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

Carcinoma, Non-Small-Cell Lung Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT03996473
• Other study ID #: 19781
• Secondary ID: 2018-003704-39
• Status: Terminated
• Phase: Phase 1
• Start date: March 6, 2020
• Est. completion date: January 30, 2023

Study information

• Verified date: March 2023
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: January 30, 2023
• Est. primary completion date: April 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Radium-223 dichloride (Xofigo, BAY 88-8223)
Intravenous (IV) injection, every 6 weeks for up to 6 administrations
• Pembrolizumab
IV infusion, every 3 weeks for a maximum of up to 35 administrations

Locations

Country	Name	City	State
Belgium	UZ Gent	Gent
Netherlands	Nederlands Kanker Instituut	Amsterdam
Spain	Ciutat Sanitaria i Universitaria de la Vall d'Hebron	Barcelona
Spain	Hospital Clínic i Provincial de Barcelona	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
United States	Ccare San Marcos Cancer Center & Urology	San Marcos	California

Sponsors (2)

Lead Sponsor	Collaborator
Bayer	Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Belgium,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with adverse events (AEs) in Phase 1		Until 30 days after the last dose of the study intervention (up to 3 years)
Primary	Number of participants with dose limiting toxicities (DLTs) in Phase 1		Up to 6 weeks
Primary	Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 in Phase 2	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.	Up to 36 weeks
Secondary	ORR per RECIST v1.1 in Phase 1		Up to 5 years
Secondary	Duration of response (DoR) per RECIST v1.1 in Phase 1	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.	Up to 5 years
Secondary	Disease control rate (DCR) per RECIST v1.1 in Phase 1	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.	Up to 5 years
Secondary	DoR per RECIST v1.1 in Phase 2		Up to 5 years
Secondary	DCR per RECIST v1.1 in Phase 2		Up to 5 years
Secondary	Progression free survival (PFS) per RECIST v1.1 in Phase 2	PFS is defined as the time period until the date of radiological progression or death whichever occurs first.	Up to 5 years
Secondary	Overall survival (OS) in Phase 2	OS is defined as the time period until the death due to any cause.	Up to 5 years
Secondary	Number of participants with AE in Phase 2		Until 30 days after the last dose of the study intervention (up to 5 years)