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

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)

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 suggest that patritumab deruxtecan constitutes a promising investigational therapy for patients with EGFRm NSCLC.

Study Overview

• Status: Active, not recruiting
• Conditions: EGFR L858R; EGFR Exon 19 Deletion; Nonsquamous Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Patritumab Deruxtecan; Drug: Platinum-based chemotherapy

Detailed Description

Patritumab deruxtecan (HER3-DXd, U3-1402) is an antibody-drug conjugate (ADC) comprising an anti-HER3 mAb linked to a topoisomerase I inhibitor that is in clinical development for patients with NSCLC, metastatic breast cancer, and colorectal cancer.

The primary objective of the current study is to compare the efficacy of patritumab deruxtecan versus platinum-based chemotherapy, as measured by progression-free survival (PFS) and the key secondary endpoint of overall survival (OS), in participants with metastatic or locally advanced NSCLC with an EGFR-activating mutation (exon 19 deletion or L858R) after failure of third-generation (eg, osimertinib, lazertinib, aumolertinib, alflutinib) EGFR TKI therapy.

• Study Type: Interventional
• Enrollment (Actual): 586
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Camperdown, Australia, 2050
    • The Chris O'Brien Lifehouse
  • Kogarah, Australia, 2217
    • St George Public Hospital
  • Liverpool, Australia, 2170
    • Liverpool Hospital
  • Melbourne, Australia, 3084
    • Austin Hospital
  • Subiaco, Australia, 6008
    • St John of God Subiaco Hospital
  • Woolloongabba, Australia, 4102
    • Princess Alexandra Hospital
• Austria
  • Feldkirch, Austria, 6800
    • Landeskrankenhaus Feldkirch
  • Innsbruck, Austria, 6020
    • Medizinische Universitaet Innsbruck
  • Klagenfurt, Austria, 9020
    • Klinikum Klagenfurt Pulmologie
  • Wels, Austria, 4600
    • Klinikum Wels-Grieskirchen
  • Wien, Austria, 1210
    • Karl Landsteiner Institut fur Lungenforschung und pneumologische Onkologie c/o Klinik Floridsdorf
• Belgium
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Saint-Luc
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Mechelen, Belgium, 2800
    • Az Sint Maarten Mechelen
  • Roeselare, Belgium, 8800
    • AZ DELTA
• Canada
  • Brampton, Canada, L6R 3J7
    • William Osler Health System - Brampton Civic Hospital
• China
  • Beijing, China, 100142
    • Peking University Cancer Hospital
  • Chang chun, China, 130021
    • Jilin Cancer Hospital
  • Changsha, China, 410013
    • Hunan Cancer Hospital
  • Chengdu, China, 610041
    • University of Electronic Science Technology of China UESTC - Sichuan Cancer Hospital Institute Sichuan Provincial Tumor Hospital
  • Chibi, China, 260-0013
    • National Cancer Center Hospital East
  • Fuzhou, China, 350001
    • Fujian Medical University - Union Hospital Foochow Christian Union Hospital
  • Guangzhou, China, 510080
    • Guangdong Academy of Medical Science (GAMS) - Guangdong Provincial Peoples Hospital
  • Guangzhou, China, 510080
    • The First Affiliated Hospital Sun-Yat-Sen University
  • Haidian, China, 100191
    • Pecking University Third Hospital
  • Hangzhou, China, 310022
