Clinical Trials /

DS-1062a in Combination With Durvalumab in Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung04)

NCT04612751

Description:

This study will assess safety, tolerability, and treatment activity of DS-1062a in combination with durvalumab in participants with advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations who have had previously treated with platinum-based therapy with or without prior immunotherapy.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: DS-1062a in Combination With Durvalumab in Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung04)
  • Official Title: A Phase 1b, Multicenter, 2-Part, Open-Label Study of DS-1062a in Combination With Durvalumab in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations and Previously Treated With Platinum-based Chemotherapy With or Without Prior Immunotherapy (TROPION-Lung04)

Clinical Trial IDs

  • ORG STUDY ID: DS1062-A-U104
  • NCT ID: NCT04612751

Conditions

  • Advanced or Metastatic NSCLC

Interventions

DrugSynonymsArms
DS-1062aDS-1062a
DurvalumabDS-1062a

Purpose

This study will assess safety, tolerability, and treatment activity of DS-1062a in combination with durvalumab in participants with advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations who have had previously treated with platinum-based therapy with or without prior immunotherapy.

Detailed Description

      This study will assess safety, tolerability, and treatment activity of DS-1062a in
      combination with durvalumab in participants with advanced or metastatic NSCLC without
      actionable genomic alterations and who have been previously treated with at least 1 regimen
      of platinum-based chemotherapy and at least 1 regimen of programmed cell death 1
      (PD-1)/programmed cell death ligand 1 (PD-L1)- directed immunotherapy, either in combination
      or sequentially. Participants with a documented PD-L1 tumor proportion score of <1% must have
      been previously treated with at least 1 regimen of platinum-based chemotherapy with or
      without PD-1/PD-L1 immunotherapy.
    

Trial Arms

NameTypeDescriptionInterventions
DS-1062aExperimentalDose Escalation and Dose Expansion: DS-1062 in combination with durvalumab in participants with advanced or metastatic NSCLC without actionable genomic alterations and previously treated with platinum-based chemotherapy with or without prior immunotherapy.
  • DS-1062a
  • Durvalumab

Eligibility Criteria

        Inclusion Criteria:

          -  Advanced or metastatic NSCLC, histologically confirmed at diagnosis of NSCLC,
             documented negative test results for EGFR and ALK genomic alterations, and no known
             genomic alterations in ROS1, NTRK, BRAF, or other driver oncogenes with approved
             therapies (actionable genomic alterations).

          -  Documentation of radiological disease progression while on or after receiving the most
             recent treatment regimen for advanced or metastatic NSCLC.

          -  Received at least 1 regimen of platinum-based chemotherapy and have at least 1 regimen
             of PD-1/PD-L1 directed immunotherapy, either in combination or sequentially.
             Participants with a documented PD-L1 tumor proportion score of <1% must have been
             previously treated with at least 1 regimen of platinum-based chemotherapy with or
             without prior PD-1/PD-L1 immunotherapy.

          -  Willing and able to undergo a mandatory tumor biopsy.

          -  Archival tumor tissue from initial diagnosis, to the extent that archival tumor tissue
             is available, for measurement of TROP2 expression levels or other biomarkers.

          -  Has adequate bone marrow reserve and organ function at baseline within 7 days prior to
             Cycle 1 Day 1

        Exclusion Criteria:

          -  Experienced grade 3 or higher immune-related adverse events with prior immunotherapy
             treatment

          -  Received a live vaccine within 30 days prior to the first dose of study treatment.

          -  Active, known, or suspected autoimmune disease.

          -  Has a condition requiring systemic treatment with either corticosteroids (>10 mg daily
             prednisone equivalent) or other immunosuppressive medications within 14 days of Cycle
             1 Day 1.

          -  Prior allogenic organ transplantation

          -  Known allergy or history of severe hypersensitivity reactions to either the drug
             substances or inactive ingredients (including but not limited to polysorbate 80)

          -  Uncontrolled or significant cardiac disease

          -  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.

          -  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.

          -  Has other primary malignancies, except adequately resected nonmelanoma skin cancer,
             curatively treated in situ disease, or other solid tumors curatively treated, with no
             evidence of disease for >5 years.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting Toxicities (Dose Escalation)
Time Frame:Baseline up to Cycle 1 (Days 1 to 21)
Safety Issue:
Description:Dose-limiting toxicities and the maximum tolerated dose (MTD) will be determined in the study population treated with DS-1062a in combination with durvalumab.

Secondary Outcome Measures

Measure:Objective Response Rate (Dose Escalation and Dose Expansion)
Time Frame:Baseline up to best overall response (confirmed complete response or partial response), up to approximately 24 months postdose
Safety Issue:
Description:
Measure:Duration of Response (Dose Escalation and Dose Expansion)
Time Frame:From first objective response (confirmed complete response or partial response) to progressive disease or death (whichever occurs first), up to approximately 24 months postdose
Safety Issue:
Description:
Measure:Disease Control Rate (Dose Escalation and Dose Expansion)
Time Frame:Baseline up to objective response (confirmed complete response, partial response, or stable disease), up to 24 months postdose
Safety Issue:
Description:
Measure:Clinical Benefit Rate (Dose Escalation and Dose Expansion)
Time Frame:Baseline up to objective response (confirmed complete response, partial response, or stable disease of at least 180 days), up to 24 months postdose
Safety Issue:
Description:
Measure:Progression-free Survival (Dose Escalation and Dose Expansion)
Time Frame:Baseline up progressive disease or death (whichever occurs first), up to approximately 24 months postdose
Safety Issue:
Description:
Measure:Time to Response (Dose Escalation and Dose Expansion)
Time Frame:Baseline up to first objective response (confirmed complete response or partial response), up to approximately 24 months postdose
Safety Issue:
Description:
Measure:Percentage Change in the Sum of Diameters of Measurable Tumors (Dose Escalation and Dose Expansion)
Time Frame:Baseline up to approximately 24 months postdose
Safety Issue:
Description:
Measure:Overall Survival (Dose Escalation and Dose Expansion)
Time Frame:Baseline up to death (any cause), up to approximately 24 months postdose
Safety Issue:
Description:
Measure:Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of DS-1062a, Total anti-TROP2 antibody, and MAAA-1181a (Dose Escalation and Dose Expansion)
Time Frame:DS-1062a, Cycle 1 and 3: Day 1 predose, 30 minutes, 3 hours (h), 5 h, 7 h postdose and Days 2, 4, 8, and 15; Cycle 2, 4 and 8, Day 1 pre and 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 MAAA-1181a (Dose Escalation and Dose Expansion)
Time Frame:DS-1062a, Cycle 1 and 3: Day 1 predose, 30 minutes, 3 hours (h), 5 h, 7 h postdose and Days 2, 4, 8, and 15; Cycle 2, 4 and 8, Day 1 pre and 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 MAAA-1181a (Dose Escalation and Dose Expansion)
Time Frame:DS-1062a, Cycle 1 and 3: Day 1 predose, 30 minutes, 3 hours (h), 5 h, 7 h postdose and Days 2, 4, 8, and 15; Cycle 2, 4 and 8, Day 1 pre and 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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • Advanced or Metastatic NSCLC
  • DS-1062a
  • Durvalumab

Last Updated

November 9, 2020