Clinical Trials List
Protocol NumberDS1062-A-U304
NCT Number(ClinicalTrials.gov Identfier)NCT05215340
2022-03-01 - 2028-04-30
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, 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)
-
Trial Applicant
Daiichi Sankyo Taiwan Ltd.
-
Sponsor
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Principal Investigator
Co-Principal Investigator
- Yung-Hung Luo 無
- Heng-Sheng Chao 未分科
- Chi-Lu Chiang 無
- 蕭慈慧 無
- Hsu-ching Huang 無
- 張毓帆 無
- Chao-Hua Chiu 無
- Chia-I Shen 無
- 趙恒勝 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
- 張晃智 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
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
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Metastatic Non Small Cell Lung Cancer
Objectives
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.
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
2. 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.
3. Progression-free Survival 2 in Participants Who Were Administered Dato-DXd in Combination With 5. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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).
9. 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.
10. 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.
Test Drug
datopotamab deruxtecan (Dato-DXd; INN: DS-1062a)
Active Ingredient
datopotamab deruxtecan
Dosage Form
Lyophilized Powder for Injection
Dosage
100mg
Endpoints
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 (TPS ≥50%) and who have not previously received systemic therapy for advanced or metastatic NSCLC.
Inclution Criteria
1. Sign and date the Tissue Screening and Main ICFs, prior to the start of any study-specific
qualification procedures.
2. Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time of informed
consent. (Follow local regulatory requirements if the legal age of adult voluntary consent for
study participation is >18 years old.)
3. Histologically documented NSCLC that meets all of the following criteria:
a. Stage IIIB or IIIC disease and not candidates for surgical resection or definitive
chemoradiation, or Stage IV NSCLC disease at the time of randomization (based on the
American Joint Committee on Cancer, Eighth Edition).
b. Documented negative test results for EGFR, ALK, and ROS1 actionable genomic
alterations based on analysis of tumor tissue. If test results for EGFR, ALK, and ROS1 are
not available, subjects are required to undergo testing performed locally for these genomic
alterations.
c. No known actionable genomic alterations in NTRK, BRAF, RET, MET, or other
actionable driver kinases with locally approved therapies. (Testing for genomic alterations
besides EGFR, ALK, and ROS1 is not required prior to enrollment.)
4. Has provided a formalin-fixed tumor tissue sample (minimum of 10 [preferably 15] × 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.
5. Tumor has high PD-L1 expression (TPS ≥50%) as determined by PD-L1 IHC 22C3 pharmDx
assay by central testing (minimum of 6 slides).
6. Has an adequate treatment washout period before Cycle 1 Day 1 defined as:
Treatment Washout Period
Major surgery ≥3 weeks
Radiation therapy including
palliative radiation to chest
≥4 weeks (a 2-week washout period is permitted
for palliative radiation to non-central nervous
system disease)
No more than 30Gys in lung fields in the past
6 months
7. Measurable disease based on local imaging assessment using RECIST Version 1.1.
8. Has left ventricular ejection fraction (LVEF) ≥50% by either an echocardiogram (ECHO) or
multigated acquisition scan (MUGA) within 28 days before randomization.
9. ECOG PS of 0 or 1 at screening.
10. Has a life expectancy of at least 3 months.
11. Adequate bone marrow function within 7 days before randomization defined as:
Parameter Laboratory Value
Bone Marrow Function
Platelet count ≥100,000/mm3
(platelet transfusion is not allowed
within 1 week prior to screening assessment)
Hemoglobin ≥9.0 g/dL (criteria must be met without packed
red blood cell/plasma transfusion within 2 weeks
prior to screening assessment. Subjects can be on
stable dose of erythropoietin [≥ approximately
3 months])
Absolute neutrophil count ≥1500/mm3
(granulocyte-colony stimulating
factor administration is not allowed within
1 week prior to screening assessment)
Blood Clotting Function
International normalized
ratio/prothrombin time and
activated partial thromboplastin
time or partial thromboplastin
time
≤1.5 × upper limit of normal (ULN) unless
subject is receiving anticoagulant therapy as long
as prothrombin time or activated partial
thromboplastin time is within therapeutic range of
intended use of anticoagulants
Renal Function
Creatinine clearance ≥30 mL/min, as calculated using the CockcroftGault equationa
Hepatic Function
Alanine
aminotransferase/aspartate
aminotransferase
≤2.5 × ULN (≤5 × ULN for subjects with liver
metastases)
Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for
subjects with total bilirubin >1.5 × ULN if no
liver metastases or <3 × ULN in the presence of
documented Gilbert’s syndrome (unconjugated
hyperbilirubinemia) or liver metastases at
baseline
a Cockcroft-Gault equation:
Creatinine clearance (mL/min) = [140 - age (years)] × weight (kg)
72 × serum creatinine (mg/dL) {× 0.85 for female
subjects}
Note: This table includes eligibility-defining laboratory value requirements for
treatment; laboratory value requirements should be adapted according to local
regulations and guidelines for the administration of specific chemotherapies.