    • Zhejiang Cancer 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
  • Hefei, China, 230022
    • The First Affiliated Hospital - Anhui Medical University Dept of Medical Oncology
  • Henan, China, 450003
    • Henan Provincial Peoples Hospital
  • Kunming, China, 650033
    • The Second Affiliated Hospital of Kunming Medical University
  • Linyi, China, 276000
    • Lin Yi Cancer Hospital
  • Nanjing, China, 210002
    • General Hospital of Eastern Theater Command
  • Nanning, China, 530021
    • The First Affiliated Hospital of Guangxi Medical University
  • Shanghai, China, 200032
    • Fudan University - Shanghai Cancer Center FUSCC
  • Shantou, China, 515041
    • Cancer Hospital of Shantou University Medical College
  • 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
  • Wuhan, China, 430030
    • Huazhong University of Science and Technology - Tongji Medical College - Tongji Hospital Tjh
  • Xi'an, China, 710061
    • The First Affiliate Hospital of Xi'An Jiaotong University
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
  • Ürümqi, China, 830000
    • Affiliated Cancer Hospital of Xinjiang Medical University
• France
  • Brest, France, 29609
    • Hopital Morvan CHU de Brest
  • Caen, France, 14076
    • Centre Francois Baclesse
  • Caen, France, 14076 CEDEX 05
    • Centre Francois Baclesse
  • Lyon, France, 69008
    • Centre Leon Berard
  • Montpellier, France, 34298
    • Montpellier Cancer Institute ICM
  • Paris, France, 75010
    • APHP - Hôpital Saint Louis
  • Paris Cedex 05, France, 75005
    • Institut Curie
  • Pierre-Bénite, France, 69495
    • Centre hospitalier Lyon Sud
  • Rennes, France, 35000
    • Centre Hospitalier Universitaire (CHU) de Rennes - Hopital de Pontchaillou
  • Saint-Herblain, France, 44805
    • Institut de Cancrologie de lOuest ICO
  • Villejuif, France, 94805
    • Gustave Roussy
• Germany
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
  • Esslingen, Germany, 73730
    • Klinikum Esslingen GmbH
  • Frankfurt am main, Germany, 60488
    • IKF Krankenhaus Nordwest
  • Gauting, Germany, 82131
    • Asklepios Fachklinik Muenchen-Gauting
  • Gießen, Germany, 35392
    • Universitatsklinik Giessen und Marburg
  • Großhansdorf, Germany, 22927
    • LungenClinic Grosshansdorf
  • Heidelberg, Germany, 69126
    • Thoraxklinik Heidelberg gGmbH
  • Immenhausen, Germany, 34376
    • LKI Lungenfachklinik Immenhausen
  • Kempten, Germany, 87439
    • Klinikverbund Allgaeu
  • Oldenburg, Germany, 26121
    • Pius-Hospital Oldenburg
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Elizabeth Hospital
  • Hong Kong, Hong Kong, 999077
    • Prince of Wales Hospital
  • Hong Kong, Hong Kong, 00852
    • Pamela Youde Nethersole Eastern Hospital
  • Hong Kong, Hong Kong, 999077
    • University of Hong Kong/Queen Mary Hospital
• Italy
  • Bari, Italy, 70124
    • IRCCS Istituto Oncologico Giovanni Paolo II
  • Chieti, Italy, 66100
    • University G. D'Annunzio Chieti
  • Lucca, Italy, 55100
    • Ospedale San Luca
  • Milano, Italy, 20141
    • IRCCS Istituto Europeo di Oncologia
  • Milano, Italy, 20162
    • ASST Grande Ospedale Metropolitano Niguarda
  • Orbassano, Italy, 10043
    • Azienda Ospedaliero-Universitaria San Luigi Gonzaga
  • Parma, Italy, 43126
    • Azienda Ospedaliero Universitaria di Parma
  • Perugia, Italy, 06132
    • Ospedale Santa Maria Della Misericordia
  • Roma, Italy, 00144
    • IFO Regina Elena
  • Rozzano, Italy, 20089
    • IRCCS Humanitas Research Hospital
  • Varese, Italy, 21100
    • ASST Sette Laghi
• Japan
  • Akashi, Japan, 673-8558
    • Hyogo Cancer Center
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Hidaka, Japan, 350-1298
    • Saitama Medical University International Medical Center
  • Hirakata, Japan, 573-1191
    • Kansai Medical University Hospital
  • Iwakuni, Japan, 740-8510
    • Iwakuni Clinical Center
  • Izumi, Japan, 594-0073
    • Izumi City General Hospital
  • Kanazawa, Japan, 920-8641
    • Kanazawa University Hospital
  • Koto-Ku, Japan, 135-8550
    • The Cancer Institute Hospital of JFCR
  • Kumamoto, Japan, 861- 4193
    • Saiseikai Kumamoto Hospital
  • Kurashiki, Japan, 710-8602
    • Kurashiki Central Hospital
  • Kurume, Japan, 830-0011
    • Kurume University Hospital
  • Matsusaka, Japan, 515-8544
    • Matsusaka Municipal Hospital
  • Matsuyama, Japan, 791-0280
    • NHO Shikoku Cancer Center
  • Nagoya, Japan, 460-0001
    • National Hospital Organization Nagoya Medical Center
  • Niigata, Japan, 951-8566
    • Niigata Cancer Center Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Sapporo, Japan, 003-0804
    • National Hospital Organization Hokkaido Cancer Center
  • Sendai, Japan, 980-0873
    • Sendai Kousei Hospital
  • Tokyo, Japan, 113-8677
    • Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
  • Toyoake, Japan, 470-1192
    • Fujita Health University Hospital
  • Wakayama, Japan, 641-8509
    • Wakayama Medical University Hospital
  • Ōsaka-sayama, Japan, 589-8511
    • Kindai University Hospital
• Korea, Republic of
  • Cheongju-si, Korea, Republic of, 28644
    • Chungbuk National University Hospital
  • Goyang, Korea, Republic of, 10323
    • National Cancer Center
  • Seongnam, Korea, Republic of, 463-707
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 135-710
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea, Seoul St. Marys Hospital
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Netherlands Cancer Institute
  • Arnhem, Netherlands, 6815 AD
    • Rijnstate Ziekenhuis
  • Harderwijk, Netherlands, 3844 DG
    • St. Jansdal ziekenhuis
  • Leiden, Netherlands, 2333ZA
    • Leiden University Medical Center
  • Rotterdam, Netherlands, 3015 CD
    • Erasmus MC
  • Utrecht, Netherlands, 3584 CX
    • University Medical Center Utrecht
• Norway
  • Nordbyhagen, Norway, 1478
    • Akershus University Hospital
  • Oslo, Norway, 0379
    • Oslo University Hospital-The Norwegian Radium Hospital
  • Stavanger, Norway, 8100
    • Stavanger University Hospital
• Poland
  • Białystok, Poland, 15-450
    • II Klinika Chorob Pluc i Gruzlicy
  • Lublin, Poland, 20-250
    • Onko-Centrum Sp. z o.o.
  • Poznań, Poland, 60-693
    • Med Polonia Sp. z o.o.
• Portugal
  • Lisboa, Portugal, 1400-038
    • Centro Clinico Champalimaud
  • Lisbon, Portugal, 1908-072
    • Instituto Portugues de Oncologio de Lisboa
  • Porto, Portugal, 4099-001
    • Centro Hospitalar Universitário do Porto - Hospital de Santo Antonio
  • Porto, Portugal, 4434-502
    • Centro Hospitalar de Vila Nova de Gaia - Espinho
• Singapore
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hospital
  • Singapore, Singapore, 119074
    • National University Cancer Institute National University Hospital
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore NCCS
  • Singapore, Singapore, 329563
    • Icon Cancer Centre
• Spain
  • A Coruña, Spain, 15006
    • Hospital Teresa Herrera C.H.U.A.C.
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Las Palmas De Gran Canaria, Spain, 35016
    • Complejo Hospitalario Materno-Insular - Hospital Insular de Gran Canaria
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon
  • Madrid, Spain, 28033
    • MD Anderson Cancer Center
  • Málaga, Spain, 29010
    • Hospital Regional Universitario Malaga
  • Santander, Spain, 39120
    • Hospital Univeritario Marques de Valdecilla
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Sevilla, Spain, 41071
    • Hospital Universitario Virgen Macarena
• Switzerland
  • Chur, Switzerland, 7000
    • Kantonsspital Graubuenden - Hauptstandort
  • Winterthur, Switzerland, 8400
    • Kantonsspital Winterthur KSW
• Taiwan
  • Kaohsiung City, Taiwan, 824
    • E-DA hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital NCKUH
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital NTUH
  • Taoyuan, Taiwan, 333
    • Chang Gung Memorial Hospital-Linkou Branch
• United Kingdom
  • Birmingham, United Kingdom, B9 5SS
    • University Hospital Birmingham NHS Trust
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Leeds, United Kingdom, LS9 7TF
    • Leeds Cancer Centre
  • Leicester, United Kingdom, LE15WW
    • University Hospitals of Leicester
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust
  • London, United Kingdom, EC1A 7BE
    • Barts and The London NHS Trust - St Bartholomew s hospital - PET CT Centre
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden Hospital NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie Hospital
  • Wolverhampton, United Kingdom, WV10 0QP
    • The Royal Wolverhampton NHS Trust
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Oncology and Hematology LLC
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • La Jolla, California, United States, 92037
      • Scripps MD Anderson Cancer Center
    • La Jolla, California, United States, 92037
      • Moores Cancer Center at the UC San Diego Health
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
    • Vallejo, California, United States, 94589
      • Kaiser Permanente - Vallejo Medical Center
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
  • Florida
    • Port Charlotte, Florida, United States, 33980
      • Sarah Cannon/Florida Cancer Specialists - FCS South
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Idaho
    • Boise, Idaho, United States, 83712
      • St Luke's Cancer Institute
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • American Oncology Partners of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Manahawkin, New Jersey, United States, 08050
      • Hackensack Meridian Health-Southern Ocean Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75235
      • University of Texas Southwestern Medical Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion 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

Exclusion 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

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: Patritumab deruxtecan; Participants who will be randomized to receive patritumab deruxtecan (HER3-DXd) 5.6 mg/kg q3W.	Drug: Patritumab Deruxtecan; Intravenous administration, 5.6 mg/kg every 3 weeks (q3W); Other Names: U3-1402; HER3-DXd
Active Comparator: Platinum-based chemotherapy; Participants who will be randomized to receive platinum-based chemotherapy for 4 cycles: pemetrexed plus either cisplatin or carboplatin. Participants without disease progression after 4 cycles of platinum plus pemetrexed therapy may continue treatment with maintenance pemetrexed with no restriction on the number of cycles.	Drug: Platinum-based chemotherapy; Intravenous, pemetrexed 500 mg/m^2 plus either cisplatin (75 mg/m^2) or carboplatin (target area under the plasma concentration time curve of 5 [AUC5] by using the Calvert formula) q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Based on RECIST v1.1	Progression-free survival (PFS) is defined as the time from the date of randomization to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause.	Baseline up to approximately 49 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall survival (OS) is defined as the time from the date of randomization to the date of death due to any cause.	Baseline up to approximately 49 months
Progression-free Survival (PFS) as Assessed by Investigator Review Based on RECIST v1.1	Progression-free survival (PFS) is defined as the time from the date of randomization to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause.	Baseline up to approximately 49 months
Progression-free Survival (PFS) as Assessed by Local Standard Clinical Practice	Progression-free survival (PFS) by local standard clinical practice is defined as the time from date of randomization to the documented progression on the first new anticancer therapy (if administered) or death due to any cause, whichever occurred first.	Baseline up to approximately 49 months
Mean Change from Baseline in Non-small Cell Lung Cancer - Symptom Assessment Questionnaire	The NSCLC-SAQ will assess disease-related symptom change in patients with NSCLC.	Baseline up to approximately 49 months
Mean Change from Baseline in Patient's Global Impression of Change	The PGI-C is a 7-point scale depicting a participant's rating of overall improvement.	Baseline up to approximately 49 months
Mean Change from Baseline in Patient's Global Impression of Severity	The PGI-S is a one-item questionnaire that contains six response options.	Baseline up to approximately 49 months
Mean Change from Baseline in Patient's Global Impression of Treatment Tolerability	The PGI-TT will capture the patient's overall impression of treatment tolerability.	Baseline up to approximately 49 months
Mean Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)	The EORTC-QLQ-C30 will assess the patient's overall quality of life (QoL).	Baseline up to approximately 49 months
Mean Change from Baseline in EuroQol Questionnaire-5 dimensions-5 levels (EQ-5D-5L)	The EQ-5D-5L is a standardized instrument that will be used for measuring generic health status required for health technology assessments.	Baseline up to approximately 49 months
Percentage of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)	The immunogenicity of patritumab deruxtecan will be confirmed by assessing the anti-drug antibodies.	Baseline up to approximately 49 months
Percentage of Participants Who Have Treatment-emergent ADA	The immunogenicity of patritumab deruxtecan will be confirmed by assessing the anti-drug antibodies.	Baseline up to approximately 49 months
Objective Response Rate (ORR) as Assessed by BICR and Investigator Review Based on RECIST v1.1	Objective response rate (ORR) is defined as the proportion of participants who have a confirmed best overall response (BOR) of complete response (CR) or partial response (PR).	Baseline up to approximately 49 months
Duration of Response (DoR) as Assessed by BICR and Investigator Review Based on RECIST v1.1	Duration of response (DoR) is defined as the time from the first documentation of objective response (CR or PR) to the earlier of the dates of the first documentation of objective progression of disease or death due to any cause.	Baseline up to approximately 49 months
Clinical Benefit Rate (CBR) as Assessed by BICR and Investigator Review Based on RECIST v1.1	Clinical benefit rate (CBR) will be assessed by BICR and Investigator based on RECIST v1.1. CBR is defined as the proportion of participants who have a confirmed BOR of CR, PR, or stable disease (SD) that lasts for at least 180 days.	Baseline up to approximately 49 months
Disease Control Rate (DCR) as Assessed by BICR and Investigator Review Based on RECIST v1.1	Disease control rate (DCR) is defined as the proportion of participants who have a confirmed BOR of CR, PR, or SD.	Baseline up to approximately 49 months
Time to Response (TTR) as Assessed by BICR and Investigator Review Based on RECIST v1.1	Time to response (TTR) is defined as the time from the date of randomization to the date of the first documentation of response (CR or PR) that is subsequently confirmed.	Baseline up to approximately 49 months
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	TEAEs will be graded by using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.	Baseline up to approximately 49 months
Intracranial PFS as Assessed by BICR	Intracranial PFS is defined as the time from the date of randomization to the earlier of the dates of the first documented radiographic intracranial disease progression or death, whichever comes first, as assessed by BICR per CNS-RECIST, in participants with CNS lesion(s) at baseline by BICR per CNS-RECIST.	Baseline up to approximately 49 months

Collaborators and Investigators

• Sponsor: Daiichi Sankyo
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Global Clinical Leader, Daiichi Sankyo; Study Chair: Clinical Scientist, Daiichi Sankyo

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2022
• Primary Completion (Actual): May 31, 2024
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 15, 2022
• First Submitted That Met QC Criteria: April 20, 2022
• First Posted (Actual): April 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 29, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: HER3-DXd; U3-1402; Nonsquamous Non-small Cell Lung Cancer; EGFR L858R; EGFR exon 19 deletion; Patritumab deruxtecan
• 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; Patritumab deruxtecan
• Other Study ID Numbers: U31402-A-U301; 2021-005879-40 (EudraCT Number); jRCT 2021220002 (Other Identifier: JAPIC)

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