Clinical trial NCT04619004: HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer Metastatic
Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor
Keywords: Non-Small Cell Lung Cancer Metastatic
Non-Small Cell Lung Cancer with Mutation in Epidermal Growth Factor Receptor
Epidermal growth factor receptor
HER3-DXd
Patritumab Deruxtecan
U3-1402
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: Daiichi Sankyo Co., Ltd.
name: Merck Sharp & Dohme LLC
First posted: 2020-11-06
Enrollment: 277
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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:

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

* Any previous histologic or cytologic evidence of small cell OR combined small cell/non-small cell disease in the archival tumor tissue or pretreatment tumor biopsy.
* Any history of interstitial lung disease (including pulmonary fibrosis or radiation pneumonitis), has current interstitial lung disease (ILD), or is suspected to have such disease by imaging during screening.
* Clinically severe respiratory compromise (based on Investigator's assessment) resulting from intercurrent pulmonary illnesses including, but not limited to:

  * Any underlying pulmonary disorder (eg, pulmonary emboli within 3 months prior to the study enrollment, severe asthma, severe chronic obstructive pulmonary disease \[COPD\]), restrictive lung disease, pleural effusion);
  * Any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis); OR prior complete pneumonectomy.
* Is receiving chronic systemic corticosteroids dosed at \>10 mg prednisone or equivalent anti-inflammatory or any form of immunosuppressive therapy prior to enrollment. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.
* Evidence of any leptomeningeal disease.
* Evidence of clinically active spinal cord compression or brain metastases.
* Inadequate washout period prior to Cycle 1 Day 1, defined as:

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

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

Primary outcomes:
measure: Objective Response Rate (ORR) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: 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:
measure: Duration of Response (DoR)
timeFrame: 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
measure: Progression-free Survival (PFS)
timeFrame: 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
measure: Objective Response Rate (ORR) as Assessed by the Investigator
timeFrame: 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
measure: Disease Control Rate (DCR)
timeFrame: 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
measure: Time to Tumor Response (TTR)
timeFrame: 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
measure: Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors
timeFrame: 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
measure: Overall Survival (OS)
timeFrame: Death date is collected until the participant discontinues the study or up to approximately 45 months
measure: Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)
timeFrame: From baseline up to Day 47 post last dose
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: Moores Cancer Center at the UC San Diego Health
state: California
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Orange
country: United States
facility: University of California at Irvine
state: California
city: West Hollywood
country: United States
facility: Cedars Sinai
state: California
city: Aurora
country: United States
facility: University of Colorado Denver - Anschutz Medical Campus
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists - South
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Healthcare System
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialist-North
state: Florida
city: Tallahassee
country: United States
facility: Florida Cancer Specialists-Panhandle
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists-East
state: Florida
city: Dunwoody
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland - Marlene and Stewart Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital (MGH) - Hematology/Oncology
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center, Harvard Medical School
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Cancer Institute/Henry Ford Hospital
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Hospital
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic - Main Campus
state: Ohio
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Chattanooga
country: United States
facility: Sarah Cannon Research Institute at Tennessee Oncology - Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center - Emily Couric Clinical Cancer Center
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialist, PC
state: Virginia
city: Seattle
country: United States
facility: University of Washington/Seattle Cancer Care Alliance
state: Washington
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: Camperdown
country: Australia
facility: The Chris O'Brien Lifehouse
state: New South Wales
city: Kogarah
country: Australia
facility: St George Public Hospital
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Subiaco
country: Australia
facility: St John of God Subiaco Hospital
state: Western Australia
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Wien
country: Austria
facility: Karl Landsteiner Institut fÃ¼r Lungenforschung und pneumologische Onkologie c/o Klinik Floridsdorf
city: Leuven
country: Belgium
facility: Universitaire Ziekenhuis Gasthuisberg
city: Panagyurishte
country: Bulgaria
facility: MHAT Uni Hospital OOD
city: Russe
country: Bulgaria
facility: Complex Oncological Center - Russe
city: Sofia
country: Bulgaria
facility: MHAT Serdika
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Chang chun
country: China
facility: Jilin Cancer Hospital
city: Chengdu
country: China
facility: University of Electronic Science & Technology of China (UESTC) - Sichuan Cancer Hospital & Institute (Sichuan Provincial Tumor Hospital
city: Guangzhou
country: China
facility: Guangdong Academy of Medical Science (GAMS) - Guangdong Provincial Peoples Hospital
city: Hangzhou
country: China
facility: The First Affiliated Hospital of College of Medicine Zhejiang University
city: Harbin
country: China
facility: Harbin Medical University - Tumor Hospital (The Third Affiliated Hospital)
city: Nanjing
country: China
facility: General Hospital of Eastern Theater Command
city: Shanghai
country: China
facility: Fudan University - Shanghai Cancer Center FUSCC
city: Shenyang
country: China
facility: The First Hospital of China Medical University
city: Wuhan
country: China
facility: Union Hospital of Tongji Medical College Huazhong University of Science and Technology
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Toulouse
country: France
facility: CHU Toulouse - Hopital Larrey
state: Haute-Garonne
city: Nantes
country: France
facility: University Hospital of Nantes - Thoracic Oncology
state: Loire-Atlantique
city: Lyon
country: France
facility: Centre Leon Berard
state: Rhone
city: Brest
country: France
facility: Hopital Morvan CHU de Brest
city: Grenoble
country: France
facility: Centre Hospitalier Universitaire de Grenoble
city: Paris
country: France
facility: Institut Curie
city: Rennes
country: France
facility: Hopital Pontchaillou
city: Villejuif
country: France
facility: Gustave Roussy
city: Koeln
country: Germany
facility: Kliniken der Stadt Koeln gGmbH Lungenklinik Merheim
state: Nordrhein-Westfalen
city: Koeln
country: Germany
facility: Universitaet zu Koeln - Uniklinik Koeln
state: North Rhine-Westphal
city: Großhansdorf
country: Germany
facility: LungenClinic Grosshansdorf
state: Schleswig-Holstein
city: Dresden
country: Germany
facility: University Cancer Center
city: Koeln
country: Germany
facility: Universitaet zu Koeln - Uniklinik Koeln
city: Koeln
country: Germany
facility: Kliniken der Stadt Koeln gGmbH Lungenklinik Merheim
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
state: Province Of Parma
city: Orbassano
country: Italy
facility: Azienda Ospedaliero-Universitaria San Luigi Gonzaga
state: Turin
city: Meldola
country: Italy
facility: IRCCS - Istituto Scientifico Romagnolo per lo Studio e La Cura Dei Tumori ISRT
city: Milano
country: Italy
facility: Fondazione IRCCS Istituto Nazionale Tumori
city: Rozzano
country: Italy
facility: Humanitas Cancer Center
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
state: Chuo-ku
city: Matsuyama
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Sapporo
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Hokkaido
city: Akashi
country: Japan
facility: Hyogo Cancer Center
state: Hyogo
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
state: Kashiwa-shi
city: Ariake
country: Japan
facility: The Cancer Institute Hospital of JFCR
state: Koto
city: Sendai
country: Japan
facility: Sendai Kousei Hospital
state: Miyagi
city: Hirakata
country: Japan
facility: Kansai Medical University Hospital
state: Osaka
city: Ōsaka-sayama
country: Japan
facility: Kindai University Hospital
state: Osaka
city: Nagaizumi-chō
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Chuo Ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Chuo Ku
country: Japan
facility: Niigata Cancer Center Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Sapporo
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Chilgok Hospital
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St. Marys Hospital
city: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: Singapore
country: Singapore
facility: National University Cancer Institute National University Hospital
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore NCCS
city: Singapore
country: Singapore
facility: OncoCare Cancer Centre- Gleneagles Medical Centre
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
state: Andalucia
city: Badalona
country: Spain
facility: Catalan Institute of Badalona Hospital Germans Trias i Pujol ICO
state: Cataluã'a
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro de Majadahonda
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: MD Anderson Cancer Center
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: START Madrid - Hospital Universitario HM Sanchinarro
city: Málaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Bleza
city: Tainan City
country: Taiwan
facility: National Cheng Kung University Hospital
state: Tai Nan Shi
city: Kaohsiung City
country: Taiwan
facility: E-Da Hospital
city: Niaosong
country: Taiwan
facility: Chang Gung Memorial Hospital CGMH - Kaohsiung Branch
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital NTUH
city: Taipei
country: Taiwan
facility: MacKay Memorial Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou Branch
city: Birmingham
country: United Kingdom
facility: University Hospital Birmingham NHS Trust
city: London
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
city: London
country: United Kingdom
facility: University College London Hospitals
city: Manchester
country: United Kingdom
facility: The Christie Hospital
Study officials:
affiliation: Daiichi Sankyo
name: Medical Director
role: STUDY_DIRECTOR
References: