Clinical Trials List
Protocol NumberDS1062-A-U303
NCT Number(ClinicalTrials.gov Identfier)NCT05555732
2022-11-30 - 2027-10-31
Phase III
Recruiting9
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
ICD-10C34.91
Malignant neoplasm of unspecified part of right bronchus or lung
ICD-10C34.92
Malignant neoplasm of unspecified part of left bronchus or lung
ICD-10C7A.090
Malignant carcinoid tumor of the bronchus and lung
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9162.9
Malignant neoplasm of bronchus and lung, unspecified
A Randomized Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in Subjects With No Prior Therapy for Advanced or Metastatic PD-L1 TPS
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Trial Applicant
Daiichi Sankyo Taiwan Ltd.
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 徐偉勛 無
- 陳冠宇 無
- 楊景堯 無
- Jih-Hsiang Lee 無
- 林宗哲 無
- Chong-Jen Yu 無
- 廖唯昱 無
- 蔡子修 無
- Chia-Chi Lin 無
- WEI-LI MA 無
- CHAO-CHI HO CHAO-CHI HO 無
- 吳尚俊 無
- YEN-TING LIN 無
- 廖斌志 無
- JIN-YUAN SHIH 無
- 許嘉林 無
- 林昭文 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 陳鴻仁 無
- Chia-Hsiang Li 無
- Yu-Chao Lin 無
- Chih-Yen Tu 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Heng-Sheng Chao 未分科
- Chi-Lu Chiang 無
- Chia-I Shen 無
- Yuh-Min Chen 無
- 郭懿萱 無
- Hsu-ching Huang 無
- YEN-HAN TSENG 無
- 張毓帆 無
- 蕭慈慧 無
- 趙恒勝 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Chien-Ying Liu 無
- Chih-Hung Chen 無
- Cheng-Ta Yang 無
- Chih-Liang Wang 無
- Ping-Chih Hsu 無
- 邱立忠 無
- 吳教恩 無
- 林定佑 無
- 黃宗禎 無
- Shih-Hong Li 無
- Wen-Cheng Chang 無
- Chih-Hsi Kuo 無
- 枋岳甫 無
- Fu-Tsai Chung 無
- 張境夫 無
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Metastatic Non Small Cell Lung Cancer
Objectives
Main Purpose:
1. Compare the efficacy of Dato-DXd plus pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus pemetrexed with platinum-based chemotherapy, as measured by progression-free survival (PFS) assessed by blinded independent central review (BICR)
2. Compare the efficacy of Dato-DXd plus pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus pemetrexed with platinum-based chemotherapy, measured as overall survival (OS)
Key secondary objectives:
1. Dato-DXd plus pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus pemetrexed and platinum-based chemotherapy, measured as objective response rate (ORR)
Other secondary purposes:
1. To further evaluate the efficacy of Dato-DXd plus pembrolizumab with or without platinum-containing chemotherapy versus pembrolizumab plus platinum-pemetrexed chemotherapy.
2. To evaluate patient-reported outcomes (PROs) of Dato-DXd plus pembrolizumab with or without platinum-based chemotherapy versus pembrolizumab plus platinum-pemetrexed chemotherapy
3. Further evaluate the safety of Dato-DXd plus pembrolizumab with or without platinum-containing chemotherapy versus pembrolizumab plus platinum-pemetrexed chemotherapy.
4. Evaluate the immunogenicity of Dato-DXd combined with pembrolizumab with or without platinum-containing chemotherapy
Exploratory purpose:
1. Describe the pharmacokinetics (PK) and evaluate the exposure-response relationship of Dato-DXd as an efficacy and safety test indicator
2. Evaluate biomarkers that may be associated with clinical benefit of Dato-DXd combined with pembrolizumab with or without platinum-based chemotherapy
3. Evaluate biomarkers that may be associated with adverse effects of Dato-DXd combined with pembrolizumab with or without platinum-based chemotherapy
4. Explore how changes in biomarkers may be associated with drug exposure, AEs, and clinical outcomes
5. PRO indicators to evaluate Dato-DXd combined with pembrolizumab with or without platinum-containing chemotherapy
Test Drug
Datopotamab deruxtecan (Dato-DXd；DS-1062a)
Active Ingredient
Datopotamab deruxtecan (Dato-DXd；DS-1062a)
Dosage Form
Lyophilized Powder for Injection
Dosage
100mg
Endpoints
Interim analysis of OS
No interim analysis (IA) was planned for PFS.
This trial is expected to conduct up to two OS IAs. The Lan–DeMets alpha-spending function with the O’Brien–Fleming stopping boundary was used to calculate the optimal efficacy margin based on the actual number of deaths observed to maintain an overall type I error rate of two-tailed α = 0.03999 (0.04999 if the null hypothesis of PFS was rejected and α was flipped to OS according to the hierarchical testing framework).