qualification procedures.
2. Adults ≥18 years or the minimum legal adult age (whichever is greater) at the time of informed
consent. (Follow local regulatory requirements if the legal age of adult voluntary consent for
study participation is >18 years old.)
3. Histologically documented NSCLC that meets all of the following criteria:
a. Stage IIIB or IIIC disease and not candidates for surgical resection or definitive
chemoradiation, or Stage IV NSCLC disease at the time of randomization (based on the
American Joint Committee on Cancer, Eighth Edition).
b. Documented negative test results for EGFR, ALK, and ROS1 actionable genomic
alterations based on analysis of tumor tissue. If test results for EGFR, ALK, and ROS1 are
not available, subjects are required to undergo testing performed locally for these genomic
alterations.
c. No known actionable genomic alterations in NTRK, BRAF, RET, MET, or other
actionable driver kinases with locally approved therapies. (Testing for genomic alterations
besides EGFR, ALK, and ROS1 is not required prior to enrollment.)
4. Has provided a formalin-fixed tumor tissue sample (minimum of 10 [preferably 15] × 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.
5. Tumor has high PD-L1 expression (TPS ≥50%) as determined by PD-L1 IHC 22C3 pharmDx
assay by central testing (minimum of 6 slides).
6. Has an adequate treatment washout period before Cycle 1 Day 1 defined as:
Treatment Washout Period
Major surgery ≥3 weeks
Radiation therapy including
palliative radiation to chest
≥4 weeks (a 2-week washout period is permitted
for palliative radiation to non-central nervous
system disease)
No more than 30Gys in lung fields in the past
6 months
7. Measurable disease based on local imaging assessment using RECIST Version 1.1.
8. Has left ventricular ejection fraction (LVEF) ≥50% by either an echocardiogram (ECHO) or
multigated acquisition scan (MUGA) within 28 days before randomization.
9. ECOG PS of 0 or 1 at screening.
10. Has a life expectancy of at least 3 months.
11. Adequate bone marrow function within 7 days before randomization defined as:
Parameter Laboratory Value
Bone Marrow Function
Platelet count ≥100,000/mm3
(platelet transfusion is not allowed
within 1 week prior to screening assessment)
Hemoglobin ≥9.0 g/dL (criteria must be met without packed
red blood cell/plasma transfusion within 2 weeks
prior to screening assessment. Subjects can be on
stable dose of erythropoietin [≥ approximately
3 months])
Absolute neutrophil count ≥1500/mm3
(granulocyte-colony stimulating
factor administration is not allowed within
1 week prior to screening assessment)
Blood Clotting Function
International normalized
ratio/prothrombin time and
activated partial thromboplastin
time or partial thromboplastin
time
≤1.5 × upper limit of normal (ULN) unless
subject is receiving anticoagulant therapy as long
as prothrombin time or activated partial
thromboplastin time is within therapeutic range of
intended use of anticoagulants
Renal Function
Creatinine clearance ≥30 mL/min, as calculated using the CockcroftGault equationa
Hepatic Function
Alanine
aminotransferase/aspartate
aminotransferase
≤2.5 × ULN (≤5 × ULN for subjects with liver
metastases)
Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ULN for
subjects with total bilirubin >1.5 × ULN if no
liver metastases or <3 × ULN in the presence of
documented Gilbert’s syndrome (unconjugated
hyperbilirubinemia) or liver metastases at
baseline
a Cockcroft-Gault equation:
Creatinine clearance (mL/min) = [140 - age (years)] × weight (kg)
72 × serum creatinine (mg/dL) {× 0.85 for female
subjects}
Note: This table includes eligibility-defining laboratory value requirements for
treatment; laboratory value requirements should be adapted according to local
regulations and guidelines for the administration of specific chemotherapies.
