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

July 22, 2024 updated by: Bayer

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 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
8

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Phase 1: Radium-223+Pembrolizumab
Participants received radium-223 dichloride at 55 kBq/kg every 6 weeks in combination with pembrolizumab every 3 weeks.
Drug: Radium-223 dichloride (Xofigo, BAY 88-8223)
55 kBq/kg, intravenous (IV) injection, every 6 weeks for up to 6 administrations
Drug: Pembrolizumab
200 mg, IV infusion, every 3 weeks for a maximum of up to 35 administrations
Experimental: Phase 2 Cohort 1: Radium-223+Pembrolizumab
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.
Drug: Radium-223 dichloride (Xofigo, BAY 88-8223)
55 kBq/kg, intravenous (IV) injection, every 6 weeks for up to 6 administrations
Drug: Pembrolizumab
200 mg, IV infusion, every 3 weeks for a maximum of up to 35 administrations
Active Comparator: Phase 2 Cohort 1: Pembrolizumab alone
Participants was planned to receive 200 mg pembrolizumab every 3 weeks.
Drug: Pembrolizumab
200 mg, IV infusion, every 3 weeks for a maximum of up to 35 administrations
Experimental: Phase 2 Cohort 2: Radium-223+Pembrolizumab
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.
Drug: Radium-223 dichloride (Xofigo, BAY 88-8223)
55 kBq/kg, intravenous (IV) injection, every 6 weeks for up to 6 administrations
Drug: Pembrolizumab
200 mg, IV infusion, every 3 weeks for a maximum of up to 35 administrations

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Treatment-emergent Adverse Events in Phase 1
Time Frame: Up to 218 days
A treatment-emergent adverse event (TEAE) was any untoward medical occurrence in a participant, whether or not related to the treatment, arising or worsening after start of study treatment administration until the end of treatment visit (EoT visit, i.e. 30 [+7] days after last dose of study treatment). Severities of the TEAEs are summarized overall and by the maximum grade experienced by the participants for any TEAEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0.
Up to 218 days
Number of Participants With Treatment-emergent Serious Adverse Events in Phase 1
Time Frame: Up to 278 days
A treatment-emergent serious adverse event (TESAE) was any untoward medical occurrence that resulting in death, initial or prolonged inpatient hospitalization, life-threatening, persistent disability/incapacity, congenital anomaly/birth defect, another medical important serious event as judged by the investigator arising or worsening after start of study treatment administration until 90 days after the cessation of study treatment for serious AE (regardless of causality) or until the end of treatment visit (EoT visit, i.e. 30 [+7] days after last dose of study treatment) visit if the participant initiated new anti-cancer therapy, whichever was earlier.
Up to 278 days
Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1
Time Frame: Within 6 weeks after the first administration of pembrolizumab
Any of following toxicities (exceptions as in protocol) during DLT window was considered a DLT if assessed by investigator to be possibly, probably or definitely related to study treatment: 1.Grade 4 non-hematologic toxicity. 2.Grade 4 hematologic toxicity ≥7 days. 3.Any non-hematologic AE (excl. lab) ≥Grade 3. 4.Any Grade 3 non-hematologic lab value if clinically significant medical intervention required, or the abnormality led to hospitalization, or the abnormality persisted for >1 week. 5.Grade 3 abnormality in AST, ALT, or bilirubin without liver metastases at screening; The abnormality results in a Drug-induced Liver Injury. 6.Febrile neutropenia Grade 3 or 4. 7.Prolonged delay (>2 weeks) in initiating Cycle 2 of pembrolizumab due to treatment-related toxicity 8.Any treatment-related toxicity that caused the participant to discontinue treatment during Cycle 1 or 2. 9.Missing >25% of pembrolizumab doses as a result of drug-related AE(s) during the first cycle. 10.Grade 5 toxicity.
Within 6 weeks after the first administration of pembrolizumab
Objective Response Rate (ORR) Per RECIST v1.1 in Phase 2
Time Frame: 0 day as Phase 2 never started due to the early termination of the study
ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) during the course of the study. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions.
0 day as Phase 2 never started due to the early termination of the study

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Participants Categorized by Best Tumor Responses Per RECIST v1.1 in Phase 1
Time Frame: Up to 188 days
The tumor responses were evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1).
Up to 188 days
Objective Response Rate (ORR) Per RECIST v1.1 in Phase 1
Time Frame: Up to 188 days
ORR was defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) during the course of the study. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions. Number of participants with best overall response of CR or PR before early termination of the study is reported in the table below while percentage of participants is auto-calculated by ClinicalTrials.gov database.
Up to 188 days
Duration of Response (DoR) Per RECIST v1.1 in Phase 1
Time Frame: Up to 188 days
DoR was 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. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions.
Up to 188 days
Disease Control Rate (DCR) Per RECIST v1.1 in Phase 1
Time Frame: Up to 188 days
DCR was defined as the percentage of participants with CR or PR, or SD for at least 6 weeks during the course of the study. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions. Stable Disease (SD): Steady state of disease. Number of participants with best overall response of CR or PR or SD is reported below while percentage of participants is auto-calculated by ClinicalTrials.gov database.
Up to 188 days
Duration of Response (DoR) Per RECIST v1.1 in Phase 2
Time Frame: 0 day as Phase 2 never started due to the early termination of the study
DoR was 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. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions.
0 day as Phase 2 never started due to the early termination of the study
Disease Control Rate (DCR) Per RECIST v1.1 in Phase 2
Time Frame: 0 day as Phase 2 never started due to the early termination of the study
DCR was defined as the percentage of participants with CR or PR, or SD for at least 6 weeks during the course of the study. It was evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1). Complete Response (CR): Disappearance of all clinical and radiological evidence of tumor (both target and non-target). Any pathological lymph nodes (whether target or non-target) must have a reduction in short axis to < 10mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum, no unequivocal progression of existing non target lesions and no appearance of new lesions. Stable Disease (SD): Steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, no unequivocal progression of existing non target lesions and no appearance of new lesions.
0 day as Phase 2 never started due to the early termination of the study
Progression Free Survival (PFS) Per RECIST v1.1 in Phase 2
Time Frame: 0 day as Phase 2 never started due to the early termination of the study
Progression free survival (PFS) was defined as the time from start of any study treatment to the date of earliest radiological progression per RECIST 1.1 or death due to any cause, whichever occurs first. Participants who were alive and without progression at the time of database cut-off would be censored at the date of the last evaluable tumor assessment. RECIST: Response Evaluation Criteria in Solid Tumors
0 day as Phase 2 never started due to the early termination of the study
Overall Survival (OS) in Phase 2
Time Frame: 0 day as Phase 2 never started due to the early termination of the study
Overall survival (OS) was defined as the time from start of any study treatment to the date of death due to any cause. Participants who were alive at the time of database cut-off would be censored at the last date known to be alive or the database cut-off date, whichever occurs first.
0 day as Phase 2 never started due to the early termination of the study
Number of Participants With Treatment-emergent Adverse Events in Phase 2
Time Frame: 0 day as Phase 2 never started due to the early termination of the study
An treatment-emergent adverse event (TEAE) was any untoward medical occurrence in a participant, whether or not related to the treatment, arising or worsening after start of study treatment administration until the end of treatment visit (EoT visit, i.e. 30 [+7] days after last dose of study treatment). Severities of the TEAEs are summarized overall and by the maximum grade experienced by the participants for any TEAEs according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v.5.0.
0 day as Phase 2 never started due to the early termination of the study
Number of Participants With Treatment-emergent Serious Adverse Events in Phase 2
Time Frame: 0 day as Phase 2 never started due to the early termination of the study
A treatment-emergent serious adverse event (TESAE) was any untoward medical occurrence that resulting in death, initial or prolonged inpatient hospitalization, life-threatening, persistent disability/incapacity, congenital anomaly/birth defect, another medical important serious event as judged by the investigator arising or worsening after start of study treatment administration until 90 days after the cessation of study treatment for serious AE (regardless of causality) or until the end of treatment visit (EoT visit, i.e. 30 [+7] days after last dose of study treatment) visit if the participant initiated new anti-cancer therapy, whichever was earlier.
0 day as Phase 2 never started due to the early termination of the study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bayer

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 6, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 14, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 30, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 21, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 21, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 24, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 10, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 22, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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