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

Non-Small Cell Lung Cancer Metastatic Clinical Trial

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04619004
• Other study ID #: U31402-A-U201
• Secondary ID: 2020-000730-17
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 2, 2021
• Est. completion date: November 1, 2024

Study information

• Verified date: May 2024
• Source: Daiichi Sankyo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 277
• Est. completion date: November 1, 2024
• Est. primary completion date: November 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer Metastatic
• Non-Small Cell Lung Cancer With Mutation in Epidermal Growth Factor Receptor

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Australia	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
Austria	Karl Landsteiner Institut für Lungenforschung und pneumologische Onkologie c/o Klinik Floridsdorf	Wien
Belgium	Universitaire Ziekenhuis Gasthuisberg	Leuven
Bulgaria	MHAT Uni Hospital OOD	Panagyurishte
Bulgaria	Complex Oncological Center - Russe	Russe
Bulgaria	MHAT Serdika	Sofia
China	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	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
France	Hopital Morvan CHU de Brest	Brest
France	Centre Hospitalier Universitaire de Grenoble	Grenoble
France	Centre Leon Berard	Lyon	Rhone
France	University Hospital of Nantes - Thoracic Oncology	Nantes	Loire-Atlantique
France	Institut Curie	Paris
France	Hopital Pontchaillou	Rennes
France	CHU Toulouse - Hopital Larrey	Toulouse	Haute-Garonne
France	Gustave Roussy	Villejuif
Germany	University Cancer Center	Dresden
Germany	LungenClinic Grosshansdorf	Großhansdorf	Schleswig-Holstein
Germany	Kliniken der Stadt Koeln gGmbH Lungenklinik Merheim	Köln	Nordrhein-Westfalen
Germany	Kliniken der Stadt Koeln gGmbH Lungenklinik Merheim	Koeln
Germany	Universitaet zu Koeln - Uniklinik Koeln	Koeln
Germany	Universitaet zu Koeln - Uniklinik Koeln	Koeln	North Rhine-Westphal
Italy	IRCCS - Istituto Scientifico Romagnolo per lo Studio e La Cura Dei Tumori ISRT	Meldola
Italy	Fondazione IRCCS Istituto Nazionale Tumori	Milano
Italy	Azienda Ospedaliero-Universitaria San Luigi Gonzaga	Orbassano	Turin
Italy	Azienda Ospedaliero Universitaria di Parma	Parma	Province Of Parma
Italy	Humanitas Cancer Center	Rozzano
Japan	Hyogo Cancer Center	Akashi	Hyogo
Japan	The Cancer Institute Hospital of JFCR	Ariake	Koto
Japan	National Cancer Center Hospital East	Chiba	Kashiwa-shi
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	Kansai Medical University Hospital	Hirakata	Osaka
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama	Ehime
Japan	Kindai University Hospital	Osaka-sayama	Osaka
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo
Japan	National Hospital Organization Hokkaido Cancer Center	Sapporo	Hokkaido
Japan	Sendai Kousei Hospital	Sendai	Miyagi
Japan	Shizuoka Cancer Center	Sunto-gun	Shizuoka
Japan	National Cancer Center Hospital	Tokyo	Chuo-ku
Korea, Republic of	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	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Marys Hospital	Seoul
Korea, Republic of	Asan Medical Center	Songpa-gu	Seoul
Netherlands	Netherlands Cancer Institute	Amsterdam
Singapore	National Cancer Centre Singapore NCCS	Singapore
Singapore	National University Cancer Institute National University Hospital	Singapore
Singapore	OncoCare Cancer Centre- Gleneagles Medical Centre	Singapore
Spain	Catalan Institute of Badalona Hospital Germans Trias i Pujol ICO	Badalona	Cataluã'a
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	MD Anderson Cancer Center	Madrid
Spain	START Madrid - Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Puerta de Hierro de Majadahonda	Majadahonda	Madrid
Spain	Hospital Regional Universitario Carlos Haya	Málaga
Spain	Hospital Universitario Virgen Macarena	Sevilla	Andalucia
Spain	Hospital Clinico Universitario Lozano Bleza	Zaragoza
Taiwan	E-Da Hospital	Kaohsiung City
Taiwan	Chang Gung Memorial Hospital CGMH - Kaohsiung Branch	Niaosong
Taiwan	Chang Gung Memorial Hospital CGMH - Kaohsiung Branch	Niaosong	Gao Xiong Shi
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan City	Tai Nan Shi
Taiwan	MacKay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital NTUH	Taipei
Taiwan	Chang Gung Memorial Hospital - Linkou Branch	Taoyuan
United Kingdom	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 States	University of Colorado Denver - Anschutz Medical Campus	Aurora	Colorado
United States	University of Maryland - Marlene and Stewart Greenebaum Cancer Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center, Harvard Medical School	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital (MGH) - Hematology/Oncology	Boston	Massachusetts
United States	Montefiore Medical Center	Bronx	New York
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia Cancer Center - Emily Couric Clinical Cancer Center	Charlottesville	Virginia
United States	Sarah Cannon Research Institute at Tennessee Oncology - Chattanooga	Chattanooga	Tennessee
United States	Northwestern University	Chicago	Illinois
United States	Cleveland Clinic - Main Campus	Cleveland	Ohio
United States	Henry Ford Cancer Institute/Henry Ford Hospital	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	Emory University	Dunwoody	Georgia
United States	Virginia Cancer Specialist, PC	Fairfax	Virginia
United States	Florida Cancer Specialists - South	Fort Myers	Florida
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
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	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	University of California at Irvine	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Memorial Healthcare System	Pembroke Pines	Florida
United States	Providence Portland Medical Center	Portland	Oregon
United States	Florida Cancer Specialist-North	Saint Petersburg	Florida
United States	University of Washington/Seattle Cancer Care Alliance	Seattle	Washington
United States	Florida Cancer Specialists-Panhandle	Tallahassee	Florida
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	Cedars Sinai	West Hollywood	California
United States	Florida Cancer Specialists-East	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo	Daiichi Sankyo Co., Ltd.

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  China,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Singapore,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Duration of Response (DoR)	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.	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	Progression-free Survival (PFS)	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.	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	Objective Response Rate (ORR) as Assessed by the Investigator	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.	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
Secondary	Disease Control Rate (DCR)	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.	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	Time to Tumor Response (TTR)	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.	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	Best Percentage Change in the Sum of Diameters (SoD) of Measurable Tumors	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.	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	Overall Survival (OS)	OS defined as the time from the start of study treatment to the date of death due to any cause.	Death date is collected until the participant discontinues the study or up to approximately 45 months
Secondary	Incidence of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs)	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.	From baseline up to Day 47 post last dose