Clinical Trials /

DS-1062a in Combination With Pembrolizumab in Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung02)

NCT04526691

Description:

This study will assess safety and treatment activity of DS-1062a in combination with pembrolizumab in participants with advanced or metastatic 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 Pembrolizumab in Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-Lung02)
  • Official Title: Phase 1b, Multicenter, 2-part, Open-label Study of DS-1062a in Combination With Pembrolizumab 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-Lung02)

Clinical Trial IDs

  • ORG STUDY ID: DS1062-A-U102
  • SECONDARY ID: KEYNOTE KN-B43
  • NCT ID: NCT04526691

Conditions

  • Advanced or Metastatic NSCLC

Interventions

DrugSynonymsArms
DS-1062aDS-1062a
PembrolizumabDS-1062a

Purpose

This study will assess safety and treatment activity of DS-1062a in combination with pembrolizumab in participants with advanced or metastatic 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 and treatment activity of DS-1062a in combination with
      pembrolizumab 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 documents 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 pembrolizumab 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
  • Pembrolizumab

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 TPS 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 AE with prior treatment of anti-PD-1,
             anti-PD-L1, or anti programmed cell death ligand 2 (PD L2) agent or with an agent
             directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40,
             CD137).

          -  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 organ transplantation, including allogeneic tissue or solid organ
             transplantation.

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

Secondary Outcome Measures

Measure:Objective Response Rate (Dose Escalation and Dose Expansion)
Time Frame:Baseline up to BOR (confirmed CR or PR), 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 CR or PR) to PD or death (whichever occurs first), up to approximately 24 months postdose
Safety Issue:
Description:
Measure:Progression-free Survival (Dose Escalation and Dose Expansion)
Time Frame:Baseline up PD or death (whichever occurs first), 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:Cycle 1, Day 1: predose, 30 minutes, 3 hours (h), 5 h, and 7 h postdose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: predose 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:Cycle 1, Day 1: predose, 30 minutes, 3 hours (h), 5 h, and 7 h postdose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: predose 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:Cycle 1, Day 1: predose, 30 minutes, 3 hours (h), 5 h, and 7 h postdose; Cycles 1 and 3, Day 2, Day 4, Day 8, and Day 15; Cycles 2-4, Cycle 6, and Cycle 8, Day 1: predose 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.
Measure:Anti-drug Antibodies for DS-1062a and Pembrolizumab
Time Frame:Baseline up to approximately 24 months postdose
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Daiichi Sankyo, Inc.

Trial Keywords

  • Advanced or Metastatic NSCLC
  • DS-1062a
  • Pembrolizumab
  • KEYNOTE

Last Updated

August 24, 2020