Clinical trial NCT04644237: Trastuzumab Deruxtecan in Participants With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC)
Official title: A Phase 2, Multicenter, Randomized Study of Trastuzumab Deruxtecan in Subjects With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC) (DESTINY-LUNG02)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: Non-small Cell Lung Cancer
Trastuzumab Deruxtecan
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
Collaborators: name: AstraZeneca
First posted: 2020-11-25
Enrollment: 152
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 was designed to evaluate the safety and efficacy of trastuzumab deruxtecan in HER2-mutated metastatic non-small cell lung cancer (NSCLC) participants who had disease recurrence or progression during/after at least one regimen of prior anticancer therapy (second line or later) that must have contained a platinum-based chemotherapy drug.

Detailed description: This randomized, two-arm, phase 2, multicenter study will evaluate the safety and efficacy of 5.4 mg/kg and 6.4 mg/kg trastuzumab deruxtecan administered every 3 weeks (Q3W) in participants with HER2-mutated metastatic NSCLC. Each participant is expected to receive approximately 14 months of trastuzumab deruxtecan treatment. The primary endpoint of the study will be confirmed objective response rate (blinded independent central review). Secondary endpoints will include, but not limited to, disease control rate, duration of response, progression-free survival, objective response rate (investigator), overall survival, and safety.

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Men or women ≥18 years, follow local regulatory requirements if the legal age of the consent for study participation is \>18 years
* Pathologically documented metastatic NSCLC with a known activating HER2 mutation. Note: A HER2 mutation documented only from a liquid biopsy samples cannot be used for enrollment.
* Had previous treatment including platinum therapy in the metastatic/locally advanced setting and not amenable to curative surgery or radiation. Participant must have progressed during or after the last treatment regimen or discontinued because of unacceptable toxicity.
* Presence of at least 1 measurable lesion confirmed by the blinded Independent Central Review based on RECIST version 1.1
* Willing and able to provide an archival tumor tissue sample. A fresh biopsy is required if an archival tumor tissue sample cannot be supplied. Resection and core needle biopsy are acceptable. Fine needle aspirates or cell block are not acceptable.
* Eastern Cooperative Oncology Group performance status 0 to 1
* Left ventricular ejection fraction ≥ 50% within 28 days before randomization Resection and core needle biopsy are acceptable - Adequate organ function as specified in protocol within 14 days before randomization
* Adequate treatment washout period before randomization
* Participants of reproductive/childbearing potential agree to use a highly effective form of contraception (or avoid intercourse) during study period and up to 7 months (females) and 4 months (males) after last study dose
* Males should not freeze or donate sperm throughout the study period up to at least 4 months after last study dose; females should not donate or retrieve ova for their own use throughout the study period and up to at least 7 months after last study dose
* Life expectancy 3 months or more

Exclusion Criteria:

* Known driver mutation in the epidermal growth factor receptor (EGFR), BRAF, or MET exon 14 gene or a known anaplastic lymphoma kinase (ALK), ROS1, RET, or NTRK fusion
* Medical history of myocardial infarction within 6 months before randomization, symptomatic congestive heart failure (CHF) (New York Heart Association Class II to IV). Participants with troponin levels above upper limit of normal at screening (as defined by the manufacturer) and without any myocardial infarction (MI)-related symptoms should have a cardiologic consultation before randomization to rule out MI
* Corrected QT interval (QTcF) prolongation \> 470 msec (females) or \>450 msec (males) based on average of the triplicate12-lead electrocardiogram at screening
* History of non-infectious interstitial lung disease (ILD)/pneumonitis that required steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening
* Spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms
* Multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated
* History of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product
* History of severe hypersensitivity reactions to other monoclonal antibodies
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
* Substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the participant's participation in the clinical study or evaluation of the clinical study results
* Known human immunodeficiency virus (HIV) infection
* Known active, clinically relevant liver disease (eg, active hepatitis B, or active hepatitis C) such as those with serologic evidence of viral infection within 28 days of Cycle 1, Day 1
* Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline
* Pregnant, breastfeeding, or planning to become pregnant
* Otherwise considered inappropriate for the study by the Investigator
* Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (eg. pulmonary emboli within three months of the study randomization, severe asthma, severe COPD, restrictive lung disease, pleural effusion, etc.)
* Any autoimmune, connective tissue or inflammatory disorders (e.g., Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening
* Prior complete pneumonectomy
* Had prior treatment with any agent, including an antibody drug conjugate (ADC), containing a chemotherapeutic agent targeting topoisomerase I

