January 18, 2022
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January 31, 2022
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April 17, 2024
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March 4, 2022
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February 29, 2028 (Final data collection date for primary outcome measure)
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- Progression-free Survival Based on Blinded Independent Central Review in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 32 months ]
Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1.
- Overall Survival in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab [ Time Frame: From randomization until date of death due to any cause, up to approximately 53 months ]
Overall Survival (OS) is defined as the time from randomization to death due to any cause.
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Same as current
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- Objective Response Rate by Blinded Independent Central Review in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 32 months ]
Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by BICR per RECIST Version 1.1.
- Progression-free Survival by Investigator in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 32 months ]
Progression-free Survival (PFS) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by the Investigator per RECIST Version 1.1.
- Progression-free Survival 2 in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 53 months ]
Progression-free Survival 2 (PFS2) is defined as the time from randomization to the first documented radiographic disease progression or death due to any cause, whichever occurs first, assessed by local standard clinical practice.
- Objective Response Rate by Investigator in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 32 months ]
Objective Response Rate (ORR) is defined as the proportion of participants who achieved a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), assessed by the Investigator per RECIST Version 1.1.
- Duration of Response by BICR and Investigator in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab [ Time Frame: From date of first objective response (CR or PR) to date of first radiographic disease progression or death due to any cause (whichever occurs first), up to approximately 32 months ]
Duration of Response (DoR) is defined as the time from the date of the first documentation of objective response (confirmed CR or confirmed PR) to the date of the first radiographic disease progression or death due to any cause, whichever occurs first, assessed by BICR and by the Investigator per RECIST Version 1.1.
- Time to Response by BICR and Investigator in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab [ Time Frame: From randomization to date of first objective response (CR or PR), up to approximately 32 months ]
Time to Response (TTR) is defined as the time from randomization to the date of the first documentation of objective response (confirmed CR or confirmed PR) in responding participants, assessed by BICR and by the Investigator per RECIST Version 1.1.
- Disease Control Rate by BICR and Investigator in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 32 months ]
Disease Control Rate (DCR) is defined as the proportion of participants who achieved a BOR of confirmed CR, confirmed PR, or stable disease (SD), assessed by BICR and by the Investigator per RECIST Version 1.1.
- Time to Deterioration in Participants Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 53 months ]
Time to Deterioration (TTD) is defined as the time from randomization to first onset of a ≥10-point increase in cough, chest pain, or dyspnea, confirmed by a second adjacent ≥10-point increase from randomization in the same symptom, or confirmed by death within 21 days of a ≥10-point increase from randomization, assessed the European Organization for Research and Treatment of Cancer Lung cancer module (EORTC-QLQ-LC13).
- Number of Participants With Treatment-emergent Adverse Events (TEAE) Who Were Administered Dato-DXd in Combination With Pembrolizumab Compared With Pembrolizumab [ Time Frame: Up to 53 months ]
A TEAE is defined as an AE with a start or worsening date on or after the start date of study treatment until 37 days after the end date of study treatment.
- Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline) and Proportion of Participants Who Have Treatment-emergent ADA [ Time Frame: Baseline and up to 53 months ]
The immunogenicity of Dato-DXd in combination with pembrolizumab will be assessed.
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Same as current
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Not Provided
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Not Provided
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Study of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in the First-line Treatment of Subjects With Advanced or Metastatic NSCLC Without Actionable Genomic Alterations
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A Randomized, Open-label, Phase 3 Trial of Dato-DXd Plus Pembrolizumab vs Pembrolizumab Alone in Treatment-naïve Subjects With Advanced or Metastatic PD-L1 High (TPS ≥50%) Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung08)
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This study is designed to assess the efficacy and safety of datopotamab deruxtecan (Dato-DXd) in combination with pembrolizumab versus pembrolizumab alone in participants with advanced or metastatic non-small cell lung cancer (NSCLC).
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The primary objective of the study is to compare the efficacy of Dato-DXd and pembrolizumab with pembrolizumab alone in terms of either Progression Free Survival (PFS) or Overall Survival (OS) for participants with advanced or metastatic NSCLC without actionable genomic alterations whose tumor has high programmed death-ligand 1 (PD-L1) expression (tumor proportion score; TPS ≥50%) and who have not previously received systemic therapy for advanced or metastatic NSCLC.
Eligible participants will be randomized in a 1:1 ratio to the control arm (pembrolizumab alone) or the experimental arm (Dato-DXd and pembrolizumab). The study will be divided into 4 periods: Tissue Screening Period, Screening Period, Treatment Period, and Follow-up Period.
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Interventional
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Phase 3
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Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment
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Metastatic Non Small Cell Lung Cancer
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- Drug: Datopotamab Deruxtecan
Dato-DXd will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
Other Name: Dato-DXd
- Drug: Pembrolizumab
Pembrolizumab will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle.
