Clinical Trials /

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

NCT04656652

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: DS1062-A-U301
  • SECONDARY ID: 2020-004643-80
  • NCT ID: NCT04656652

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
DS-1062aDatopotamab deruxtecan (Dato-DXd)DS-1062a 6.0 mg/kg
DocetaxelDocetaxel 75 mg/m^2

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
DS-1062a 6.0 mg/kgExperimentalParticipants will be randomized to receive 6.0 mg/kg of DS-1062a.
  • DS-1062a
Docetaxel 75 mg/m^2Active ComparatorParticipants will be randomized to receive 75 mg/m^2 docetaxel.
  • Docetaxel

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:ORR is defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR).
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:DCR is defined as the proportion of participants who achieved a best overall response (BOR) of CR, PR, or stable disease (SD).
Measure: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
Safety Issue:
Description:TTR is defined as the time from randomization to the date of the first documentation of objective response (CR or PR) in responding participants.
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • Metastatic Non-small Cell Lung Cancer
  • Advanced Non-small Cell Lung Cancer
  • Non-small Cell Lung Cancer
  • DS-1062
  • Docetaxel
  • Datopotamab Deruxtecan (Dato-DXd)

Last Updated

May 12, 2021