Primary outcomes:
measure: Percentage of Participants With Confirmed Objective Response Rate by Blinded Independent Central Review Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
timeFrame: 9 months after the last participant is randomized to data cut off, up to approximately 21 months
Secondary outcomes:
measure: Percentage of Participants With Confirmed Objective Response Rate by Investigator Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung CancerTumors
timeFrame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
measure: Duration of Response Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
timeFrame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
measure: Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
timeFrame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
measure: Progression-free Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
timeFrame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
measure: Overall Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors
timeFrame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
measure: The Percentage of Participants Reporting Treatment-emergent Adverse Events Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors
timeFrame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
measure: Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
timeFrame: Cycle 1 Day 1; Cycle 2 Day 1, and Cycle 3 Day 1: pre- and post-dose; Cycle 1 Day 8: 7 days post-dose; Cycle 1 Day 15: 14 days post-dose; Cycle 4 Day 1 and Cycle 6 Day 1: pre-dose (each cycle is 21 days)
measure: Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
timeFrame: Cycle 1 Day 1; Cycle 2 Day 1, and Cycle 3 Day 1: pre- and post-dose; Cycle 1 Day 8: 7 days post-dose; Cycle 1 Day 15: 14 days post-dose; Cycle 4 Day 1 and Cycle 6 Day 1: pre-dose (each cycle is 21 days)
measure: Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
timeFrame: Cycle 1 Day 1; Cycle 2 Day 1, and Cycle 3 Day 1: pre- and post-dose; Cycle 1 Day 8: 7 days post-dose; Cycle 1 Day 15: 14 days post-dose; Cycle 4 Day 1 and Cycle 6 Day 1: pre-dose (each cycle is 21 days)
measure: Incidence of Anti-Drug Antibodies (ADA) Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors
timeFrame: Pre-dose on Day 1 of Cycles 1, 2 and 4, and then every 4 cycles (each cycle is 21 days)
measure: Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and EORTC Quality of Life Questionnaire for Lung Cancer Trials (QLQ-LC13) Scores
timeFrame: On Day 1 of every cycle (each cycle is 21 days), and at end of treatment visit 40-day follow-up visit
measure: Time to Deterioration in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) Scores
timeFrame: On Day 1 of every cycle (each cycle is 21 days), and at end of treatment visit 40-day follow-up visit
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver - Anschutz Medical Campus
state: Colorado
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital (MGH) - Hematology/Oncology
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: Detroit
country: United States
facility: University of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Fairfax
country: United States
facility: Virgina Cancer Specialists
state: Virginia
city: Subiaco
country: Australia
facility: St John of God Subiaco Hospital
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
city: Toronto
country: Canada
facility: University Health Network
city: Lyon
country: France
facility: Centre Leon Berard
city: Marseille
country: France
facility: Assistance Publique Hopitaux de Marseille AP-HM, Hopital NORD
city: Rennes
country: France
facility: Hopital Pontchaillou
city: Saint-Herblain
country: France
facility: CHU Nantes
city: Toulouse
country: France
facility: CHU toulouse - hÃ´pital Larrey
city: Villejuif
country: France
facility: Gustav Roussy
city: Lucca
country: Italy
facility: Ospedale San Luca
city: Milano
country: Italy
facility: IRCCS Istituto Europeo di Oncologia
city: Modena
country: Italy
facility: SC Oncologia, AOU Policlinico Modena
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale di Napoli Strutturadi Oncologia
city: Orbassano
country: Italy
facility: Azienda Ospedaliero-Universitaria San Luigi Gonzaga
city: Rozzano
country: Italy
facility: Humanitas Cancer Center Istituto Clinico Humanitas
city: Chikusa
country: Japan
facility: Aichi Cancer Center Hospital
city: Chuo Ku
country: Japan
facility: National Cancer Central Hospital
city: Fukuoka
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Ōsaka-sayama
country: Japan
facility: Kindai University Hospital
city: Chungbuk
country: Korea, Republic of
facility: Chungbuk National University Hospital
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: Amsterdam
country: Netherlands
facility: Netherlands Cancer Institute
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra - P
city: Valencia
country: Spain
facility: Hospital Universitari i PolitÃ¨cnic La Fe
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital NCKUH
city: Taipei City
country: Taiwan
facility: National Taiwan University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital CGMH - LinKou Branch
Study officials:
affiliation: Daiichi Sankyo
name: Global Clinical Leader
role: STUDY_DIRECTOR
References: