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 <50% Non-squamous Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung07)
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 Non-squamous Non-Small Cell Lung Cancer (TROPION-Lung07)
Inoguchi Akihiro
DAIICHI SANKYO Co.,Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
Contact for Clinical Trial Information
DAIICHI SANKYO Co.,Ltd.
1-2-58, Hiromachi, Shinagawa-ku, Tokyo
+81-3-6225-1111
dsclinicaltrial@daiichisankyo.co.jp
Recruiting
Jan. 01, 2023
Dec. 27, 2022
1170
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
- 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 x 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.
- 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):
a. Any agent, including an ADC, containing a chemotherapeutic agent targeting topoisomerase I
b. TROP2-targeted therapy
c. 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)
d. 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-Guerin (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:
a. 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).
b. Myocardial infarction within 6 months prior to Cycle 1 Day 1.
c. History of a serious cardiac arrhythmia requiring treatment
d. Uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.
e. Left ventricular ejection fraction (LVEF) <50% by echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before randomization.
f. 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.
g. 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, Sjogren's syndrome, sarcoidosis, etc), or prior complete pneumonectomy.
18age old over
No limit
Both
Non-small Cell Lung Cancer
Drug: DS-1062a
DS-1062a will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle. (6.0 mg/kg)
Drug: Pembrolizumab
Pembrolizumab will be administered as an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle. (fixed pembrolizumab dose 200 mg Q3W)
Drug: Carboplatin
Carboplatin will be administered an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for a maximum of 4 cycles. (AUC 5)
Drug: Cisplatin
Cisplatin will be administered an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle for a maximum of 4 cycles. (75 mg/m^2)
Drug: Pemetrexed
Pemetrexed will be administered an intravenous (IV) infusion every 3 weeks on Day 1 of each 21-day cycle. (500 mg/m^2)
1.Progression-free Survival as assessed by blinded independent central review (BICR) per RECIST v1.1
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.
2.Overall Survival
Overall Survival (OS) is defined as the time from randomization to death due to any cause.
1. Objective Response Rate by Blinded Independent Central Review in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)
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 With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)
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. Objective Response Rate by Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)
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.
4. Duration of Response by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)
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.
5. Time to Response by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)
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.
6. Disease Control Rate by BICR and Investigator in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)
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.
7. Progression-free Survival 2 in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)
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
8. Time to Deterioration in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)
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) in Participants With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC)
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.
The immunogenicity of Dato-DXd in combination with pembrolizumab will be assessed.
DAIICHI SANKYO Co.,Ltd.
AstraZeneca
Applicable
Merck Sharp & Dohme Corp.
Applicable
National Hospital Organization Iwakuni Clinical Center IRB
1-1-1, Atagomachi, Iwakuni,, Yamaguchi
+81-827-34-1000
Approval
Oct. 06, 2022
Yes
De-identified individual participant data (IPD) on completed studies 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 Information:
-Study Protocol
-Statistical Analysis Plan (SAP)
-Informed Consent Form (ICF)
Time Frame: Completed studies that has reached a global end or completion with all data set collected and analyzed, and 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 on completed 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/
