Clinical trial NCT03996473: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: NSCLC
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2019-06-24
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of the study was 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 had not received any systemic therapy for their advanced disease or had progressed on prior immunologic checkpoint blockade with antibodies against the programmed cell death protein-(ligand) 1 (PD-1/PD-L1). In this study researchers wanted to measure tumor shrinkage in response to treatment and how long that shrinkage lasted and gathered 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events in Phase 1
timeFrame: Up to 218 days
measure: Number of Participants With Treatment-emergent Serious Adverse Events in Phase 1
timeFrame: Up to 278 days
measure: Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1
timeFrame: Within 6 weeks after the first administration of pembrolizumab
measure: Objective Response Rate (ORR) Per RECIST v1.1 in Phase 2
timeFrame: 0 day as Phase 2 never started due to the early termination of the study
Secondary outcomes:
measure: Number of Participants Categorized by Best Tumor Responses Per RECIST v1.1 in Phase 1
timeFrame: Up to 188 days
measure: Objective Response Rate (ORR) Per RECIST v1.1 in Phase 1
timeFrame: Up to 188 days
measure: Duration of Response (DoR) Per RECIST v1.1 in Phase 1
timeFrame: Up to 188 days
measure: Disease Control Rate (DCR) Per RECIST v1.1 in Phase 1
timeFrame: Up to 188 days
measure: Duration of Response (DoR) Per RECIST v1.1 in Phase 2
timeFrame: 0 day as Phase 2 never started due to the early termination of the study
measure: Disease Control Rate (DCR) Per RECIST v1.1 in Phase 2
timeFrame: 0 day as Phase 2 never started due to the early termination of the study
measure: Progression Free Survival (PFS) Per RECIST v1.1 in Phase 2
timeFrame: 0 day as Phase 2 never started due to the early termination of the study
measure: Overall Survival (OS) in Phase 2
timeFrame: 0 day as Phase 2 never started due to the early termination of the study
measure: Number of Participants With Treatment-emergent Adverse Events in Phase 2
timeFrame: 0 day as Phase 2 never started due to the early termination of the study
measure: Number of Participants With Treatment-emergent Serious Adverse Events in Phase 2
timeFrame: 0 day as Phase 2 never started due to the early termination of the study
Other outcomes:
Locations:
city: San Marcos
country: United States
facility: Ccare San Marcos Cancer Center & Urology
state: California
city: Gent
country: Belgium
facility: UZ Gent
city: Amsterdam
country: Netherlands
facility: Nederlands Kanker Instituut
city: Barcelona
country: Spain
facility: Ciutat Sanitaria i Universitaria de la Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
Study officials:
References: