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

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

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.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Radium-223 dichloride (Xofigo, BAY 88-8223); Drug: Pembrolizumab

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Nederlands Kanker Instituut
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial de Barcelona
  • Barcelona, Spain, 08035
    • Ciutat Sanitaria i Universitaria de la Vall d'Hebron
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
• United States
  • California
    • San Marcos, California, United States, 92069
      • Ccare San Marcos Cancer Center & Urology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Radium-223+Pembrolizumab; Participants will receive radium-223 dichloride every 6 weeks in combination with pembrolizumab every 3 weeks	Drug: Radium-223 dichloride (Xofigo, BAY 88-8223); Intravenous (IV) injection, every 6 weeks for up to 6 administrations; Drug: Pembrolizumab; IV infusion, every 3 weeks for a maximum of up to 35 administrations
Experimental: Phase 2 Cohort 1: Radium-223+Pembrolizumab; Participants will receive radium-223 dichloride every 6 weeks in combination with pembrolizumab every 3 weeks	Drug: Radium-223 dichloride (Xofigo, BAY 88-8223); Intravenous (IV) injection, every 6 weeks for up to 6 administrations; Drug: Pembrolizumab; IV infusion, every 3 weeks for a maximum of up to 35 administrations
Active Comparator: Phase 2 Cohort 1: Pembrolizumab alone; Participants will receive pembrolizumab every 3 weeks	Drug: Pembrolizumab; IV infusion, every 3 weeks for a maximum of up to 35 administrations
Experimental: Phase 2 Cohort 2: Radium-223+Pembrolizumab; Participants will receive radium-223 dichloride every 6 weeks in combination with pembrolizumab every 3 weeks	Drug: Radium-223 dichloride (Xofigo, BAY 88-8223); Intravenous (IV) injection, every 6 weeks for up to 6 administrations; Drug: Pembrolizumab; IV infusion, every 3 weeks for a maximum of up to 35 administrations

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
Number of participants with dose limiting toxicities (DLTs) in Phase 1		Up to 6 weeks
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR per RECIST v1.1 in Phase 1		Up to 5 years
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
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
DoR per RECIST v1.1 in Phase 2		Up to 5 years
DCR per RECIST v1.1 in Phase 2		Up to 5 years
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
Overall survival (OS) in Phase 2	OS is defined as the time period until the death due to any cause.	Up to 5 years
Number of participants with AE in Phase 2		Until 30 days after the last dose of the study intervention (up to 5 years)

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2020
• Primary Completion (Actual): April 14, 2021
• Study Completion (Actual): January 30, 2023

Study Registration Dates

• First Submitted: June 21, 2019
• First Submitted That Met QC Criteria: June 21, 2019
• First Posted (Actual): June 24, 2019

Study Record Updates

• Last Update Posted (Estimate): March 6, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab; Radium Ra 223 dichloride
• Other Study ID Numbers: 19781; 2018-003704-39 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No