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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

Terminated Phase 1 Results posted Last updated 10 October 2024
What this trial tests

Phase 1 trial testing Radium-223 dichloride (Xofigo, BAY 88-8223) in Carcinoma, Non-Small-Cell Lung in 8 participants. Terminated before completion.

Timeline
6 March 2020
Primary endpoint
14 April 2021
30 January 2023

Quick facts

Lead sponsorBayer
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designsequential
Maskingnone
Primary purposetreatment
Enrollment8
Start date6 March 2020
Primary completion14 April 2021
Estimated completion30 January 2023
Sites6 locations across Belgium, Netherlands, United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Bayer — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Non-Small-Cell Lung. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-emergent Adverse Events in Phase 1 Primary · 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.

Any TEAE
GroupValue95% CI
Radium-223 Dichloride + Pembrolizumab7
Any TEAE - Maximum Grade 1
GroupValue95% CI
Radium-223 Dichloride + Pembrolizumab0
Any TEAE - Maximum Grade 2
GroupValue95% CI
Radium-223 Dichloride + Pembrolizumab3
Any TEAE - Maximum Grade 3
GroupValue95% CI
Radium-223 Dichloride + Pembrolizumab2
Any TEAE - Maximum Grade 4
GroupValue95% CI
Radium-223 Dichloride + Pembrolizumab0
Any TEAE - Maximum Grade 5
GroupValue95% CI
Radium-223 Dichloride + Pembrolizumab2
Number of Participants With Treatment-emergent Serious Adverse Events in Phase 1 Primary · 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 partici

GroupValue95% CI
Radium-223 Dichloride + Pembrolizumab2
Number of Participants With Dose Limiting Toxicities (DLTs) in Phase 1 Primary · 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 r

GroupValue95% CI
Radium-223 Dichloride + Pembrolizumab0
Number of Participants Categorized by Best Tumor Responses Per RECIST v1.1 in Phase 1 Secondary · Up to 188 days

The tumor responses were evaluated per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST V1.1).

GroupValue95% CI
Radium-223 Dichloride + Pembrolizumab1
Radium-223 Dichloride + Pembrolizumab5
Radium-223 Dichloride + Pembrolizumab1
Objective Response Rate (ORR) Per RECIST v1.1 in Phase 1 Secondary · 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 baselin

GroupValue95% CI
Radium-223 Dichloride + Pembrolizumab0
Disease Control Rate (DCR) Per RECIST v1.1 in Phase 1 Secondary · 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

GroupValue95% CI
Radium-223 Dichloride + Pembrolizumab1

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of study treatment to 90 days after cessation of study treatment or 30 days after last dose of study treatment (EoT visit) if subject started new anti-cancer therapy (whichever was earlier) for serious TEAEs; or until EoT visit for other TEAEs, with a maximum of 278 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Radium-223 + Pembrolizumab
Serious: 2/7 (29%)
Deaths: 6/7

Serious adverse events (4 terms)

ReactionSystemRadium-223 + Pembrolizumab
Acute kidney injuryRenal and urinary disorders
Bone painMusculoskeletal and connective tissue disorders
Rectal haemorrhageGastrointestinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (27 terms — click to expand)

ReactionSystemRadium-223 + Pembrolizumab
AstheniaGeneral disorders
NauseaGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
ConstipationGastrointestinal disorders
CoughRespiratory, thoracic and mediastinal disorders
Decreased appetiteMetabolism and nutrition disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
PyrexiaGeneral disorders
VomitingGastrointestinal disorders
Weight decreasedInvestigations
Abdominal painGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
BronchitisInfections and infestations
Chest painGeneral disorders
DiarrhoeaGastrointestinal disorders
DyspepsiaGastrointestinal disorders
DysphoniaRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
GastritisGastrointestinal disorders
HyponatraemiaMetabolism and nutrition disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
Oedema peripheralGeneral disorders
PainGeneral disorders
Productive coughRespiratory, thoracic and mediastinal disorders
Sputum discolouredRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Acute kidney injury, Bone pain, Rectal haemorrhage, Respiratory failure.

Data from ClinicalTrials.gov NCT03996473 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
    Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
  2. Combination therapy with immune checkpoint inhibitors (ICIs); a new frontier.
    Vafaei S, Zekiy AO, Khanamir RA, Zaman BA, et al · · 2022 · cited 190× · PMID 34980128 · DOI 10.1186/s12935-021-02407-8
  3. Recent Advances in the Treatment of Bone Metastases and Primary Bone Tumors: An Up-to-Date Review.
    Bădilă AE, Rădulescu DM, Niculescu AG, Grumezescu AM, et al · · 2021 · cited 62× · PMID 34439383 · DOI 10.3390/cancers13164229
  4. Immune Checkpoint Inhibitor Therapy for Bone Metastases: Specific Microenvironment and Current Situation.
    Liu C, Wang M, Xu C, Li B, et al · · 2021 · cited 42× · PMID 34877360 · DOI 10.1155/2021/8970173
  5. Recent advances and impending challenges for the radiopharmaceutical sciences in oncology.
    Lapi SE, Scott PJH, Scott AM, Windhorst AD, et al · · 2024 · cited 39× · PMID 38821098 · DOI 10.1016/s1470-2045(24)00030-5
  6. Developments in Combining Targeted Radionuclide Therapies and Immunotherapies for Cancer Treatment.
    Kerr CP, Grudzinski JJ, Nguyen TP, Hernandez R, et al · · 2022 · cited 24× · PMID 36678756 · DOI 10.3390/pharmaceutics15010128
  7. Combined Targeted Radiopharmaceutical Therapy and Immune Checkpoint Blockade: From Preclinical Advances to the Clinic.
    Bellavia MC, Patel RB, Anderson CJ. · · 2022 · cited 22× · PMID 36215570 · DOI 10.2967/jnumed.122.264373
  8. Radiopharmaceuticals heat anti-tumor immunity.
    Sun Q, Li J, Ding Z, Liu Z. · · 2023 · cited 20× · PMID 36632233 · DOI 10.7150/thno.79806

Verify or expand the search:

Other trials of Radium-223 dichloride (Xofigo, BAY 88-8223)

Trials testing the same drug.

Other recruiting trials for Carcinoma, Non-Small-Cell Lung

Currently open trials in the same condition.

Other Bayer trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03996473.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing