Clinical Trials /

Study to Test the Safety and How Radium-223 Dichloride an Alpha Particle-emitting Radioactive Agent Works in Combination With Pembrolizumab an Immune Checkpoint Inhibitor in Patients With Stage IV Non-small Cell Lung Cancer With Bone Metastases

NCT03996473

Description:

The purpose of the study is to determine the safety and test the efficacy of the combination of radium-223 dichloride and pembrolizumab in patients with stage IV non-small cell lung cancer (NSCLC) with bone metastases who either have not received any systemic therapy for their advanced disease or have progressed on prior immunologic checkpoint blockade with antibodies against the programmed cell death protein-(ligand) 1 (PD-1/PD-L1). In this study researchers want to measure tumor shrinkage in response to treatment and how long that shrinkage lasts and gather information on safety. Pembrolizumab is an immunologic checkpoint blocker that promotes an immune response against the tumor. Radium-223 dichloride is an alpha particle-emitting radioactive agent which kills cancer cells.

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Test the Safety and How Radium-223 Dichloride an Alpha Particle-emitting Radioactive Agent Works in Combination With Pembrolizumab an Immune Checkpoint Inhibitor in Patients With Stage IV Non-small Cell Lung Cancer With Bone Metastases
  • Official Title: An Open-label, Multicenter, Phase 1/2 Study of Radium-223 Dichloride in Combination With Pembrolizumab in Participants With Stage IV Non-small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: 19781
  • SECONDARY ID: 2018-003704-39
  • NCT ID: NCT03996473

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
Radium-223 dichloride (Xofigo, BAY 88-8223)Phase 1: Radium-223+Pembrolizumab
PembrolizumabPhase 1: Radium-223+Pembrolizumab

Purpose

The purpose of the study is to determine the safety and test the efficacy of the combination of radium-223 dichloride and pembrolizumab in patients with stage IV non-small cell lung cancer (NSCLC) with bone metastases who either have not received any systemic therapy for their advanced disease or have progressed on prior immunologic checkpoint blockade with antibodies against the programmed cell death protein-(ligand) 1 (PD-1/PD-L1). In this study researchers want to measure tumor shrinkage in response to treatment and how long that shrinkage lasts and gather information on safety. Pembrolizumab is an immunologic checkpoint blocker that promotes an immune response against the tumor. Radium-223 dichloride is an alpha particle-emitting radioactive agent which kills cancer cells.

Trial Arms

NameTypeDescriptionInterventions
Phase 1: Radium-223+PembrolizumabExperimentalParticipants will receive radium-223 dichloride every 6 weeks in combination with pembrolizumab every 3 weeks
  • Radium-223 dichloride (Xofigo, BAY 88-8223)
  • Pembrolizumab
Phase 2 Cohort 1: Radium-223+PembrolizumabExperimentalParticipants will receive radium-223 dichloride every 6 weeks in combination with pembrolizumab every 3 weeks
  • Radium-223 dichloride (Xofigo, BAY 88-8223)
  • Pembrolizumab
Phase 2 Cohort 1: Pembrolizumab aloneActive ComparatorParticipants will receive pembrolizumab every 3 weeks
  • Pembrolizumab
Phase 2 Cohort 2: Radium-223+PembrolizumabExperimentalParticipants will receive radium-223 dichloride every 6 weeks in combination with pembrolizumab every 3 weeks
  • Radium-223 dichloride (Xofigo, BAY 88-8223)
  • Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically or cytologically confirmed diagnosis of stage IV NSCLC. Phase 2 Cohort
             1: no Epidermal Growth Factor Receptor (EGFR) sensitization (activating) mutation or
             anaplastic lymphoma kinase (ALK)/ROS1 rearrangement. Treatment naïve (no prior
             systemic therapy) for their metastatic NSCLC. Phase 2 Cohort 2: progression on prior
             treatment with an immune checkpoint inhibitor. Phase 1 includes participants meeting
             either Cohort 1 or Cohort 2 criteria.

          -  Measurable disease per RECIST v1.1.

          -  At least 2 skeletal metastases.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.

          -  Adequate bone marrow and organ function.

          -  Participants must be on a bone health agent (BHA) treatment, such as bisphosphonates
             or denosumab treatment unless such treatment is contraindicated or not recommended per
             investigator's judgement.

        Exclusion Criteria:

          -  Previous or concurrent cancer within 3 years prior to enrollment.

          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
             an agent directed to another stimulatory or co-inhibitory T-cell receptor. Phase 2
             Cohort 2: was discontinued from that treatment due to a Grade 3 or higher
             immune-related AEs (irAEs).

          -  Known active central nervous system metastases and/or carcinomatous meningitis.
             Participants with previously treated brain metastases may participate provided they
             are radiologically stable, clinically stable, and without requirement of steroid
             treatment for at least 14 days prior to first dose of study treatment.

          -  Active autoimmune disease that has required systemic treatment in the past 2 years.

          -  History of (non-infectious) pneumonitis that required steroids or has current
             pneumonitis.

          -  Known history or presence of osteonecrosis of jaw.

          -  Ongoing infection >Grade 2 NCI-CTCAE v.5.0 requiring systemic therapy.

          -  Significant acute GI disorders with diarrhea as a major symptom e.g., Crohn's disease,
             malabsorption, or ≥ NCI-CTCAE v.5.0 Grade 2 diarrhea of any etiology.

          -  History of osteoporotic fracture.

          -  Prior treatment with radium-223 dichloride or any therapeutic radiopharmaceutical.

          -  Prior radiotherapy within 21 days of planned start of study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with adverse events (AEs) in Phase 1
Time Frame:Until 30 days after the last dose of the study intervention (up to 4 years)
Safety Issue:
Description:ORR is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) during the course of the study.

Secondary Outcome Measures

Measure:ORR per RECIST v1.1 in Phase 1
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:ORR per iRECIST in Phase 1
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Duration of response (DOR) per RECIST v1.1 in Phase 1
Time Frame:Up to 5 years
Safety Issue:
Description:DOR is defined as the time interval from the date of first response (CR or PR) to the date of disease progression or death, whichever comes first.
Measure:DOR per iRECIST in Phase 1
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Disease control rate (DCR) per RECIST v1.1 in Phase 1
Time Frame:Up to 5 years
Safety Issue:
Description:DCR is defined as the percentage of participants with CR or PR, or SD for at least 6 weeks during the course of the study.
Measure:DCR per iRECIST in Phase 1
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:ORR per iRECIST in Phase 2
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:DOR per RECIST v1.1 in Phase 2
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:DOR per iRECIST in Phase 2
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:DCR per RECIST v1.1 in Phase 2
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:DCR per iRECIST in Phase 2
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Progression free survival (PFS) per RECIST v1.1 in Phase 2
Time Frame:Up to 5 years
Safety Issue:
Description:PFS is defined as the time period until the date of radiological progression or death whichever occurs first.
Measure:PFS per iRECIST in Phase 2
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Overall survival (OS) in Phase 2
Time Frame:Up to 5 years
Safety Issue:
Description:OS is defined as the time period until the death due to any cause.
Measure:Number of participants with AE in Phase 2
Time Frame:Until 30 days after the last dose of the study intervention (up to 5 years)
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bayer

Trial Keywords

  • NSCLC

Last Updated

December 18, 2019