Trastuzumab Deruxtecan in Participants With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC)

Non-Small Cell Lung Cancer Clinical Trial

— DESTINY-LUNG02  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04644237
• Other study ID #: DS8201-A-U206
• Secondary ID: 2020-003427-42
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 19, 2021
• Est. completion date: August 31, 2024

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 152
• Est. completion date: August 31, 2024
• Est. primary completion date: December 23, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Trastuzumab deruxtecan
Trastuzumab deruxtecan 100 mg will be provided as a sterile lyophilized powder and reconstituted with 5 mL water for injection (final concentration 20 mg/mL [ie, 100 mg/5 mL]). The study drug will be administered as an intravenous (IV) infusion over 30 to 90 min Q3W ± 2 days. The initial dose of study drug will be infused for 90 ± 10 min.

Locations

Country	Name	City	State
Australia	St John of God Subiaco Hospital	Subiaco
Australia	Princess Alexandra Hospital	Woolloongabba
Canada	University Health Network	Toronto
France	Centre Leon Berard	Lyon
France	Assistance Publique Hopitaux de Marseille AP-HM, Hopital NORD	Marseille
France	Hopital Pontchaillou	Rennes
France	CHU Nantes	Saint-Herblain
France	CHU toulouse - hôpital Larrey	Toulouse
France	Gustav Roussy	Villejuif
Italy	Ospedale San Luca	Lucca
Italy	IRCCS Istituto Europeo di Oncologia	Milano
Italy	SC Oncologia, AOU Policlinico Modena	Modena
Italy	Istituto Nazionale Tumori Fondazione G. Pascale di Napoli Strutturadi Oncologia	Napoli
Italy	Azienda Ospedaliero-Universitaria San Luigi Gonzaga	Orbassano
Italy	Humanitas Cancer Center Istituto Clinico Humanitas	Rozzano
Japan	Aichi Cancer Center Hospital	Chikusa
Japan	National Cancer Central Hospital	Chuo Ku
Japan	National Hospital Organization Kyushu Cancer Center	Fukuoka
Japan	National Cancer Center Hospital East	Kashiwa
Japan	Okayama University Hospital	Okayama
Japan	Kindai University Hospital	Osaka-sayama
Korea, Republic of	Chungbuk National University Hospital	Chungbuk
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	Netherlands Cancer Institute	Amsterdam
Netherlands	Erasmus MC	Rotterdam
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Clinica Universidad de Navarra	Madrid
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital Universitario Fundacion Jimenez Diaz	Madrid
Spain	Hospital Universitari i Politècnic La Fe	Valencia
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital NCKUH	Tainan
Taiwan	National Taiwan University Hospital	Taipei City
Taiwan	Chang Gung Memorial Hospital CGMH - LinKou Branch	Taoyuan
United States	University of Colorado Denver - Anschutz Medical Campus	Aurora	Colorado
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Henry Ford Cancer Institute/Henry Ford Hospital	Detroit	Michigan
United States	University of Michigan	Detroit	Michigan
United States	Virgina Cancer Specialists	Fairfax	Virginia
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	AdventHealth Orlando	Orlando	Florida
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo	AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Canada,  France,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Confirmed objective response rate (ORR), defined as the proportion of participants with complete response (CR) or partial response (PR), was assessed by blinded independent central review (BICR) based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. 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.	9 months after the last participant is randomized to data cut off, up to approximately 21 months
Secondary	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	Confirmed objective response rate (ORR), defined as the percentage of participants with complete response (CR) or partial response (PR), will be assessed by the Investigator based on Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1. 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.	9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary	Duration of Response Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer	Duration of response (DoR) is defined as the time from the initial response (complete response [CR] or partial response [PR]) until documented tumor progression or death from any cause. DoR is only defined for participants who achieved confirmed CR or PR. 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.	9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary	Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer	Disease control rate (DCR) is the sum of complete response (CR), partial response (PR), and stable disease (SD) rates. 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.	9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary	Progression-free Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer	Progression-free survival (PFS) is defined as the time from date of randomization until first objective radiographic tumor progression or death from any cause, based on blinded independent central review (BICR) and investigator assessment.	9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary	Overall Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors	Overall survival (OS) is defined as the time from date of randomization until death from any cause.	9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary	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		9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Secondary	Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a		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)
Secondary	Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a		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)
Secondary	Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a		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)
Secondary	Incidence of Anti-Drug Antibodies (ADA) Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors		Pre-dose on Day 1 of Cycles 1, 2 and 4, and then every 4 cycles (each cycle is 21 days)
Secondary	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	The EORTC QLQ-C30 consists of 30 questions assessing global health-related quality of life, five aspects of subject functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), and six single-items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales and single-item measures range in score from 0 to 100. Higher scores for functioning scales and global health status indicate a better level of functioning while higher scores on the symptom and single-item scales indicate a higher level of symptoms. The QLQ-LC13 is a 13-item questionnaire designed to assess lung cancer-related symptoms and treatment side effects. The scales ranges from 1=not at all to 4=very much. The summation of scores range from 0 to 100, where higher scores represent increasing symptoms levels.; scales.	On Day 1 of every cycle (each cycle is 21 days), and at end of treatment visit 40-day follow-up visit
Secondary	Time to Deterioration in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) Scores	The EORTC QLQ-C30 consists of 30 questions assessing global health-related quality of life, five aspects of subject functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, and pain), and six single-items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). All of the scales and single-item measures range in score from 0 to 100. Higher scores for functioning scales and global health status indicate a better level of functioning while higher scores on the symptom and single-item scales indicate a higher level of symptoms.	On Day 1 of every cycle (each cycle is 21 days), and at end of treatment visit 40-day follow-up visit