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

Status and phase: Terminated; Phase 1

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Pembrolizumab; Drug: Radium-223 dichloride (Xofigo, BAY 88-8223)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03996473

19781

2018-003704-39 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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8 participants in 4 patient groups

Phase 1: Radium-223+Pembrolizumab

Experimental group

Description:

Participants received radium-223 dichloride at 55 kBq/kg every 6 weeks in combination with pembrolizumab every 3 weeks.

Treatment:

Drug: Radium-223 dichloride (Xofigo, BAY 88-8223)

Drug: Pembrolizumab

Phase 2 Cohort 1: Radium-223+Pembrolizumab

Experimental group

Description:

Participants was planned to receive radium-223 dichloride at the maximum tolerated dose (MTD) to be determined in the Phase 1 part every 6 weeks in combination with 200 mg pembrolizumab every 3 weeks.

Treatment:

Drug: Radium-223 dichloride (Xofigo, BAY 88-8223)

Drug: Pembrolizumab

Phase 2 Cohort 1: Pembrolizumab alone

Active Comparator group

Description:

Participants was planned to receive 200 mg pembrolizumab every 3 weeks.

Treatment:

Drug: Pembrolizumab

Phase 2 Cohort 2: Radium-223+Pembrolizumab

Experimental group

Description:

Participants was planned to receive radium-223 dichloride at the MTD to be determined in the Phase 1 part every 6 weeks in combination with 200 mg pembrolizumab every 3 weeks.

Treatment:

Drug: Radium-223 dichloride (Xofigo, BAY 88-8223)

Drug: Pembrolizumab