Clinical Trials /

Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05)

NCT04484142

Description:

This is a study of the efficacy, pharmacokinetics, and safety of DS-1062a in participants with advanced or metastatic non-small cell lung cancer (NSCLC) with known actionable genomic alterations.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations (TROPION-Lung05)
  • Official Title: Phase 2, Single-arm, Open-label Study of DS-1062a in Advanced or Metastatic Non-small Cell Lung Cancer With Actionable Genomic Alterations and Progressed on or After Kinase Inhibitor Therapy and Platinum Based Chemotherapy (TROPION-Lung05)

Clinical Trial IDs

  • ORG STUDY ID: DS1062-A-U202
  • SECONDARY ID: 2020-002774-27
  • NCT ID: NCT04484142

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
DS-1062aDS-1062a 6.0 mg/kg

Purpose

This is a study of the efficacy, pharmacokinetics, and safety of DS-1062a in participants with advanced or metastatic non-small cell lung cancer (NSCLC) with known actionable genomic alterations.

Detailed Description

      This study will evaluate DS-1062a 6.0 mg/kg in participants with advanced or metastatic NSCLC
      with actionable genomic alterations and who have been previously been treated with 1 or more
      kinase inhibitors and platinum-based chemotherapy. The study will be divided into 3 periods:
      Screening Period, Treatment Period, and Follow-up Period. The primary analysis of Objective
      Response Rate (ORR) by blinded Independent Central Review (BICR) will be conducted after all
      participants either have been followed for at least 9 months after the start of study
      treatment or have discontinued from the study, whichever occurs first.
    

Trial Arms

NameTypeDescriptionInterventions
DS-1062a 6.0 mg/kgExperimentalParticipants will receive 6.0 mg/kg of DS-1062a
  • DS-1062a

Eligibility Criteria

        Inclusion Criteria:

        Participants eligible for inclusion in the study must meet all inclusion criteria for this
        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)

          -  Has pathologically documented NSCLC that:

               1. Has stage IIIB or stage IV NSCLC disease at the time of enrollment (based on the
                  American Joint Committee on Cancer, Eighth Edition).

               2. Has one or more of the following documented activating genomic alterations: EGFR,
                  ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET.

        Overexpression of any of the above, in the absence of activating mutations, is NOT
        sufficient for enrollment

        Participants with EGFR genomic alterations should be evaluated for the presence of EGFR
        T790M mutation after relapse/progression on/after the most recent anti-EGFR TKI, unless
        already known to carry this mutation. Participants with EGFR mutations (regardless of T790M
        status) should comprise no less than 40% and no more than 50% of participants by the
        conclusion of study enrollment.

          -  Has documentation of radiographic disease progression while on or after receiving the
             most recent treatment regimen for advanced or metastatic NSCLC.

          -  Participant must meet at least the following for advanced or metastatic NSCLC:

               1. Has progressed on or after at least one kinase inhibitor as specified in the
                  study protocol

               2. Has progressed on or after at least 1 regimen of platinum-based chemotherapy

        Up to 4 prior lines of therapy are allowed to be eligible for this study

          -  Willing and able to undergo a mandatory pre-treatment tumor biopsy

          -  Measurable disease based on local imaging assessment using RECIST v1.1.

          -  Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 - 1 at screening.

        Exclusion Criteria:

        Participants meeting any exclusion criteria for this study will be excluded from this
        study.

          -  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.

          -  Has leptomeningeal carcinomatosis.

          -  Has prior treatment with:

               1. Any agent including antibody drug conjugate (ADC) containing a chemotherapeutic
                  agent targeting topoisomerase I.

               2. TROP2-targeted therapy.

          -  Uncontrolled or significant cardiovascular disease:

               1. History of myocardial infarction within 6 months prior to Cycle 1 Day 1.

               2. History of uncontrolled angina pectoris within 6 months prior to Cycle 1 Day 1.

               3. Symptomatic 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 of Cycle 1 Day 1) in order to be eligible.

               4. History of serious cardiac arrhythmia requiring treatment.

               5. LVEF <50% or institutional lower limit of normal by ECHO or MUGA scan.

               6. Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic
                  blood pressure >110 mmHg).

          -  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

          -  Clinically significant corneal disease.

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

Primary Outcome Measures

Measure:Objective Response Rate (ORR) As Assessed by Blind Independent Central Review Per RECIST v1.1 Following DS-1062a Intravenous Infusion
Time Frame:From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months
Safety Issue:
Description:ORR is defined as the proportion of participants with a best overall response of confirmed complete response (CR) or confirmed partial response (PR). CR is defined as a disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of diameters of target lesions.

Secondary Outcome Measures

Measure:Duration of Response (DOR) As Assessed by Blinded Independent Central Review and by Investigator Per RECIST v1.1 Following DS-1062a Intravenous Infusion
Time Frame:From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months
Safety Issue:
Description:DOR is defined as the time from the date of the first documentation of response (confirmed CR or confirmed PR) to the date of the first documentation of PD or death due to any cause, whichever occurs first.
Measure:Progression-free Survival (PFS) As Assessed by Blinded Independent Central Review and by Investigator Per RECIST v1.1 Following DS-1062a Intravenous (IV) Infusion
Time Frame:From baseline until disease progression, death, or other protocol defined reason, up to approximately 23 months
Safety Issue:
Description:PFS is defined as the time from the start of study treatment to the earlier of the dates of the first documentation of progressive disease or death due to any cause.
Measure:Overall Survival (OS) Following DS-1062a Intravenous Infusion
Time Frame:From baseline until death due to any cause, up to approximately 23 months
Safety Issue:
Description:OS is defined as the time from the start of study treatment to the date of death due to any cause.
Measure:Percentage of Participants Who Reported Treatment-emergent Adverse Events Following DS-1062a Intravenous Infusion in Participants with Advanced or Metastatic NSCLC with Actionable Genomic Alterations
Time Frame:From baseline up to approximately 23 months post treatment
Safety Issue:
Description:Reported treatment-emergent adverse events, serious adverse events, adverse events of interest, and those considered related to the study drug or study procedures, or that associated DS-1062a reduction, interruption, or discontinuation.
Measure:Pharmacokinetic Parameter Maximum Concentration (Cmax) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a
Time Frame:Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days)
Safety Issue:
Description:
Measure:Pharmacokinetic Parameter Time to Maximum Concentration (Tmax) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a
Time Frame:Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days)
Safety Issue:
Description:
Measure:Pharmacokinetic Parameter Area Under the Concentration-Time Curve (AUC) of DS-1062a, Total Anti-TROP2 Antibody, and MAAA-1181a
Time Frame:Cycle 1, Day 1: predose (within 8 hours [h] of infusion), 30 minutes (min), 3 h, 5 h, 7 h postdose; Cycle 1, Day 2, Day 4, Day 8, and Day 15 postdose; Cycle 2 and Cycle 3, Day 1 predose (within 8 h) and postdose (within 1 h) (each cycle is 21 days)
Safety Issue:
Description:AUC up to the last quantifiable time (AUClast) and AUC during dosing interval (AUCtau) will be assessed for DS-1062, total Anti-TROP2 antibody, and MAAA-1181a.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • Metastatic Non-small Cell Lung Cancer
  • Advanced Metastatic Non-small Cell Lung Cancer
  • Non-small Cell Lung Cancer
  • DS-1062a

Last Updated

June 11, 2021