Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-LUNG01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04656652
Recruitment Status : Recruiting
First Posted : December 7, 2020
Last Update Posted : October 13, 2021
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Brief Summary:
This study will evaluate the efficacy, safety, and pharmacokinetics of DS-1062a versus docetaxel in participants with previously treated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations.

Condition or disease Intervention/treatment Phase
Non-small Cell Lung Cancer Drug: DS-1062a Drug: Docetaxel Phase 3

Detailed Description:
This study will evaluate DS-1062a 6.0 mg/kg vs docetaxel 75 mg/m^2 in participants with advanced or metastatic NSCLC without actionable genomic alterations and who have been previously treated with platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody, either in combination or sequentially. The study will be divided into 3 periods: Screening Period, Treatment Period, and Follow-up Period.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 590 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 3 Randomized Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-LUNG01)
Actual Study Start Date : December 21, 2020
Estimated Primary Completion Date : October 27, 2022
Estimated Study Completion Date : June 27, 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

Arm Intervention/treatment
Experimental: DS-1062a 6.0 mg/kg
Participants will be randomized to receive 6.0 mg/kg of DS-1062a.
Drug: DS-1062a
DS-1062a will be administered as an intravenous (IV) infusion on Day 1 of each 3-week cycle
Other Name: Datopotamab deruxtecan (Dato-DXd)

Active Comparator: Docetaxel 75 mg/m^2
Participants will be randomized to receive 75 mg/m^2 docetaxel.
Drug: Docetaxel
Docetaxel will be administered as an IV infusion on Day 1 of each 3-week cycle.




Primary Outcome Measures :
  1. Progression-free Survival (PFS) As Assessed by Blinded Independent Central Review (BICR) Per RECIST v1.1 Following DS-1062a Versus Docetaxel [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months ]
    PFS is defined as the time from randomization to the earlier of the dates of the first documentation of radiographic progressive disease or death due to any cause.

  2. Overall Survival (OS) Following DS-1062a Versus Docetaxel [ Time Frame: From randomization until date of death due to any cause, up to approximately 43 months ]
    OS is defined as the time from randomization to the date of death due to any cause.


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) As Assessed by Investigator Per RECIST v1.1 Following DS-1062a Versus Docetaxel [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months ]
    PFS is defined as the time from randomization to the earlier of the dates of the first documentation of radiographic progressive disease or death due to any cause.

  2. Objective Response Rate (ORR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months ]
    ORR is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR).

  3. Duration of Response (DOR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel [ 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 43 months ]
    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 documentation of radiographic PD or death due to any cause, whichever occurs first.

  4. Disease Control Rate (DCR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel [ Time Frame: From randomization until disease progression or death (whichever occurs first), up to approximately 43 months ]
    DCR is defined as the proportion of participants who achieved a best overall response (BOR) of CR, PR, or stable disease (SD).

  5. Time to Response (TTR) As Assessed by Blinded Independent Central Review (BICR) and Investigator As Per RECIST v1.1 Following DS-1062a Versus Docetaxel [ Time Frame: From randomization to date of first objective response (CR or PR), up to approximately 43 months ]
    TTR is defined as the time from randomization to the date of the first documentation of objective response (CR or PR) in responding participants.

  6. European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ) and EORTC Quality of Life Questionnaire (QLQ) for Lung Cancer Trials Scores (Except Questions 36 and 37) Following DS-1062a Versus Docetaxel [ Time Frame: Baseline and assessed on Day 15 of each cycle (only odd cycles after Cycle 4 for QLQ-C30) until disease progression or end of treatment (each cycle is 21 days) and then every 3 months until end of study, up to approximately 43 months ]
  7. Percentage of Participants Who Reported Treatment-emergent Adverse Events Following DS-1062a Versus Docetaxel [ Time Frame: Baseline up to 35 days after last study dose, up to approximately 43 months ]
    Reported treatment-emergent adverse events, serious adverse events, adverse events of special interest, and those considered related to the study drug or study procedures, or that are associated with study treatment reduction, interruption, or discontinuation.

  8. Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of DS-1062a, Total Anti-Trophoblast cell surface protein 2 (Anti-TROP2) Antibody, and Active Metabolite MAAA-1181a [ Time Frame: Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2, 3, 4, 6, and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days) ]
  9. Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of DS-1062a, Total Anti-TROP2 Antibody, and Active Metabolite MAAA-1181a [ Time Frame: Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2, 3, 4, 6, and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days) ]
  10. Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of DS-1062a, Total Anti-TROP2 Antibody, and Active Metabolite MAAA-1181a [ Time Frame: Cycle 1, Day 1: predose and 30 minutes, 3 hours, 5 hours, and 7 hours postdose and Days 2, 4, 8, and 15; Cycles 2, 3, 4, 6, and 8, Day 1: predose and 1 hour postdose (each cycle is 21 days) ]
    Area under the plasma concentration-time curve up to last quantifiable time (AUClast) and area under the plasma concentration-time curve during dosing interval (AUCtau) will be assessed.

  11. 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: Cycle 1, Day 1 predose; Cycle 1, Day 8; Cycles 2, 4, and subsequent cycles, Day 1 predose; end of treatment; 28-day safety follow up; and long-term survival follow up every 3 months, up to approximately 43 months (each cycle is 21 days) ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Participants eligible for inclusion in the study must meet all inclusion criteria within 28 days of randomization into the study.

  • Sign and date the inform consent form (ICF) prior to the start of any study specific qualification procedures.
  • Adults ≥18 years (if the legal age of consent is >18 years old, then follow local regulatory requirements)
  • Life expectancy ≥3 months
  • Has pathologically documented NSCLC that:

    1. Has stage IIIB, IIIC, or stage IV NSCLC disease at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition)
    2. Has documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)
    3. Has no known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto oncogene B-raf (BRAF), or other actionable driver oncogenes with approved therapies (actionable genomic alteration)
  • Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC
  • Participant must meet 1 of the following prior therapy requirements for advanced or metastatic NSCLC:

    1. Received platinum-based chemotherapy in combination with α-PD-1/α-PD-L1 monoclonal antibody as the only prior line of therapy

      • Includes participants who received prior platinum-based chemo/radiotherapy with maintenance α-PD-1/α-PD-L1 monoclonal antibody for Stage III disease and relapsed/progressed within 6 months from the last dose of platinum-based chemotherapy
      • Includes participants who received prior platinum-based chemo/radiotherapy (with or without maintenance α-PD-1/α-PD-L1 monoclonal antibody) for Stage III disease and subsequently received α-PD-1/α-PD-L1 monoclonal antibody therapy (with or without platinum-based chemotherapy) for recurrent disease
    2. Received platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy
  • Must undergo a mandatory pre-treatment tumor biopsy procedure or, if available, a tumor biopsy that was recently collected (within 3 months of Screening) after completion of the most recent anticancer treatment regimen and of adequate size may be substituted for the mandatory pre-treatment biopsy procedure collected during Screening.
  • Archival tumor tissue from initial diagnosis is required, to the extent that archival tumor tissue is available
  • Measurable disease based on local imaging assessment using RECIST v1.1
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening
  • Within 7 days before Cycle 1 Day 1, has adequate bone marrow, hepatic, and renal function
  • Left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before Cycle 1 Day 1
  • Adequate blood clotting function defined as international normalized ratio/prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤1.5 × upper limit of normal (ULN)
  • Adequate treatment washout period before Cycle 1 Day 1
  • Females of childbearing potential must have a negative serum pregnancy test at screening and must be willing to use highly effective birth control from the time of enrollment up to 7 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
  • Males must be surgically sterile or must use a condom in addition to highly effective birth control if his partners are of reproductive potential from the time of enrollment and for at least 4 months after last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
  • Male participants must not freeze or donate sperm from the time of Screening and throughout the study period and for at least 4 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel
  • Female participants must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study period and for at least 7 months after the last dose of DS-1062a and for at least 6 months after the last dose of docetaxel

Exclusion Criteria:

  • Mixed small-cell lung cancer (SCLC) and NSCLC histology
  • Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases who are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
  • Has leptomeningeal carcinomatosis or metastasis
  • Had prior treatment with:

    • Any agent including antibody drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase I
    • TROP2-targeted therapy
    • Docetaxel as monotherapy or in combination with other agents
  • Had prior treatment with platinum-based chemotherapy and prior immunotherapy for Stage II NSCLC disease (eg, in the neo-adjuvant or adjuvant setting) without subsequently meeting the prior therapy requirements for Stage III or metastatic NSCLC disease
  • Has NSCLC disease that is eligible for definitive local therapy alone
  • Uncontrolled or significant cardiovascular disease, including:

    • Mean QT interval corrected for heart rate using Fridericia's formula >470 msec (based on the average of Screening triplicate 12-lead electrocardiogram [ECG] determinations).
    • History of myocardial infarction within 6 months before Cycle 1 Day 1
    • History of uncontrolled angina pectoris within 6 months before Cycle 1 Day 1
    • Congestive heart failure (CHF) (New York Heart Association Class II to IV) at Screening. Participants 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 Cycle 1 Day 1) in order to be eligible.
    • History of serious cardiac arrhythmia requiring treatment
    • LVEF <50% by ECHO or MUGA scan within 28 days before Cycle 1 Day 1
    • Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) within 28 days before Cycle 1 Day 1
  • 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
  • Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of study 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 (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.
  • Significant third-space fluid retention (for example ascites or pleural effusion) and is not amenable for required repeated drainage.
  • Clinically significant corneal disease
  • Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections
  • Has known human immunodeficiency virus (HIV) infection that is not well controlled
  • Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1
  • Has other primary malignancies, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years.
  • Toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to NCI-CTCAE version 5.0 Grade ≤1 or baseline
  • Has other primary malignancies, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years
  • Has a history of severe hypersensitivity reactions to either the drug substances, inactive ingredients (including but not limited to polysorbate 80) of DS-1062a or docetaxel, or monoclonal antibodies
  • Pregnant or breastfeeding
  • Have substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04656652


Contacts
Layout table for location contacts
Contact: Daiichi Sankyo Contact for Clinical Trial Information 908-992-6400 CTRinfo@dsi.com

Locations
Show Show 198 study locations
Sponsors and Collaborators
Daiichi Sankyo, Inc.
AstraZeneca
Investigators
Layout table for investigator information
Study Director: Global Clinical Leader Daiichi Sankyo, Inc.
Layout table for additonal information
Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT04656652    
Other Study ID Numbers: DS1062-A-U301
2020-004643-80 ( EudraCT Number )
First Posted: December 7, 2020    Key Record Dates
Last Update Posted: October 13, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
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/

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daiichi Sankyo, Inc.:
Metastatic Non-small Cell Lung Cancer
Advanced Non-small Cell Lung Cancer
Non-small Cell Lung Cancer
DS-1062
Docetaxel
Datopotamab Deruxtecan (Dato-DXd)
Additional relevant MeSH terms:
Layout table for MeSH terms
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action