Non-Small Cell Lung Cancer
Conditions
Keywords
Non-small Cell Lung Cancer, Trastuzumab Deruxtecan
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.
Interventions
DRUGTrastuzumab 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.
Sponsors
AstraZeneca
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 9 months after the last participant is randomized to data cut off, up to approximately 21 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer | 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months | 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. |
| Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer | 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months | 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. |
| Progression-free Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer | 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months | 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. |
| Overall Survival 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 | Overall survival (OS) is defined as the time from date of randomization until death from any cause. |
| 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 | — |
| 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 | 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months | 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. |
| 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) | — |
| 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) | — |
| Number of Participants With 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), up to Cycle 28 and End of Treatment. | — |
| 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 | At baseline and at end of treatment 40-day follow-up visit | 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. |
| Time to Deterioration in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) Scores | At baseline and at end of treatment 40-day follow-up visit | 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. |
| 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) | — |
Countries
Australia, Canada, France, Italy, Japan, Netherlands, South Korea, Spain, Taiwan, United States
Participant flow
Recruitment details
A total of 152 participants were enrolled and treated at clinic centers in North America, Europe, and Asia-Pacific.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg Participants randomized to receive trastuzumab deruxtecan 5.4 mg/kg, administered by intravenous infusion every 3 weeks (Q3W). | 102 |
| Trastuzumab Deruxtecan 6.4 mg/kg Participants randomized to receive trastuzumab deruxtecan 6.4 mg/kg, administered by intravenous infusion every 3 weeks (Q3W). | 50 |
| Total | 152 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 18 | 19 |
| Overall Study | Clinical Progression | 4 | 1 |
| Overall Study | Death | 4 | 2 |
| Overall Study | Other | 6 | 3 |
| Overall Study | Physician Decision | 4 | 0 |
| Overall Study | Progressive Disease | 61 | 23 |
| Overall Study | Randomized but not Treated | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Trastuzumab Deruxtecan 5.4 mg/kg | Trastuzumab Deruxtecan 6.4 mg/kg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 40 Participants | 15 Participants | 55 Participants |
| Age, Categorical Between 18 and 65 years | 62 Participants | 35 Participants | 97 Participants |
| Age, Continuous | 59.8 years STANDARD_DEVIATION 11.59 | 59.5 years STANDARD_DEVIATION 12.14 | 59.7 years STANDARD_DEVIATION 11.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 65 Participants | 31 Participants | 96 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 14 Participants | 12 Participants | 26 Participants |
| Race (NIH/OMB) White | 23 Participants | 5 Participants | 28 Participants |
| Sex: Female, Male Female | 65 Participants | 34 Participants | 99 Participants |
| Sex: Female, Male Male | 37 Participants | 16 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 52 / 102 | 24 / 50 |
| other Total, other adverse events | 101 / 101 | 50 / 50 |
| serious Total, serious adverse events | 42 / 101 | 26 / 50 |
Outcome results
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.
Time frame: 9 months after the last participant is randomized to data cut off, up to approximately 21 months
Population: Full Analysis Set includes all subjects for whom study treatment was assigned by randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | 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 | 50.0 percentage of participants |
| Trastuzumab Deruxtecan 6.4 mg/kg | 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 | 56.0 percentage of participants |
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.
Time frame: At baseline and at end of treatment 40-day follow-up visit
Population: Full Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | 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 | QLQ-LC13: Change from Baseline 40-Day Follow-up | -2.38 score on scale | Standard Deviation 24.335 |
| Trastuzumab Deruxtecan 5.4 mg/kg | 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 | QLQ-C30: Change from Baseline 40-Day Follow-up | -1.11 score on scale | Standard Deviation 17.78 |
| Trastuzumab Deruxtecan 6.4 mg/kg | 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 | QLQ-LC13: Change from Baseline 40-Day Follow-up | -29.17 score on scale | Standard Deviation 27.817 |
| Trastuzumab Deruxtecan 6.4 mg/kg | 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 | QLQ-C30: Change from Baseline 40-Day Follow-up | 15.63 score on scale | Standard Deviation 31.947 |
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.
Time frame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Population: Full Analysis Set includes all subjects for whom study treatment was assigned by randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer | 90.2 Percentage of participants |
| Trastuzumab Deruxtecan 6.4 mg/kg | Disease Control Rate Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer | 88.0 Percentage of participants |
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.
Time frame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Population: Full Analysis Set includes all subjects for whom study treatment was assigned by randomization. From the Full Analysis Set, 47 participants had a confirmed CR or PR in T-DXd 5.4 mg/kg arm, and 28 participants in T-DXd 6.4 mg/kg arm
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | Duration of Response Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer | 11.1 months |
| Trastuzumab Deruxtecan 6.4 mg/kg | Duration of Response Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer | 12.9 months |
Secondary
Number of Participants With Anti-Drug Antibodies (ADA) Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors
Time frame: Pre-dose on Day 1 of Cycles 1, 2 and 4, and then every 4 cycles (each cycle is 21 days), up to Cycle 28 and End of Treatment.
Population: The Immunogenicity Analysis Set included all subjects who received at least one dose of the study drug and who had at least one baseline or post-baseline immunogenicity assessment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors | 2 Participants |
| Trastuzumab Deruxtecan 6.4 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors | 1 Participants |
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.
