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)
2 other identifiers
interventional
277
15 countries
122
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2021
Longer than P75 for phase_2
122 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 29, 2020
CompletedFirst Posted
Study publicly available on registry
November 6, 2020
CompletedStudy Start
First participant enrolled
February 2, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
November 21, 2022
CompletedResults Posted
Study results publicly available
April 2, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
January 30, 2026
CompletedJanuary 23, 2026
January 1, 2026
1.8 years
October 29, 2020
March 4, 2024
January 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (8)
Duration of Response (DoR)
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)
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
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)
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)
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
- +3 more secondary outcomes
Study Arms (2)
Study Group 1: Patritumab deruxtecan 5.6 mg/kg
EXPERIMENTALStudy 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)
Study Group 2: Patritumab deruxtecan Up-Titration
EXPERIMENTALStudy 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)
Interventions
Patritumab deruxtecan will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.
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.
Eligibility Criteria
You may qualify if:
- 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)
- +6 more criteria
You may not qualify if:
- 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
- +13 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Daiichi Sankyolead
- Daiichi Sankyo Co., Ltd.collaborator
- Merck Sharp & Dohme LLCcollaborator
Study Sites (123)
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
City of Hope
Duarte, California, 91010, United States
Moores Cancer Center at the UC San Diego Health
La Jolla, California, 92093, United States
Pacific Shores Medical Group
Long Beach, California, 90813, United States
USC Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
University of California at Irvine
Orange, California, 92868, United States
Cedars Sinai
West Hollywood, California, 90048, United States
University of Colorado Denver - Anschutz Medical Campus
Aurora, Colorado, 80045, United States
Florida Cancer Specialists - South
Fort Myers, Florida, 33901, United States
AdventHealth Orlando
Orlando, Florida, 32804, United States
Memorial Healthcare System
Pembroke Pines, Florida, 33021, United States
Florida Cancer Specialist-North
St. Petersburg, Florida, 33770, United States
Florida Cancer Specialists-Panhandle
Tallahassee, Florida, 32308, United States
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, 33612, United States
Florida Cancer Specialists-East
West Palm Beach, Florida, 33401, United States
Emory University
Dunwoody, Georgia, 30338, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Maryland - Marlene and Stewart Greenebaum Cancer Center
Baltimore, Maryland, 21201, United States
Massachusetts General Hospital (MGH) - Hematology/Oncology
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center, Harvard Medical School
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Henry Ford Cancer Institute/Henry Ford Hospital
Detroit, Michigan, 48202, United States
Mount Sinai Hospital
New York, New York, 10029, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Montefiore Medical Center
The Bronx, New York, 10461, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Cleveland Clinic - Main Campus
Cleveland, Ohio, 44195, United States
Providence Portland Medical Center
Portland, Oregon, 97213, United States
Sarah Cannon Research Institute at Tennessee Oncology - Chattanooga
Chattanooga, Tennessee, 37404, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
University of Virginia Cancer Center - Emily Couric Clinical Cancer Center
Charlottesville, Virginia, 22903, United States
Virginia Cancer Specialist, PC
Fairfax, Virginia, 22031, United States
University of Washington/Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Blacktown Hospital
Blacktown, New South Wales, 2148, Australia
The Chris O'Brien Lifehouse
Camperdown, New South Wales, 2050, Australia
St George Public Hospital
Kogarah, New South Wales, 2217, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
St John of God Subiaco Hospital
Subiaco, Western Australia, 6008, Australia
Princess Alexandra Hospital
Woolloongabba, 4102, Australia
Karl Landsteiner Institut für Lungenforschung und pneumologische Onkologie c/o Klinik Floridsdorf
Vienna, 1030, Austria
Universitaire Ziekenhuis Gasthuisberg
Leuven, 3000, Belgium
MHAT Uni Hospital OOD
Panagyurishte, 4500, Bulgaria
Complex Oncological Center - Russe
Rousse, 7002, Bulgaria
MHAT Serdika
Sofia, 1303, Bulgaria
Beijing Cancer Hospital
Beijing, 100036, China
Jilin Cancer Hospital
Changchun, 130012, China
University of Electronic Science & Technology of China (UESTC) - Sichuan Cancer Hospital & Institute (Sichuan Provincial Tumor Hospital
Chengdu, 610041, China
Guangdong Academy of Medical Science (GAMS) - Guangdong Provincial Peoples Hospital
Guangzhou, 510080, China
The First Affiliated Hospital of College of Medicine Zhejiang University
Hangzhou, 310003, China
Harbin Medical University - Tumor Hospital (The Third Affiliated Hospital)
Harbin, 150081, China
General Hospital of Eastern Theater Command
Nanjing, 210002, China
Fudan University - Shanghai Cancer Center FUSCC
Shanghai, 200032, China
The First Hospital of China Medical University