The primary efficacy analysis of PFS and OS will be performed using the log-rank test, stratified by the random assignment stratification factor, to compare the treatment group (Group A or B) with the control group (Group C).
Progression-free survival and OS will be summarized and presented graphically by treatment group using the Kaplan-Meier method, and medians and corresponding confidence intervals (CIs) for the medians will be calculated using the Brookmeyer and Crowley method. In addition, the event-free probability at different time points (eg, 3, 6, 9, and 12 months) will be estimated with corresponding CIs using the Greenwood formula that can calculate variance.
The Cox regression model will be used to stratify according to the random assignment stratification factor to estimate the HR between the treatment group (group A or group B) and the control group (group C), as well as the corresponding CI for PFS and OS.
The efficacy between group A and group B was not formally compared. The comparative efficacy of the two groups will be evaluated narratively, by providing BICR to assess the HR estimates of PFS and OS and the corresponding CIs.
No interim analysis (IA) was planned for PFS.
This trial is expected to conduct up to two OS IAs. The Lan–DeMets alpha-spending function with the O’Brien–Fleming stopping boundary was used to calculate the optimal efficacy margin based on the actual number of deaths observed to maintain an overall type I error rate of two-tailed α = 0.03999 (0.04999 if the null hypothesis of PFS was rejected and α was flipped to OS according to the hierarchical testing framework).
The primary efficacy analysis of PFS and OS will be performed using the log-rank test, stratified by the random assignment stratification factor, to compare the treatment group (Group A or B) with the control group (Group C).
Progression-free survival and OS will be summarized and presented graphically by treatment group using the Kaplan-Meier method, and medians and corresponding confidence intervals (CIs) for the medians will be calculated using the Brookmeyer and Crowley method. In addition, the event-free probability at different time points (eg, 3, 6, 9, and 12 months) will be estimated with corresponding CIs using the Greenwood formula that can calculate variance.
The Cox regression model will be used to stratify according to the random assignment stratification factor to estimate the HR between the treatment group (group A or group B) and the control group (group C), as well as the corresponding CI for PFS and OS.
The efficacy between group A and group B was not formally compared. The comparative efficacy of the two groups will be evaluated narratively, by providing BICR to assess the HR estimates of PFS and OS and the corresponding CIs.
Inclution Criteria
Key Inclusion Criteria:
Sign and date the Main ICF, prior to the start of any study- specific qualification procedures. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
Adults ≥18 at the time the Main ICF is signed. (Follow local regulatory requirements if the legal age of adult voluntary consent for study participation is >18 years old).
Has tumor with PD-L1 TPS <50% as determined by PD-L1 IHC 22C3 pharmDx assay by central testing (minimum of six slides). PD-L1 expression results available at the same central laboratory from screening for the purpose of entry into another Dato-DXd study may be used for tissue screening purposes in this study as long as the subject has not been randomized/enrolled in the other study.
Has provided a formalin-fixed tumor tissue sample (minimum of 4 × 4-micron sections or block equivalent) for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers. This tissue requirement is in addition to the tissue required for PD-L1 testing for tissue screening purposes. If a documented law or regulation prohibits (or does not approve) sample collection, then such sample will not be collected, and the subject is still eligible for the study.
Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC. Subjects who received adjuvant or neoadjuvant therapy other than those listed in the exclusion criteria are eligible if the adjuvant/ neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced/metastatic disease and should not have progressed on or within the 6 months of completion.
Has measurable disease based on local imaging assessment using RECIST v1.1; radiographic tumor assessment must be performed within 28 days before randomization.
Sign and date the Main ICF, prior to the start of any study- specific qualification procedures. Is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
Adults ≥18 at the time the Main ICF is signed. (Follow local regulatory requirements if the legal age of adult voluntary consent for study participation is >18 years old).
Has tumor with PD-L1 TPS <50% as determined by PD-L1 IHC 22C3 pharmDx assay by central testing (minimum of six slides). PD-L1 expression results available at the same central laboratory from screening for the purpose of entry into another Dato-DXd study may be used for tissue screening purposes in this study as long as the subject has not been randomized/enrolled in the other study.
Has provided a formalin-fixed tumor tissue sample (minimum of 4 × 4-micron sections or block equivalent) for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers. This tissue requirement is in addition to the tissue required for PD-L1 testing for tissue screening purposes. If a documented law or regulation prohibits (or does not approve) sample collection, then such sample will not be collected, and the subject is still eligible for the study.
Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC. Subjects who received adjuvant or neoadjuvant therapy other than those listed in the exclusion criteria are eligible if the adjuvant/ neoadjuvant therapy was completed at least 6 months prior to the diagnosis of advanced/metastatic disease and should not have progressed on or within the 6 months of completion.
