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

NCT ID: NCT04619004

Last Updated: 2026-01-23

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 277 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-02-02
• Study Completion Date: 2026-01-30

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.

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).

Conditions

Non-Small Cell Lung Cancer Metastatic; Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Patritumab Deruxtecan (Fixed dose)

Intervention Type: DRUG

Patritumab deruxtecan will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.

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)

Group Type: EXPERIMENTAL

Patritumab Deruxtecan (Up-Titration)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

U3-1402; HER3-DXd; U3-1402; HER3-DXd

Eligibility Criteria

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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo Co., Ltd.

INDUSTRY

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

City of Hope

Duarte, California, United States

Moores Cancer Center at the UC San Diego Health

La Jolla, California, United States

Pacific Shores Medical Group

Long Beach, California, United States

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States

University of California at Irvine

Orange, California, United States

Cedars Sinai

West Hollywood, California, United States

University of Colorado Denver - Anschutz Medical Campus

Aurora, Colorado, United States

Florida Cancer Specialists - South

Fort Myers, Florida, United States

AdventHealth Orlando

Orlando, Florida, United States

Memorial Healthcare System

Pembroke Pines, Florida, United States

Florida Cancer Specialist-North

St. Petersburg, Florida, United States

Florida Cancer Specialists-Panhandle

Tallahassee, Florida, United States

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Florida Cancer Specialists-East

West Palm Beach, Florida, United States

Emory University

Dunwoody, Georgia, United States

Northwestern University

Chicago, Illinois, United States

University of Maryland - Marlene and Stewart Greenebaum Cancer Center

Baltimore, Maryland, United States

Massachusetts General Hospital (MGH) - Hematology/Oncology

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center, Harvard Medical School

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Henry Ford Cancer Institute/Henry Ford Hospital

Detroit, Michigan, United States

Mount Sinai Hospital

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Cleveland Clinic - Main Campus

Cleveland, Ohio, United States

Providence Portland Medical Center

Portland, Oregon, United States

Sarah Cannon Research Institute at Tennessee Oncology - Chattanooga

Chattanooga, Tennessee, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

University of Virginia Cancer Center - Emily Couric Clinical Cancer Center

Charlottesville, Virginia, United States

Virginia Cancer Specialist, PC

Fairfax, Virginia, United States

University of Washington/Seattle Cancer Care Alliance

Seattle, Washington, United States

Blacktown Hospital

Blacktown, New South Wales, Australia

The Chris O'Brien Lifehouse

Camperdown, New South Wales, Australia

St George Public Hospital

Kogarah, New South Wales, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

St John of God Subiaco Hospital

Subiaco, Western Australia, Australia

Princess Alexandra Hospital

Woolloongabba, , Australia

Karl Landsteiner Institut für Lungenforschung und pneumologische Onkologie c/o Klinik Floridsdorf

Vienna, , Austria

Universitaire Ziekenhuis Gasthuisberg

Leuven, , Belgium

MHAT Uni Hospital OOD

Panagyurishte, , Bulgaria

Complex Oncological Center - Russe

Rousse, , Bulgaria

MHAT Serdika

Sofia, , Bulgaria

Beijing Cancer Hospital

Beijing, , China

Jilin Cancer Hospital

Changchun, , China

University of Electronic Science & Technology of China (UESTC) - Sichuan Cancer Hospital & Institute (Sichuan Provincial Tumor Hospital

Chengdu, , China

Guangdong Academy of Medical Science (GAMS) - Guangdong Provincial Peoples Hospital

Guangzhou, , China

The First Affiliated Hospital of College of Medicine Zhejiang University

Hangzhou, , China

Harbin Medical University - Tumor Hospital (The Third Affiliated Hospital)

Harbin, , China

General Hospital of Eastern Theater Command

Nanjing, , China

Fudan University - Shanghai Cancer Center FUSCC

Shanghai, , China

The First Hospital of China Medical University

Shenyang, , China

Union Hospital of Tongji Medical College Huazhong University of Science and Technology

Wuhan, , China

Henan Cancer Hospital

Zhengzhou, , China

CHU Toulouse - Hopital Larrey

Toulouse, Haute-Garonne, France

University Hospital of Nantes - Thoracic Oncology

Nantes, Loire-Atlantique, France

Centre Leon Berard

Lyon, Rhone, France

Hopital Morvan CHU de Brest

Brest, , France

Centre Hospitalier Universitaire de Grenoble

Grenoble, , France

Institut Curie

Paris, , France

Hopital Pontchaillou

Rennes, , France

Gustave Roussy

Villejuif, , France

Kliniken der Stadt Koeln gGmbH Lungenklinik Merheim

Köln, North Rhine-Westphalia, Germany

Universitaet zu Koeln - Uniklinik Koeln

Cologne, North Rhine-Westphal, Germany

LungenClinic Grosshansdorf

Großhansdorf, Schleswig-Holstein, Germany

Universitaet zu Koeln - Uniklinik Koeln

Cologne, , Germany

Kliniken der Stadt Koeln gGmbH Lungenklinik Merheim

Cologne, , Germany

University Cancer Center

Dresden, , Germany

Azienda Ospedaliero Universitaria di Parma

Parma, Province Of Parma, Italy

Azienda Ospedaliero-Universitaria San Luigi Gonzaga

Orbassano, Turin, Italy

IRCCS - Istituto Scientifico Romagnolo per lo Studio e La Cura Dei Tumori ISRT

Meldola, , Italy

Fondazione IRCCS Istituto Nazionale Tumori

Milan, , Italy

Humanitas Cancer Center

Rozzano, , Italy

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

National Cancer Center Hospital

Tokyo, Chuo-ku, Japan

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, Japan

National Hospital Organization Hokkaido Cancer Center

Sapporo, Hokkaido, Japan

Hyogo Cancer Center

Akashi, Hyōgo, Japan

National Cancer Center Hospital East

Chiba, Kashiwa-shi, Japan

The Cancer Institute Hospital of JFCR

Ariake, Koto, Japan

Sendai Kousei Hospital

Sendai, Miyagi, Japan

Kansai Medical University Hospital

Hirakata, Osaka, Japan

Kindai University Hospital

Ōsaka-sayama, Osaka, Japan

Shizuoka Cancer Center

Sunto-gun, Shizuoka, Japan

National Cancer Center Hospital

Chuo Ku, Tokyo, Japan

Niigata Cancer Center Hospital

Chuo Ku Niigata-shi, , Japan

National Hospital Organization Kyushu Cancer Center

Fukuoka, , Japan

National Hospital Organization Hokkaido Cancer Center

Sapporo, , Japan

Netherlands Cancer Institute

Amsterdam, , Netherlands

National University Cancer Institute National University Hospital

Singapore, , Singapore

National Cancer Centre Singapore NCCS

Singapore, , Singapore

OncoCare Cancer Centre- Gleneagles Medical Centre

Singapore, , Singapore

Asan Medical Center

Songpa-gu, Seoul, South Korea

Chungbuk National University Hospital

Cheongju-si, , South Korea

Kyungpook National University Chilgok Hospital

Daegu, , South Korea

National Cancer Center

Goyang-si, , South Korea

Seoul National University Bundang Hospital

Seongnam, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea, Seoul St. Marys Hospital

Seoul, , South Korea

Hospital Universitario Virgen Macarena

Seville, Andalusia, Spain

Catalan Institute of Badalona Hospital Germans Trias i Pujol ICO

Badalona, Cataluã'a, Spain

Hospital Universitario Puerta de Hierro de Majadahonda

Majadahonda, Madrid, Spain

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

MD Anderson Cancer Center

Madrid, , Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

START Madrid - Hospital Universitario HM Sanchinarro

Madrid, , Spain

Hospital Regional Universitario Carlos Haya

Málaga, , Spain

Hospital Clinico Universitario Lozano Bleza

Zaragoza, , Spain

National Cheng Kung University Hospital

Tainan, Tai Nan Shi, Taiwan

E-Da Hospital

Kaohsiung City, , Taiwan

Chang Gung Memorial Hospital CGMH - Kaohsiung Branch

Niaosong, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

Chung Shan Medical University Hospital

Taichung, , Taiwan

National Taiwan University Hospital NTUH

Taipei, , Taiwan

MacKay Memorial Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital - Linkou Branch

Taoyuan District, , Taiwan

University Hospital Birmingham NHS Trust

Birmingham, , United Kingdom

The Royal Marsden NHS Foundation Trust

London, , United Kingdom

University College London Hospitals

London, , United Kingdom

The Christie Hospital

Manchester, , United Kingdom

Countries

United States; Australia; Austria; Belgium; Bulgaria; China; France; Germany; Italy; Japan; Netherlands; Singapore; South Korea; Spain; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37689979 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37212796 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2020-000730-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U31402-A-U201

Identifier Type: -

Identifier Source: org_study_id