Other Name: KEYTRUDA®
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- Experimental: Pembrolizumab + Datopotamab Deruxtecan (Dato-DXd)
Participants will be randomized to receive 200 mg pembrolizumab followed by 6.0mg/kg Dato-DXd.
Interventions:
- Drug: Datopotamab Deruxtecan
- Drug: Pembrolizumab
- Active Comparator: Pembrolizumb
Participants will be randomized to receive 200 mg pembrolizumab.
Intervention: Drug: Pembrolizumab
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Not Provided
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Recruiting
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740
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Same as current
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April 30, 2028
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February 29, 2028 (Final data collection date for primary outcome measure)
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Inclusion Criteria:
Participants eligible for inclusion in the study must meet all inclusion criteria within 28 days of randomization into the study.
Exclusion Criteria:
- Has received prior systemic treatment for advanced or metastatic NSCLC.
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Has received prior treatment for NSCLC with any of the following, including in the adjuvant/neoadjuvant setting:
- Any agent, including an antibody-drug conjugate, containing a chemotherapeutic agent targeting topoisomerase I.
- TROP2-targeted therapy.
- Any anti-programmed death receptor-1 (PD-1), anti-PD-L1, or anti-PD-ligand 2 (L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137).
- Any other immune checkpoint inhibitors. Participants who received adjuvant or neoadjuvant therapy OTHER than those listed above, are eligible if the adjuvant/neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced/metastatic disease.
- Has spinal cord compression or active and untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable.
- Has received prior radiotherapy ≤4 weeks of start of study intervention or more than 30 Gy (unit of ionizing radiation dose in the International System of Units) to the lung within 6 months of Cycle 1 Day 1.
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History of another primary malignancy (beyond NSCLC) except for:
- Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study treatment and of low potential risk for recurrence.
- Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- Adequately treated carcinoma in situ without evidence of disease.
- Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage ≤T2cN0M0 without biochemical recurrence or progression and who in the opinion of the Investigator are not deemed to require active intervention.
- Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis including radiation pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
- Clinically severe pulmonary compromise, as judged by the investigator, resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement or prior complete pneumonectomy.
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Uncontrolled or significant cardiovascular disease, including:
- Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval >470 msec regardless of sex (based on the average of the 12-lead electrocardiogram determination at screening).
- Myocardial infarction within 6 months prior to randomization.
- Uncontrolled angina pectoris within 6 months prior to randomization.
- LVEF <50% by ECHO or MUGA scan within 28 days before randomization.
- New York Heart Association Class 2 to 4 congestive heart failure (CHF) at screening.
- Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) within 28 days before randomization.
Participants with a history of Class 2 to 4 CHF prior to screening, must have returned to Class 1 CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days before randomization) in order to be eligible.
- Clinically significant corneal disease.
- Has received a live vaccine or live-attenuated vaccine (messenger ribonucleic acid and replication-incompetent adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of study drug. For any participant receiving an approved severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccine, please follow the vaccine label and/or local guidance.
- Active, known, or suspected autoimmune disease (has an active autoimmune disease that has required systemic treatment in the past 2 years).
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosage >10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy ≤7 days prior to the first dose of study drug.
- Has known human immunodeficiency virus (HIV) infection that is not well controlled.
- Has an active hepatitis or uncontrolled hepatitis B or active hepatitis C infection.
- Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
- Had an allogeneic tissue/solid organ transplant.
- Has a history of severe hypersensitivity reactions to either the drug or inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd or pembrolizumab.
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Sexes Eligible for Study: |
All |
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18 Years and older (Adult, Older Adult)
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No
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Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, France, Germany, Greece, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, Romania, Spain, Switzerland, Taiwan, Thailand, Turkey, United Kingdom, United States
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NCT05215340
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DS1062-A-U304 2021-002555-10 ( EudraCT Number ) KEYNOTE-C73 ( Other Identifier: Merck ) MK3475-C73 ( Other Identifier: Merck )
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Yes
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Studies a U.S. FDA-regulated Drug Product: |
Yes |
Studies a U.S. FDA-regulated Device Product: |
No |
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Plan to Share IPD: |
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 Materials: |
Study Protocol |
Supporting Materials: |
Statistical Analysis Plan (SAP) |
Supporting Materials: |
Informed Consent Form (ICF) |
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/ |
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Daiichi Sankyo
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Same as current
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Daiichi Sankyo
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Same as current
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- AstraZeneca
- Merck Sharp & Dohme LLC
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Study Director: |
Global Clinical Leader |
Daiichi Sankyo |
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Daiichi Sankyo
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April 2024
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