Has measurable disease based on local imaging assessment using RECIST v1.1; radiographic tumor assessment must be performed within 28 days before randomization.
Exclusion Criteria
Key Exclusion Criteria:
Has received prior systemic treatment for advanced/metastatic NSCLC.
Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting (for NSCLC):
Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I
TROP2-targeted therapy
Any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137)
Any other ICIs Subjects 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 or metastatic disease.
Has received a live vaccine within 30 days prior to the first dose of study treatment.
Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. For any subject receiving an approved severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine, please follow the vaccine label and/or local guidance. The vaccine manufacturer and the date of administration should be recorded on the electronic case report form (Concomitant Medications page), as should any AEs relating to the vaccine (including hypersensitivity or allergies). Note: Any licensed SARS-CoV2 vaccine (including those authorized for emergency use) in a particular country is allowed in the study as long as the vaccine is an mRNA vaccine, replication-incompetent adenoviral vaccine, or inactivated vaccine. Such vaccines will be treated just as any other concomitant therapy.
Investigational vaccines (ie, those not licensed or authorized for emergency use) are not allowed.
Has spinal cord compression or clinically active untreated CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 2 weeks by repeat imaging (Note: Repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 7 days before the first dose of study drug. Note: A contrasted computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the brain at baseline (MRI with contrast preferred) is required for all subjects. For those subjects in whom CNS metastases are first discovered at the time of screening, the treating investigator must delay of study treatment to document stability of CNS metastases with repeat imaging at least 2 weeks later (in which case, repeat of all screening activity may be required).
Has uncontrolled or significant cardiovascular disease not controlled by maximal medical therapy, including:
Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval >470 msec regardless of sex (based on the 12-lead electrocardiogram [ECG] performed at screening).
Myocardial infarction within 6 months prior to Cycle 1 Day 1.
History of a serious cardiac arrhythmia requiring treatment
Uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.
Left ventricular ejection fraction (LVEF) <50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization.
New York Heart Association (NYHA) Class II-IV congestive heart failure (CHF) at screening. Subjects with a history of Class II to IV CHF prior to screening, must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days before randomization) in order to be eligible.
Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg within 28 days before randomization that is not resolved despite maximal medical therapy).
Clinically severe pulmonary compromise as judged by the investigator resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli diagnosed within 3 months of Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc) or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc), or prior complete pneumonectomy.
Has received prior systemic treatment for advanced/metastatic NSCLC.
Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant setting (for NSCLC):
Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I
TROP2-targeted therapy
Any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137)
Any other ICIs Subjects 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 or metastatic disease.
Has received a live vaccine within 30 days prior to the first dose of study treatment.
Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. For any subject receiving an approved severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccine, please follow the vaccine label and/or local guidance. The vaccine manufacturer and the date of administration should be recorded on the electronic case report form (Concomitant Medications page), as should any AEs relating to the vaccine (including hypersensitivity or allergies). Note: Any licensed SARS-CoV2 vaccine (including those authorized for emergency use) in a particular country is allowed in the study as long as the vaccine is an mRNA vaccine, replication-incompetent adenoviral vaccine, or inactivated vaccine. Such vaccines will be treated just as any other concomitant therapy.
Investigational vaccines (ie, those not licensed or authorized for emergency use) are not allowed.
Has spinal cord compression or clinically active untreated CNS metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 2 weeks by repeat imaging (Note: Repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for at least 7 days before the first dose of study drug. Note: A contrasted computed tomography (CT) scan or magnetic resonance imaging (MRI) scan of the brain at baseline (MRI with contrast preferred) is required for all subjects. For those subjects in whom CNS metastases are first discovered at the time of screening, the treating investigator must delay of study treatment to document stability of CNS metastases with repeat imaging at least 2 weeks later (in which case, repeat of all screening activity may be required).
Has uncontrolled or significant cardiovascular disease not controlled by maximal medical therapy, including:
Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) interval >470 msec regardless of sex (based on the 12-lead electrocardiogram [ECG] performed at screening).
Myocardial infarction within 6 months prior to Cycle 1 Day 1.
History of a serious cardiac arrhythmia requiring treatment
Uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.
Left ventricular ejection fraction (LVEF) <50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization.
New York Heart Association (NYHA) Class II-IV congestive heart failure (CHF) at screening. Subjects with a history of Class II to IV CHF prior to screening, must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days before randomization) in order to be eligible.
Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg within 28 days before randomization that is not resolved despite maximal medical therapy).
Clinically severe pulmonary compromise as judged by the investigator resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (eg, pulmonary emboli diagnosed within 3 months of Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc) or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc), or prior complete pneumonectomy.
The Estimated Number of Participants
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Taiwan
35 participants
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Global
1170 participants
