Clinical Trials /

Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung04)

NCT04612751

Description:

This study will assess safety, tolerability, and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with durvalumab in participants with advanced or metastatic non-small cell lung cancer (NSCLC).

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung04)
  • Official Title: A Phase 1b, Multicenter, 2-Part, Open-Label Study of Datopotamab Deruxtecan (Data-DXd) in Combination With Durvalumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung04)

Clinical Trial IDs

  • ORG STUDY ID: DS1062-A-U104
  • SECONDARY ID: 2021-000274-28
  • NCT ID: NCT04612751

Conditions

  • Advanced or Metastatic NSCLC

Interventions

DrugSynonymsArms
Datopotamab deruxtecanDato-DXdDatopotamab deruxtecan (Dato-DXd)
DurvalumabDatopotamab deruxtecan (Dato-DXd)
CarboplatinDatopotamab deruxtecan (Dato-DXd)
CisplatinDatopotamab deruxtecan (Dato-DXd)

Purpose

This study will assess safety, tolerability, and treatment activity of datopotamab deruxtecan (Dato-DXd) in combination with durvalumab in participants with advanced or metastatic non-small cell lung cancer (NSCLC).

Detailed Description

      The primary objective of this study will assess the safety and tolerability of datopotamab
      deruxtecan (Dato-DXd) in combination with durvalumab with or without 4 cycles of platinum
      chemotherapy in participants with advanced or metastatic NSCLC who have either been
      previously treated or are treatment naïve in a metastatic setting.

      Two dose levels of Dato-DXd (4.0 mg/kg and 6.0 mg/kg) will be studied in combination with
      1120 mg fixed dose of durvalumab, with or without 4 cycles of platinum chemotherapy in 6
      study cohorts. This study will be conducted sequentially and dose escalation will occur
      according to lower dose to higher dose in the same combination regimen (4.0 mg/kg to 6.0
      mg/kg) and from 2-drug combination (Dato-DXd and durvalumab) to 3-drug combination regimen
      (Dato-DXd, durvalumab, and carboplatin or cisplatin).
    

Trial Arms

NameTypeDescriptionInterventions
Datopotamab deruxtecan (Dato-DXd)ExperimentalDose Escalation and Dose Expansion: Datopotamab deruxtecan (Dato-DXd) in combination with durvalumab with and without platinum-based chemotherapy in participants with advanced or metastatic NSCLC.
  • Datopotamab deruxtecan
  • Durvalumab
  • Carboplatin
  • Cisplatin

Eligibility Criteria

        Inclusion Criteria:

          -  Men or women ≥20 years old in Japan, ≥18 years old in the United States on the day of
             signing the informed consent form (for the other countries, local regulatory
             requirements to consent should be followed)

          -  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, RET, MET, 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, if any, for advanced or metastatic NSCLC.

          -  Must meet the following prior therapy requirements for advanced or metastatic NSCLC:

               -  Dose escalation (all cohorts): Has received ≤ 2 lines of prior anticancer therapy
                  for advanced/metastatic disease

               -  Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with
                  1120 mg durvalumab Q3W): Has not received immune checkpoint inhibitor (ICI)
                  including PD-1/PD-L1, PD-L2, CTLA-4, and may or may not have been treated with
                  systemic chemotherapy for advanced or metastatic NSCLC

               -  Dose expansion (cohorts with 4.0 mg/kg or 6.0 mg/kg Dato-DXd in combination with
                  1120 mg durvalumab and 4 cycles of AUC 5 carboplatin or cisplatin 75 mg/m^2 Q3W):
                  ICI naïve and has not been treated with systemic anticancer therapy for advanced
                  or metastatic NSCLC.

          -  Willing and able to undergo a mandatory tumor biopsy. There is no requirement for
             PD-L1 protein expression for inclusion.

          -  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

          -  Has a history of severe hypersensitivity reactions to either the drug substances or
             inactive ingredients (including but not limited to polysorbate 80) of Dato-DXd or
             durvalumab, and carboplatin or cisplatin for participants to be enrolled in those
             relevant cohorts)

          -  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 a history of malignancy, other than NSCLC, except (a) adequately resected
             nonmelanoma skin cancer, (b) curatively treated in situ disease, or (c) 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 the National Cancer Institute Common Terminology
             Criteria for Adverse Events version 5.0 Grade ≤1 or baseline
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of Participants With Dose-limiting Toxicities and Treatment-emergent Adverse Events (Dose Escalation)
Time Frame:DLTs: Baseline up to Cycle 1 (Days 1 to 21); TEAEs: Baseline up to 90 days after last dose, up to approximately 30 months post-dose
Safety Issue:
Description:Dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD) will be determined in the study population treated with Dato-DXd 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 30 months post-dose
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 30 months post-dose
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 30 months post-dose
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 30 months post-dose
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 30 months post-dose
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 30 months post-dose
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 30 months post-dose
Safety Issue:
Description:
Measure:Overall Survival (Dose Escalation and Dose Expansion)
Time Frame:Baseline up to death (any cause), up to approximately 30 months post-dose
Safety Issue:
Description:
Measure:Pharmacokinetic Parameter Maximum Plasma Concentration (Cmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a (Dose Escalation and Dose Expansion)
Time Frame:Dato-DXd, Cycle 1 and 3: Day 1 pre-dose, 30 minutes, 3 hours, 5 hours, 7 hours post-dose and Days 2, 4, 8, and 15; Cycle 2, 4 and 8, Day 1 pre- and post-dose (each cycle is 21 days)
Safety Issue:
Description:
Measure:Pharmacokinetic Parameter Time to Maximum Plasma Concentration (Tmax) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a (Dose Escalation and Dose Expansion)
Time Frame:Dato-DXd, Cycle 1 and 3: Day 1 pre-dose, 30 minutes, 3 hours, 5 hours, 7 hours post-dose and Days 2, 4, 8, and 15; Cycle 2, 4 and 8, Day 1 pre- and post-dose (each cycle is 21 days)
Safety Issue:
Description:
Measure:Pharmacokinetic Parameter Area Under the Plasma Concentration-Time Curve (AUC) of Dato-DXd, Total anti-TROP2 antibody, and MAAA-1181a (Dose Escalation and Dose Expansion)
Time Frame:Dato-DXd, Cycle 1 and 3: Day 1 pre-dose, 30 minutes, 3 hours, 5 hours, 7 hours post-dose and Days 2, 4, 8, and 15; Cycle 2, 4 and 8, Day 1 pre- and post-dose (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)
Time Frame:Dato-DXd: Cycle 1 Day 1 and Day 8 and Cycle 2 Day 1; Durvalumab: Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 21 days)
Safety Issue:
Description:The immunogenicity of datopotamab deruxtecan (Dato-DXd) and durvalumab will be assessed.
Measure:Proportion of Participants Who Have Treatment-emergent ADA
Time Frame:Dato-DXd: Cycle 1 Day 1 and Day 8 and Cycle 2 Day 1; Durvalumab: Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 21 days)
Safety Issue:
Description:The immunogenicity of datopotamab deruxtecan (Dato-DXd) and durvalumab will be assessed.

Details

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

Trial Keywords

  • Advanced or Metastatic NSCLC
  • Datopotamab deruxtecan (Dato-DXd)
  • DS-1062a
  • Durvalumab

Last Updated

March 12, 2021