Trastuzumab deruxtecan for subjects with HER2-mutated metastatic NSCLC

JRCT ID: jRCT2061200038

Registered date:24/12/2020

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Non-Small Cell Lung Cancer
• Date of first enrollment: 02/03/2021
• Target sample size: 150
• Countries of recruitment: Australia,Japan,Canada,Japan,France,Japan,Italy,Japan,Netherlands,Japan,South Korea,Japan,Spain,Japan,Taiwan,Japan,US,Japan
• Study type: Interventional
• Intervention(s): Trastuzumab deruxtecan will be administered at either 5.4 or 6.4 mg/kg by intravenous infusion every 3 weeks.

Outcome(s)

• Primary Outcome: Objective Response Rate by Blinded Independent Central Review Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors

Secondary Outcome

- Objective Response Rate by Investigator Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors
- Duration of Response Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
- Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
- Progression-free Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer
- Overall Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Nonsmall Cell Lung Cancer Tumors
- 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
- Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
- Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti- HER2 Antibody, and Active Metabolite MAAA-1181a
- Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
- Incidence of Anti-Drug Antibodies (ADA) Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors
- 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
- Time to deterioration in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life
- Questionnaire (QLQ-C30) scores

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include 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 (second line or later [2L+], including platinum therapy), not amenable to curative surgery or radiation
- 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. Fine needle aspirates are not acceptable.
- Eastern Cooperative Oncology Group performance status 0 to 1
- Left ventricular ejection fraction >= 50% within 28 days before randomization
- 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

Exclude criteria

- Known driver mutation in the epidermal growth factor receptor (EGFR) or BRAF gene or a known anaplastic lymphoma kinase (ALK) or ROS1 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 enrollment 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), based on available blood tests, liver ultrasound, or liver biopsy results
- 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

Related Information

• Primary Sponsor: Inoguchi Akihiro
• Secondary Sponsor: AstraZeneca
• Secondary ID(s): NCT04644237