HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer
- Conditions
- Non-Small Cell Lung Cancer MetastaticNon-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor
- Interventions
- Registration Number
- NCT04619004
- Lead Sponsor
- Daiichi Sankyo
- 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).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 277
Participants must meet all of the following criteria to be eligible for inclusion in this study.
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Sign and date the tissue informed consent form (ICF) and the main ICF, prior to the start of any study-specific qualification procedures.
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Male or female participants aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old).
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Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiation.
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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.
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Documentation of an EGFR-activating mutation detected from tumor tissue or blood sample: exon 19 deletion or L858R.
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At least 1 measurable lesion confirmed by BICR as per RECIST v1.1
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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.
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Eastern Cooperative Oncology Group Performance Standard of 0 or 1 at Screening.
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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
Participants meeting any exclusion criteria for this study will be excluded from this study.
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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.
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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.
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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.
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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.
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Evidence of any leptomeningeal disease.
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Evidence of clinically active spinal cord compression or brain metastases.
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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.
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Prior treatment with an anti-human epidermal growth factor receptor 3 (HER3) antibody or single-agent topoisomerase I inhibitor.
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Prior treatment with an antibody drug conjugate (ADC) that consists of any topoisomerase I inhibitor
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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.
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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.
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Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1
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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.
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Participant with any human immunodeficiency virus (HIV) infection.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Study Group 1: Patritumab deruxtecan 5.6 mg/kg Patritumab Deruxtecan (Fixed dose) 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) Study Group 2: Patritumab deruxtecan Up-Titration 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)
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR) Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months ORR is defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as a disappearance of all target lesions and PR was defined as at least a 30% decrease in the sum of diameters of target lesions based on RECIST v1.1.
- Secondary Outcome Measures
Name Time Method 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 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.
Overall Survival (OS) Death date is collected until the participant discontinues the study or up to approximately 45 months OS defined as the time from the start of study treatment to the date of death due to any cause.
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 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.
Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs) From baseline up to Day 47 post last dose 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.
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 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.
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 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.
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 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.
Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 21 months The best percentage change in the SoD of measurable tumors is defined as the percentage change in the smallest SoD from all post-baseline tumor assessments, taking as reference the baseline SoD.
Trial Locations
- Locations (118)
The Catholic University of Korea, Seoul St. Marys Hospital
🇰🇷Seoul, Korea, Republic of
Netherlands Cancer Institute
🇳🇱Amsterdam, Netherlands
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
Humanitas Cancer Center
🇮🇹Rozzano, Italy
Fondazione IRCCS Istituto Nazionale Tumori
🇮🇹Milano, Italy
National Cancer Center Hospital East
🇯🇵Chiba, Kashiwa-shi, Japan
National Cancer Center Hospital
🇯🇵Chuo Ku, Tokyo, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsuyama, Ehime, Japan
National Hospital Organization Hokkaido Cancer Center
🇯🇵Sapporo, Japan
Hyogo Cancer Center
🇯🇵Akashi, Hyogo, 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
🇯🇵Nagaizumi-chō, Shizuoka, Japan
Niigata Cancer Center Hospital
🇯🇵Chuo Ku, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Chungbuk National University Hospital
🇰🇷Cheongju-si, Korea, Republic of
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
National University Cancer Institute National University Hospital
🇸🇬Singapore, Singapore
National Cancer Centre Singapore NCCS
🇸🇬Singapore, Singapore
OncoCare Cancer Centre- Gleneagles Medical Centre
🇸🇬Singapore, Singapore
Hospital Universitario Virgen Macarena
🇪🇸Sevilla, Andalucia, 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 City, 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, 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
Fudan University - Shanghai Cancer Center FUSCC
🇨🇳Shanghai, China
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
🇺🇸Saint 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
Montefiore Medical Center
🇺🇸Bronx, New York, United States
Mount Sinai Hospital
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, 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
🇦🇹Wien, Austria
Universitaire Ziekenhuis Gasthuisberg
🇧🇪Leuven, Belgium
MHAT Uni Hospital OOD
🇧🇬Panagyurishte, Bulgaria
Complex Oncological Center - Russe
🇧🇬Russe, Bulgaria
MHAT Serdika
🇧🇬Sofia, Bulgaria
Beijing Cancer Hospital
🇨🇳Beijing, China
Jilin Cancer Hospital
🇨🇳Chang chun, 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
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
🇩🇪Koeln, Germany
Universitaet zu Koeln - Uniklinik Koeln
🇩🇪Koeln, Germany
LungenClinic Grosshansdorf
🇩🇪Großhansdorf, Schleswig-Holstein, Germany
University Cancer Center
🇩🇪Dresden, Germany