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
975
Interventional
randomized controlled trial
open(masking not used)
active control
parallel assignment
treatment purpose
-Sign and date the Main Informed Consent Form (ICF), prior to the start of any study- specific qualification procedures.
-Adults >=18 at the time the Main ICF is signed.
-Has tumor with PD-L1 TPS <50% as determined by PD-L1 IHC 22C3 pharmDx assay by central testing.
-Has provided a formalin-fixed tumor tissue sample for the measurement of TROP2 protein expression and for the assessment of other exploratory biomarkers.
-Has not been treated with systemic anticancer therapy for advanced or metastatic non-squamous NSCLC.
-Has measurable disease based on local imaging assessment using RECIST v1.1.
-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 epidermal growth factor receptor (EGFR), lymphoma kinase (ALK), and proto-oncogene1 (ROS1) actionable genomic alterations based on analysis of tumor tissue.
c.No known actionable genomic alterations in neurotrophic tyrosine receptor kinase (NTRK), proto-oncogene B-raf (BRAF), rearranged during transfection (RET), mesenchymal-epithelial transition factor (MET), or other actionable driver kinases with locally approved therapies.
-Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at screening.
-Has an adequate treatment washout period before Cycle 1 Day 1.
-Is willing and able to participate in the collection of patient-reported outcomes (PRO) data.
-Has received prior systemic treatment for advanced/metastatic NSCLC.
-Has received prior treatment with any of the following, including in the adjuvant/neoadjuvant (for NSCLC) 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.
-Has received a live vaccine or live-attenuated vaccine 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.
-Has spinal cord compression or clinically active untreated central nervous system (CNS) metastases and/or carcinomatous meningitis.
-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.
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.
f.Uncontrolled hypertension within 28 days before randomization.
-Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses.
-Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
-History of another primary malignancy (beyond NSCLC) except for:
a.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.
b.Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
c.Adequately treated carcinoma in situ without evidence of disease.
d.Participants with a history of prostate cancer (tumor/node/metastasis stage) of Stage <=T2cN0M0 without biochemical recurrence or progression.
-Has a history of severe hypersensitivity reactions to either the drugs or inactive ingredients of Dato-DXd, pembrolizumab, carboplatin, cisplatin or pemetrexed.
-Has a history of severe hypersensitivity reactions to other monoclonal antibodies.
-Has known human immunodeficiency virus (HIV) infection that is not well controlled.
-Has active or uncontrolled hepatitis B or C infection.
-Female who is pregnant or breastfeeding or intends to become pregnant.
-Any other medical conditions, including cardiac disease or psychological disorders, and/or substance abuse.
-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.
-Has active, known, or suspected autoimmune disease.
-Has clinically significant corneal disease.
-Has had an allogeneic tissue/solid organ transplantation.
-Has received prior radiotherapy <=4 weeks of start of study intervention or more than 30 Gy to the lung within 6 months of Cycle 1 Day 1.
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
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/
