Japanease

Nov. 06, 2020

Feb. 19, 2021

jRCT2031200186

A Phase 2 Randomized Open-Label Study of Patritumab Deruxtecan (U3-1402) in Subjects With Previously Treated Metastatic or Locally Advanced EGFRmutated Non-Small Cell Lung Cancer (NSCLC) - HERTHENA-Lung01
(HERTHENA-Lung01)

Patritumab Deruxtecan in Subjects with Metastatic or Locally Advanced EGFR-mutated NSCLC

Nagao Kiminori

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Contact for Clinical Trial Information

DAIICHI SANKYO Co.,Ltd.

1-2-58, Hiromachi, Shinagawa-ku, Tokyo

+81-3-6225-1111

dsclinicaltrial@daiichisankyo.co.jp

Nov. 09, 2020

420

Interventional

randomized controlled trial

open(masking not used)

uncontrolled control

parallel assignment

treatment purpose

Australia/France/Italy/Singapore/Singapore/South Korea/Spain/Taiwan/United States/Germany

Sign and date the tissue 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:
>= 1 prior line(s) of EGFR TKI treatment (erlotinib, gefitinib, afatinib, dacomitinib or osimertinib). Particiants receiving an EGFR TKI at the time of signing informed should continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1. EGFR T790M mutation-positive participants (previously treated with erlotinib, gefitinib, afatinib or dacomitinib) must have received and have documentation of radiological disease progression following treatment with osimertinib.
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 status (ECOG PS) of 0 or 1 at Screening.
Has adequate bone marrow reserve and organ function as defined by the protocol within 14 days prior to Cycle 1 Day 1.
Platelet count : >=100,000/mm^3 or >=100 x 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 x 10^9/L
Serum creatinine (SCr) or creatinine clearance (CrCl): SCr <=1.5 x 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 x ULN (if liver metastases are present, <=5 x ULN)
Total bilirubin: <=1.5 x ULN if no liver metastases (<3 x 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 x 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

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 of 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.

20age old over
No limit

Both

Metastatic or Locally Advanced Non-Small Cell Lung Cancer

Arm 1: patritumab deruxtecan will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.
Arm 2: patritumab deruxtecan will be at up-titration dose 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 on Day 1 of each 21-day cycle.

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.
[Time Frame: 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 26 months]

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.
[Time Frame: 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 26 months]
Progression-free Survival (PFS)
PFS is defined as the time from the start of study treatment to the earlier of the dates of the first documentation of objective PD per RECIST v1.1 or death due to any cause. PFS will be determined by BICR and by Investigator, respectively.
[Time Frame: Data collected from screening until time of disease progression by BICR, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to 26 months]
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.
[Time Frame: Data collected from screening until time of disease progression, death, lost to follow up, study discontinuation, whichever occurs first, assessed up to approximately 26 months]
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.
[Time Frame: 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 26 months]
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.
[Time Frame: 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 26 months]
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
[Time Frame: 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 26 months]
Overall Survival (OS)
OS defined as the time from the start of study treatment to the date of death due to any cause.
[Time Frame: Death date is collected until the participant discontinues the study or up to approximately 26 months
Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interests (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.
[Time Frame: From baseline up to Day 47 post last dose]

Recruiting

DAIICHI SANKYO Co.,Ltd.
National Cancer Ctr IRB#2-j
5-1-1, Tsukiji, Chuo-ku, Tokyo

+81-3-3542-2511

Chiken_CT@ml.res.ncc.go.jp
Approval

Nov. 04, 2020

Yes

Plan Description: 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/ Supporting Documents: - Study Protocol - Statistical Analysis Plan - Clinical Study Report 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. URL: https://vivli.org/ourmember/daiichi-sankyo/