Exclusion Criteria
1. Has received prior systemic treatment for advanced or metastatic NSCLC.
2. Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant
setting:
a. Any agent, including an antibody-drug conjugate, containing a chemotherapeutic agent
targeting topoisomerase I.
b. TROP2-targeted therapy.
c. 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).
d. Any other immune checkpoint inhibitors.
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/metastatic disease.
3. Has spinal cord compression or active and untreated central nervous system (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 4 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 computed tomography (CT) scan or magnetic
resonance imaging (MRI) scan of the brain at baseline (MRI preferred) is required for all
subjects. For those subjects in whom CNS metastases are first discovered at the time of
screening, the treating Investigator should consider delay of study treatment to document
stability of CNS metastases with repeat imaging at least 4 weeks later (in which case, repeat of
all screening activity may be required).
4. Has received prior radiotherapy ≤4 weeks of start of study intervention or more than 30Gy to
the lung within 6 months of Cycle 1 Day 1. Subjects must have recovered from all radiationrelated toxicities, not require corticosteroids, and not have had radiation pneumonitis. A
2-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS
disease.
5. 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.
6. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required
steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled
out by imaging at screening.
7. Clinically severe pulmonary compromise 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.
8. Uncontrolled or significant cardiovascular disease, including:
a. 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).
b. Myocardial infarction within 6 months prior to randomization.
c. Uncontrolled angina pectoris within 6 months prior to randomization.
d. LVEF <50% by ECHO or MUGA scan within 28 days before randomization.
e. New York Heart Association Class 2 to 4 congestive heart failure (CHF) at screening.
Subjects 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.
f. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood
pressure >110 mmHg) within 28 days before randomization.
9. Clinically significant corneal disease.
10. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of
study drug. 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,
and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus
vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are liveattenuated vaccines and are not allowed. For any subject receiving an approved severe acute
respiratory syndrome coronavirus 2 (SARS-CoV2) 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 related to the vaccine (including hypersensitivity or allergies).
11. Active, known, or suspected autoimmune disease (has an active autoimmune disease that has
required systemic treatment in the past 2 years [ie, with use of systemic disease-modifying
agents, corticosteroids or immunosuppressive drugs]). Replacement therapy (eg, thyroxine,
insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed. Inhaled,
intranasal, intraocular, intra-articular, or topical steroids and adrenal replacement steroids are
permitted in the absence of active autoimmune disease.
12. 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.
13. Has known human immunodeficiency virus (HIV) infection that is not well controlled. All of
the following criteria are required to define an HIV infection that is well controlled:
undetectable viral RNA load, CD4+ counts/levels >350, no history of AIDs-defining
opportunistic infection within the past 12 months, and stable for at least 4 weeks on same antiHIV retroviral medications. If an HIV infection meets the above criteria, monitoring of the
subjects’ viral RNA load as well as the CD4+ count levels would be important. Subjects
should be tested for HIV prior to Cycle 1 Day 1 if required by local regulations or institutional review board (IRB)/ethics committee (EC). Note: Participants should remain on anti-viral
therapy throughout study intervention and follow local guidelines for HIV anti-viral therapy
post-completion of study intervention.
14. Has an active hepatitis or uncontrolled hepatitis B or active hepatitis C infection; is positive for
hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis b
surface antigen, anti-HBs, anti-HBc, or hepatitis B virus [HBV] DNA) or hepatitis C virus
(HCV RNA) infection. Subjects who have received hepatitis B vaccination with only anti-HBs
positivity and no clinical signs of hepatitis, and subjects who have been curatively treated for
hepatitis C infection as demonstrated clinically and by viral serologies will be eligible.
Participants who are hepatitis b surface antigen positive are eligible if they have received HBV
anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to
randomization. Note: Participants should remain on anti-viral therapy throughout study
intervention and follow local guidelines for HBV anti-viral therapy post-completion of study
intervention.
15. Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. Note: Subjects
with localized fungal infections of skin or nails are eligible.
16. Had an allogeneic tissue/solid organ transplant.
17. Has a history of severe hypersensitivity reactions to either the drug substances or inactive
ingredients (including but not limited to polysorbate 80) of Dato-DXd or pembrolizumab.
2. Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant
setting:
a. Any agent, including an antibody-drug conjugate, containing a chemotherapeutic agent
targeting topoisomerase I.
b. TROP2-targeted therapy.
c. 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).
d. Any other immune checkpoint inhibitors.
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/metastatic disease.
3. Has spinal cord compression or active and untreated central nervous system (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 4 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 computed tomography (CT) scan or magnetic
resonance imaging (MRI) scan of the brain at baseline (MRI preferred) is required for all
subjects. For those subjects in whom CNS metastases are first discovered at the time of
screening, the treating Investigator should consider delay of study treatment to document
stability of CNS metastases with repeat imaging at least 4 weeks later (in which case, repeat of
all screening activity may be required).
4. Has received prior radiotherapy ≤4 weeks of start of study intervention or more than 30Gy to
the lung within 6 months of Cycle 1 Day 1. Subjects must have recovered from all radiationrelated toxicities, not require corticosteroids, and not have had radiation pneumonitis. A
2-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS
disease.
5. 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.
6. Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required
steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled
out by imaging at screening.
7. Clinically severe pulmonary compromise 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.
8. Uncontrolled or significant cardiovascular disease, including:
a. 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).
b. Myocardial infarction within 6 months prior to randomization.
c. Uncontrolled angina pectoris within 6 months prior to randomization.
d. LVEF <50% by ECHO or MUGA scan within 28 days before randomization.
e. New York Heart Association Class 2 to 4 congestive heart failure (CHF) at screening.
Subjects 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.
f. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood
pressure >110 mmHg) within 28 days before randomization.
9. Clinically significant corneal disease.
10. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of
study drug. 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,
and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus
vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are liveattenuated vaccines and are not allowed. For any subject receiving an approved severe acute
respiratory syndrome coronavirus 2 (SARS-CoV2) 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 related to the vaccine (including hypersensitivity or allergies).
11. Active, known, or suspected autoimmune disease (has an active autoimmune disease that has
required systemic treatment in the past 2 years [ie, with use of systemic disease-modifying
agents, corticosteroids or immunosuppressive drugs]). Replacement therapy (eg, thyroxine,
insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) is not considered a form of systemic treatment and is allowed. Inhaled,
intranasal, intraocular, intra-articular, or topical steroids and adrenal replacement steroids are
permitted in the absence of active autoimmune disease.
12. 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.
13. Has known human immunodeficiency virus (HIV) infection that is not well controlled. All of
the following criteria are required to define an HIV infection that is well controlled:
undetectable viral RNA load, CD4+ counts/levels >350, no history of AIDs-defining
opportunistic infection within the past 12 months, and stable for at least 4 weeks on same antiHIV retroviral medications. If an HIV infection meets the above criteria, monitoring of the
subjects’ viral RNA load as well as the CD4+ count levels would be important. Subjects
should be tested for HIV prior to Cycle 1 Day 1 if required by local regulations or institutional review board (IRB)/ethics committee (EC). Note: Participants should remain on anti-viral
therapy throughout study intervention and follow local guidelines for HIV anti-viral therapy
post-completion of study intervention.
14. Has an active hepatitis or uncontrolled hepatitis B or active hepatitis C infection; is positive for
hepatitis B or C virus based on the evaluation of results of tests for hepatitis B (hepatitis b
surface antigen, anti-HBs, anti-HBc, or hepatitis B virus [HBV] DNA) or hepatitis C virus
(HCV RNA) infection. Subjects who have received hepatitis B vaccination with only anti-HBs
positivity and no clinical signs of hepatitis, and subjects who have been curatively treated for
hepatitis C infection as demonstrated clinically and by viral serologies will be eligible.
Participants who are hepatitis b surface antigen positive are eligible if they have received HBV
anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior to
randomization. Note: Participants should remain on anti-viral therapy throughout study
intervention and follow local guidelines for HBV anti-viral therapy post-completion of study
intervention.
15. Has an uncontrolled infection requiring IV antibiotics, antivirals, or antifungals. Note: Subjects
with localized fungal infections of skin or nails are eligible.
16. Had an allogeneic tissue/solid organ transplant.
17. Has a history of severe hypersensitivity reactions to either the drug substances or inactive
ingredients (including but not limited to polysorbate 80) of Dato-DXd or pembrolizumab.
The Estimated Number of Participants
-
Taiwan
42 participants
-
Global
740 participants
