi
    • Tainan, Tai Nan Shi, Taiwan, 704
      • National Cheng Kung University Hospital
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • University Hospital Birmingham NHS Trust
  • London, United Kingdom, NW12PG
    • University College London Hospitals
  • London, United Kingdom, E20 1JQ
    • The Royal Marsden NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • La Jolla, California, United States, 92093
      • Moores Cancer Center at the UC San Diego Health
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
    • Orange, California, United States, 92868
      • University of California at Irvine
    • West Hollywood, California, United States, 90048
      • Cedars Sinai
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver - Anschutz Medical Campus
  • Florida
    • Fort Myers, Florida, United States, 33901
      • Florida Cancer Specialists - South
    • Orlando, Florida, United States, 32804
      • AdventHealth Orlando
    • Pembroke Pines, Florida, United States, 33021
      • Memorial Healthcare System
    • St. Petersburg, Florida, United States, 33770
      • Florida Cancer Specialist-North
    • Tallahassee, Florida, United States, 32308
      • Florida Cancer Specialists-Panhandle
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
    • West Palm Beach, Florida, United States, 33401
      • Florida Cancer Specialists-East
  • Georgia
    • Dunwoody, Georgia, United States, 30338
      • Emory University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland - Marlene and Stewart Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center, Harvard Medical School
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital (MGH) - Hematology/Oncology
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Cancer Institute/Henry Ford Hospital
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
    • The Bronx, New York, United States, 10461
      • Montefiore Medical Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic - Main Campus
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Sarah Cannon Research Institute at Tennessee Oncology - Chattanooga
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia Cancer Center - Emily Couric Clinical Cancer Center
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialist, PC
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington/Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must meet all of the following criteria to be eligible for inclusion in this study.

• Sign and date the tissue informed consent form (ICF) and the main ICF, prior to the start of any study-specific qualification procedures.
• Male or female participants aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
• Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiation.

• Documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease. Participants must have received both of the following:

  • Prior treatment with osimertinib. Participants receiving an EGFR TKI at the time of signing informed consent should continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1. Participants in South Korea known to harbor a clinically actionable genomic alteration in addition to EGFR mutation (e.g., anaplastic lymphoma kinase [ALK] or ROS1 protocol oncogene 1 [ROS1] fusion) for which treatment is available must have also received prior treatment with at least 1 approved genotype-directed therapy, unless unable (i.e., if contraindicated). No new testing for these genomic alterations (e.g., ALK or ROS1 fusion) is required for Screening.
  • Systemic therapy with at least 1 platinum-based chemotherapy regimen.
• Documentation of an EGFR-activating mutation detected from tumor tissue or blood sample: exon 19 deletion or L858R.
• At least 1 measurable lesion confirmed by BICR as per RECIST v1.1

• Consented and willing to provide required tumor tissue of sufficient quantity and of adequate tumor tissue content. Required tumor tissue can be provided as either:

  • Pretreatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy OR
  • Archival tumor tissue collected from a biopsy performed within 3 months prior to signing of the tissue consent and since progression while on or after treatment with the most recent cancer therapy regimen.
• Eastern Cooperative Oncology Group Performance Standard of 0 or 1 at Screening.

• Has adequate bone marrow reserve and organ function based on local laboratory data within 14 days prior to Cycle 1 Day 1:

  • Platelet count : ≥100,000/mm^3 or ≥100 × 10^9/L (platelet transfusions are not allowed up to 14 days prior to Cycle 1 Day 1 to meet eligibility)
  • Hemoglobin: ≥9.0 g/dL (transfusion and/or growth factor support is allowed)
  • Absolute neutrophil count: ≥1500/mm^3 or ≥1.5 × 10^9/L
  • Serum creatinine (SCr) or creatinine clearance (CrCl): SCr ≤1.5 × upper limit of normal (ULN), OR CrCl ≥30 mL/min as calculated using the Cockcroft-Gault equation or measured CrCl
  • Aspartate aminotransferase/alanine aminotransferase: ≤3 × ULN (if liver metastases are present, ≤5 × ULN)
  • Total bilirubin: ≤1.5 × ULN if no liver metastases (<3 × ULN in the presence of documented Gilbert's syndrome [unconjugated hyperbilirubinemia] or liver metastases)
  • Serum albumin: ≥2.5 g/dL
  • Prothrombin time (PT) or PT-International normalized ratio (INR) and activated partial thromboplastin time (aPTT)/PTT: ≤1.5 × ULN, except for subjects on coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator

Exclusion Criteria:

Participants meeting any exclusion criteria for this study will be excluded from this study.

• 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.
• Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening.

• Clinically severe respiratory compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:

  • Any underlying pulmonary disorder (eg, pulmonary emboli within 3 months prior to the study enrollment, severe asthma, severe chronic obstructive pulmonary disease [COPD]), restrictive lung disease, pleural effusion);
  • Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis); OR prior complete pneumonectomy.
• Is receiving chronic systemic corticosteroids dosed at >10 mg prednisone or equivalent anti-inflammatory or any form of immunosuppressive therapy prior to enrollment. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
• Evidence of any leptomeningeal disease.
• Evidence of clinically active spinal cord compression or brain metastases.

• Inadequate washout period prior to Cycle 1 Day 1, defined as:

  • Whole brain radiation therapy <14 days or stereotactic brain radiation therapy <7 days;
  • Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s) from a previous cancer treatment regimen or clinical study (other than EGFR TKI), <14 days or 5 half-lives, whichever is longer;
  • Monoclonal antibodies, other than immune checkpoint inhibitors, such as bevacizumab (anti-VEGF) and cetuximab (anti-EGFR) <28 days;
  • Immune checkpoint inhibitor therapy <21 days;
  • Major surgery (excluding placement of vascular access) <28 days;
  • Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation <28 days or palliative radiation therapy <14 days; or
  • Chloroquine or hydroxychloroquine <14 days.
• Prior treatment with an anti-human epidermal growth factor receptor 3 (HER3) antibody or single-agent topoisomerase I inhibitor.
• Prior treatment with an antibody drug conjugate (ADC) that consists of any topoisomerase I inhibitor
• Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0, Grade ≤1 or baseline. Participants with chronic Grade 2 toxicities may be eligible at the discretion of the Investigator after consultation with the Sponsor Medical Monitor or designee.

• Has history of other active malignancy within 3 years prior to enrollment, except:

  • Adequately treated non-melanoma skin cancer;
  • Superficial bladder tumors (Ta, Tis, T1);
  • Adequately treated intraepithelial carcinoma of the cervix uteri;
  • Low risk non-metastatic prostate cancer (with Gleason score <7, and following local treatment or ongoing active surveillance);
  • Any other curatively treated in situ disease.
• Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1
• Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1.
• Participant with any human immunodeficiency virus (HIV) infection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Group 1: Patritumab deruxtecan 5.6 mg/kg; Study Group 1 will be participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation randomized to receive patritumab deruxtecan 5.6 mg/kg IV every 3 weeks (Q3W)	Drug: Patritumab Deruxtecan (Fixed dose); Patritumab deruxtecan will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.; Other Names: U3-1402; HER3-DXd
Experimental: Study Group 2: Patritumab deruxtecan Up-Titration; Study Group 2 will be participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation randomized to receive patritumab deruxtecan up-titration IV every 3 weeks (Q3W)	Drug: Patritumab Deruxtecan (Up-Titration); Patritumab deruxtecan will be dosed as an intravenous (IV) infusion administered at Cycle 1, 3.2 mg/kg; Cycle 2, 4.8 mg/kg; Cycle 3 and subsequent cycles, 6.4 mg/kg administered on Day 1 of each 21-day cycle.; Other Names: U3-1402; HER3-DXd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DoR)	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.	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
Progression-free Survival (PFS)	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.	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
Objective Response Rate (ORR) as Assessed by the Investigator	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.	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
Disease Control Rate (DCR)	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.	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
Time to Tumor Response (TTR)	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.	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
Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors	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.	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
Overall Survival (OS)	OS defined as the time from the start of study treatment to the date of death due to any cause.	Death date is collected until the participant discontinues the study or up to approximately 45 months
Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)	A TEAE is defined as an adverse event (AE) with a start or worsening date during the on-treatment period. A serious AE is defined as any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event, or may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes noted. AESIs will also be assessed. Adverse events will be coded using MedDRA and will be graded using NCI-CTCAE v5.0.	From baseline up to Day 47 post last dose

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Collaborators: Merck Sharp & Dohme LLC; Daiichi Sankyo Co., Ltd.
• Investigators: Study Director: Medical Director, Daiichi Sankyo

Publications and helpful links

General Publications

• Yu HA, Goto Y, Hayashi H, Felip E, Chih-Hsin Yang J, Reck M, Yoh K, Lee SH, Paz-Ares L, Besse B, Bironzo P, Kim DW, Johnson ML, Wu YL, John T, Kao S, Kozuki T, Massarelli E, Patel J, Smit E, Reckamp KL, Dong Q, Shrestha P, Fan PD, Patel P, Sporchia A, Sternberg DW, Sellami D, Janne PA. 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. J Clin Oncol. 2023 Dec 10;41(35):5363-5375. doi: 10.1200/JCO.23.01476. Epub 2023 Sep 10.
• Yu HA, Yang JC, Hayashi H, Goto Y, Felip E, Reck M, Vigliotti M, Dong Q, Cantero F, Fan PD, Kanai M, Sternberg DW, Janne PA. HERTHENA-Lung01: a phase II study of patritumab deruxtecan (HER3-DXd) in previously treated metastatic EGFR-mutated NSCLC. Future Oncol. 2023 Jun;19(19):1319-1329. doi: 10.2217/fon-2022-1250. Epub 2023 May 22.
• Patel J, Meng J, Le H, Tanaka Y, Phani S, Salas M, Wu C, Sternberg D, Esker S, Anderson JP, Crowley A, Zhou SQ, Lieb C, Sun H, Doan QV, Santhanagopal A, Reckamp KL. Real-World Treatment Patterns and Clinical Outcomes Among Patients with Metastatic or Unresectable EGFR-Mutated Non-Small Cell Lung Cancer Previously Treated with Osimertinib and Platinum-Based Chemotherapy. Adv Ther. 2024 Aug;41(8):3299-3315. doi: 10.1007/s12325-024-02936-4. Epub 2024 Jul 3.

Study record dates

Study Major Dates

• Study Start (Actual): February 2, 2021
• Primary Completion (Actual): November 21, 2022
• Study Completion (Estimated): July 3, 2026

Study Registration Dates

• First Submitted: October 29, 2020
• First Submitted That Met QC Criteria: November 5, 2020
• First Posted (Actual): November 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 14, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Epidermal growth factor receptor; Non-Small Cell Lung Cancer Metastatic; Non-Small Cell Lung Cancer with Mutation in Epidermal Growth Factor Receptor; HER3-DXd; Patritumab Deruxtecan; U3-1402
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; patritumab deruxtecan
• Other Study ID Numbers: U31402-A-U201; 2020-000730-17 (EudraCT Number); 2024-512238-13-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No