Trial Condition(s):

Carcinoma, Non-Small-Cell Lung

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

Bayer Identifier:

19781

ClinicalTrials.gov Identifier:

NCT03996473

EudraCT Number:

2018-003704-39

Recruitment Complete

Trial 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.

Inclusion Criteria
- Histologically or cytologically confirmed diagnosis of stage IV NSCLC. 
-- Phase 2 Cohort 1: No Epidermal Growth Factor Receptor (EGFR) / v-Raf murine sarcoma viral oncogene homolog B (BRAF) 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 inhibitor.  Prior treatment with platinum-based chemotherapy in combination or in sequence in line with local standard of care.
-- 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.

Trial Summary

Enrollment Goal
164
Trial Dates
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Phase
1
Could I receive a placebo?
No
Products
Radium-223 dichloride+pembrolizumab (BAY88-8223)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

UZ Gent

GENT, Belgium, 9000

Status
Completed
 
Locations

Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Barcelona, Spain, 08035

Status
Completed
 
Locations

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Status
Active, not recruiting
 
Locations

Hospital Clínic i Provincial de Barcelona

Barcelona, Spain, 08036

Status
Completed
 
Locations

Ccare San Marcos Cancer Center & Urology

San Marcos, United States, 92069

Status
Completed
 
Locations

Nederlands Kanker Instituut

AMSTERDAM, Netherlands, 1066 CX

Status
Completed
 

Trial Design