Time frame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | Overall Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors | 19.0 months |
| Trastuzumab Deruxtecan 6.4 mg/kg | Overall Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer Tumors | 17.9 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.
Time frame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Population: Full Analysis Set includes all subjects for whom study treatment was assigned by randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | 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 | 46.1 Percentage of participants |
| Trastuzumab Deruxtecan 6.4 mg/kg | 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 | 56.0 Percentage of participants |
Secondary
Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
Time frame: 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)
Population: The PK Analysis Set included all randomized subjects who received at least one dose of study drug and had any measurable post-dose serum concentrations of T-DXd, total anti-HER2 antibody, and DXd.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Trastuzumab Deruxtecan | 658 µg × d/mL | Standard Deviation 185 |
| Trastuzumab Deruxtecan 5.4 mg/kg | Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Total Anti-HER2 Antibody | 697 µg × d/mL | Standard Deviation 208 |
| Trastuzumab Deruxtecan 5.4 mg/kg | Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | DXd (Metabolite Active Metabolite MAAA-1181a) | .050 µg × d/mL | Standard Deviation 0.022 |
| Trastuzumab Deruxtecan 6.4 mg/kg | Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Trastuzumab Deruxtecan | 793 µg × d/mL | Standard Deviation 210 |
| Trastuzumab Deruxtecan 6.4 mg/kg | Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Total Anti-HER2 Antibody | 829 µg × d/mL | Standard Deviation 261 |
| Trastuzumab Deruxtecan 6.4 mg/kg | Pharmacokinetic Parameter Area Under the Serum Concentration-Time Curve (AUC) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | DXd (Metabolite Active Metabolite MAAA-1181a) | .059 µg × d/mL | Standard Deviation 0.017 |
Secondary
Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
Time frame: 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)
Population: The PK Analysis Set included all randomized subjects who received at least one dose of study drug and had any measurable post-dose serum concentrations of T-DXd, total anti-HER2 antibody, and DXd.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Trastuzumab Deruxtecan | 148 µg/mL | Standard Deviation 69.5 |
| Trastuzumab Deruxtecan 5.4 mg/kg | Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Total Anti-HER2 Antibody | 138 µg/mL | Standard Deviation 57.8 |
| Trastuzumab Deruxtecan 5.4 mg/kg | Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | DXd (Metabolite Active Metabolite MAAA-1181a) | .015 µg/mL | Standard Deviation 0.007 |
| Trastuzumab Deruxtecan 6.4 mg/kg | Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Trastuzumab Deruxtecan | 196 µg/mL | Standard Deviation 184 |
| Trastuzumab Deruxtecan 6.4 mg/kg | Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Total Anti-HER2 Antibody | 179 µg/mL | Standard Deviation 194 |
| Trastuzumab Deruxtecan 6.4 mg/kg | Pharmacokinetic Parameter Maximum Serum Concentration (Cmax) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | DXd (Metabolite Active Metabolite MAAA-1181a) | .018 µg/mL | Standard Deviation 0.008 |
Secondary
Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a
Time frame: 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)
Population: The PK Analysis Set included all randomized subjects who received at least one dose of study drug and had any measurable post-dose serum concentrations of T-DXd, total anti-HER2 antibody, and DXd.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Trastuzumab Deruxtecan | 5.47 µg/mL | Standard Deviation 11.1 |
| Trastuzumab Deruxtecan 5.4 mg/kg | Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Total Anti-HER2 Antibody | 6.39 µg/mL | Standard Deviation 10.7 |
| Trastuzumab Deruxtecan 5.4 mg/kg | Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | DXd (Metabolite Active Metabolite MAAA-1181a) | .0003 µg/mL | Standard Deviation 0.0003 |
| Trastuzumab Deruxtecan 6.4 mg/kg | Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Trastuzumab Deruxtecan | 5.84 µg/mL | Standard Deviation 3.48 |
| Trastuzumab Deruxtecan 6.4 mg/kg | Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | Total Anti-HER2 Antibody | 7.16 µg/mL | Standard Deviation 5 |
| Trastuzumab Deruxtecan 6.4 mg/kg | Pharmacokinetic Parameter Minimum Observed Concentration (Ctrough) for Trastuzumab Deruxtecan, Total Anti-HER2 Antibody, and Active Metabolite MAAA-1181a | DXd (Metabolite Active Metabolite MAAA-1181a) | .0003 µg/mL | Standard Deviation 0.0002 |
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.
Time frame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Population: Full Analysis Set includes all subjects for whom study treatment was assigned by randomization
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | Progression-free Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer | 9.7 months |
| Trastuzumab Deruxtecan 6.4 mg/kg | Progression-free Survival Following Intravenous Administration of Trastuzumab Deruxtecan in Participants With Metastatic Non-small Cell Lung Cancer | 9.5 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
Time frame: 9 months after the last participant is randomized or later to data cut off, up to approximately 35 months
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | 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 | 101 Participants |
| Trastuzumab Deruxtecan 6.4 mg/kg | 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 | 50 Participants |
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.
Time frame: At baseline and at end of treatment 40-day follow-up visit
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab Deruxtecan 5.4 mg/kg | Time to Deterioration in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) Scores | 8.6 months |
| Trastuzumab Deruxtecan 6.4 mg/kg | Time to Deterioration in European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) Scores | 9.3 months |