Shenyang, 110001, China
Union Hospital of Tongji Medical College Huazhong University of Science and Technology
Wuhan, 430022, China
Henan Cancer Hospital
Zhengzhou, 450008, China
CHU Toulouse - Hopital Larrey
Toulouse, Haute-Garonne, 31059, France
University Hospital of Nantes - Thoracic Oncology
Nantes, Loire-Atlantique, 44000, France
Centre Leon Berard
Lyon, Rhone, 69008, France
Hopital Morvan CHU de Brest
Brest, 29609, France
Centre Hospitalier Universitaire de Grenoble
Grenoble, 38043, France
Institut Curie
Paris, 75248, France
Hopital Pontchaillou
Rennes, 35000, France
Gustave Roussy
Villejuif, 94805, France
Kliniken der Stadt Koeln gGmbH Lungenklinik Merheim
Köln, North Rhine-Westphalia, 51109, Germany
Universitaet zu Koeln - Uniklinik Koeln
Cologne, North Rhine-Westphal, 50937, Germany
LungenClinic Grosshansdorf
Großhansdorf, Schleswig-Holstein, 22927, Germany
Universitaet zu Koeln - Uniklinik Koeln
Cologne, 50931, Germany
Kliniken der Stadt Koeln gGmbH Lungenklinik Merheim
Cologne, 51109, Germany
University Cancer Center
Dresden, 01307, Germany
Azienda Ospedaliero Universitaria di Parma
Parma, Province Of Parma, 43126, Italy
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Orbassano, Turin, 10043, Italy
IRCCS - Istituto Scientifico Romagnolo per lo Studio e La Cura Dei Tumori ISRT
Meldola, 47014, Italy
Fondazione IRCCS Istituto Nazionale Tumori
Milan, 20133, Italy
Humanitas Cancer Center
Rozzano, 20089, Italy
National Cancer Center Hospital East
Kashiwa, Chiba, 277-0882, Japan
National Cancer Center Hospital
Tokyo, Chuo-ku, 104-0045, Japan
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime, 791-0280, Japan
National Hospital Organization Hokkaido Cancer Center
Sapporo, Hokkaido, 003-0804, Japan
Hyogo Cancer Center
Akashi, Hyōgo, 673-8558, Japan
National Cancer Center Hospital East
Chiba, Kashiwa-shi, 277-8577, Japan
The Cancer Institute Hospital of JFCR
Ariake, Koto, 135-8550, Japan
Sendai Kousei Hospital
Sendai, Miyagi, 980-0873, Japan
Kansai Medical University Hospital
Hirakata, Osaka, 573-1191, Japan
Kindai University Hospital
Ōsaka-sayama, Osaka, 589-8511, Japan
Shizuoka Cancer Center
Sunto-gun, Shizuoka, 411-8777, Japan
National Cancer Center Hospital
Chuo Ku, Tokyo, 104-0045, Japan
Niigata Cancer Center Hospital
Chuo Ku Niigata-shi, 961-8566, Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka, 811-1347, Japan
National Hospital Organization Hokkaido Cancer Center
Sapporo, 003-0804, Japan
Netherlands Cancer Institute
Amsterdam, 1066CX, Netherlands
National University Cancer Institute National University Hospital
Singapore, 119074, Singapore
National Cancer Centre Singapore NCCS
Singapore, 169610, Singapore
OncoCare Cancer Centre- Gleneagles Medical Centre
Singapore, 258499, Singapore
Asan Medical Center
Songpa-gu, Seoul, 05505, South Korea
Chungbuk National University Hospital
Cheongju-si, 28644, South Korea
Kyungpook National University Chilgok Hospital
Daegu, 41404, South Korea
National Cancer Center
Goyang-si, 10408, South Korea
Seoul National University Bundang Hospital
Seongnam, 13620, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Samsung Medical Center
Seoul, 06351, South Korea
The Catholic University of Korea, Seoul St. Marys Hospital
Seoul, 06591, South Korea
Hospital Universitario Virgen Macarena
Seville, Andalusia, 41009, Spain
Catalan Institute of Badalona Hospital Germans Trias i Pujol ICO
Badalona, Cataluã'a, 08916, Spain
Hospital Universitario Puerta de Hierro de Majadahonda
Majadahonda, Madrid, 28222, Spain
Hospital Universitario Vall d'Hebron
Barcelona, 08035, Spain
MD Anderson Cancer Center
Madrid, 28033, Spain
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040, Spain
Hospital Universitario 12 de Octubre
Madrid, 28041, Spain
START Madrid - Hospital Universitario HM Sanchinarro
Madrid, 28050, Spain
Hospital Regional Universitario Carlos Haya
Málaga, 29010, Spain
Hospital Clinico Universitario Lozano Bleza
Zaragoza, 50009, Spain
National Cheng Kung University Hospital
Tainan, Tai Nan Shi, 704, Taiwan
E-Da Hospital
Kaohsiung City, 824, Taiwan
Chang Gung Memorial Hospital CGMH - Kaohsiung Branch
Niaosong, 83301, Taiwan
Taichung Veterans General Hospital
Taichung, 40705, Taiwan
Chung Shan Medical University Hospital
Taichung, 420, Taiwan
National Taiwan University Hospital NTUH
Taipei, 100, Taiwan
MacKay Memorial Hospital
Taipei, 10449, Taiwan
Chang Gung Memorial Hospital - Linkou Branch
Taoyuan District, 333, Taiwan
University Hospital Birmingham NHS Trust
Birmingham, B9 5SS, United Kingdom
The Royal Marsden NHS Foundation Trust
London, E20 1JQ, United Kingdom
University College London Hospitals
London, NW12PG, United Kingdom
The Christie Hospital
Manchester, M20 4BX, United Kingdom
Related Publications (3)
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.
PMID: 38958845DERIVEDYu 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.
PMID: 37689979DERIVEDYu 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.
PMID: 37212796DERIVED
MeSH Terms
Interventions
Results Point of Contact
- Title
- Contact for Clinical Trial Information
- Organization
- Daiichi Sankyo, Inc.
Study Officials
- STUDY DIRECTOR
Medical Director
Daiichi Sankyo
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
October 29, 2020
First Posted
November 6, 2020
Study Start
February 2, 2021
Primary Completion
November 21, 2022
Study Completion
January 30, 2026
Last Updated
January 23, 2026
Results First Posted
April 2, 2024
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- 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.
- 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.
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/