Trial Outcomes & Findings for Denosumab + PD-1 in Subjects With Stage III/ IV Melanoma (NCT NCT03620019)
NCT ID: NCT03620019
Last Updated: 2024-08-12
Results Overview
The antitumor effect of denosumab alone (i.e., after two loading doses of denosumab are given on day 1 and day 8) in patients with unresectable stage III or distant metastatic Programmed death-1 or Programmed death ligand 1 (PD-1/PD-L1) inhibitor-naïve cutaneous melanoma (stage III/IV) will be assessed by performing translational research on peripheral blood samples collected at baseline and on day 21 of the study. The hypothesis is that denosumab treatment will prevent the destruction of autoreactive T cells within the thymus -and therefore will increase the influx of those T cells into the blood, termed recent thymic emigrants (RTE). RTE will be measured by multiparameter flow cytometric analysis of cluster of differentiation CD4+ and CD8+ RTE isolated from peripheral blood. Results will be expressed as the change in the number of cells/microliter of peripheral blood between the baseline and the day 21 time points.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
25 participants
Primary outcome timeframe
3 weeks after start of denosumab
Results posted on
2024-08-12
Participant Flow
Twenty-five subjects were enrolled in the study between 09/10/2018-05/31/2022 in 2 centers in the United States.
Participant milestones
| Measure |
Single Arm: Denosumab+ PD-1 Inhibitor
Subjects in this trial will be given denosumab every 4 weeks, starting on day 1 of study treatment. An additional loading dose of denosumab will be administered on day 8. Subjects who started Pembrolizumab (initiated 21 days after the first dose of denosumab is given) will continue to have it administered intravenously (IV) every 3 weeks. New subjects will receive Nivolumab administered intravenously (IV) every 4 weeks (initiated 21 days after the first dose of denosumab is given). Combination therapy will continue as long as subjects benefit from therapy for up to 1 year.
Denosumab: A dose of 120 mg will be administered as a subcutaneous (s.c.) injection every 4 weeks in the upper arm, upper thigh, or abdomen. Another loading dose of 120 mg s.c. denosumab will be administered on day 8. On days when denosumab is administered on the same day as pembrolizumab, the s.c. injection should be given after the infusion of pembrolizumab is completed.
Pembrolizumab: Pembrolizumab will be administered as standard of care following the institutional guidelines.The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over approximately 30 minutes (range: 25 - 40 minutes) every 3 weeks until disease progression or unacceptable toxicity.
Nivolumab: Nivolumab will be given every four weeks at a dose of 480 mg to be administered as an IV infusion per institutional guidelines.
|
|---|---|
|
Overall Study
STARTED
|
25
|
|
Overall Study
COMPLETED
|
25
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Denosumab + PD-1 in Subjects With Stage III/ IV Melanoma
Baseline characteristics by cohort
| Measure |
Single Arm: Denosumab+ PD-1 Inhibitor
n=25 Participants
Subjects in this trial will be given denosumab every 4 weeks, starting on day 1 of study treatment. An additional loading dose of denosumab will be administered on day 8. Subjects who started Pembrolizumab (initiated 21 days after the first dose of denosumab is given) will continue to have it administered intravenously (IV) every 3 weeks. New subjects will receive Nivolumab administered intravenously (IV) every 4 weeks (initiated 21 days after the first dose of denosumab is given). Combination therapy will continue as long as subjects benefit from therapy for up to 1 year.
Denosumab: A dose of 120 mg will be administered as a subcutaneous (s.c.) injection every 4 weeks in the upper arm, upper thigh, or abdomen. Another loading dose of 120 mg s.c. denosumab will be administered on day 8. On days when denosumab is administered on the same day as pembrolizumab, the s.c. injection should be given after the infusion of pembrolizumab is completed.
Pembrolizumab: Pembrolizumab will be administered as standard of care following the institutional guidelines.The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over approximately 30 minutes (range: 25 - 40 minutes) every 3 weeks until disease progression or unacceptable toxicity.
Nivolumab: Nivolumab will be given every four weeks at a dose of 480 mg to be administered as an IV infusion per institutional guidelines.
|
|---|---|
|
Age, Continuous
|
56.12 years
STANDARD_DEVIATION 12.48 • n=93 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
25 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 3 weeks after start of denosumabPopulation: Subjects received denosumab alone and provided blood sample at baseline and week 3.
The antitumor effect of denosumab alone (i.e., after two loading doses of denosumab are given on day 1 and day 8) in patients with unresectable stage III or distant metastatic Programmed death-1 or Programmed death ligand 1 (PD-1/PD-L1) inhibitor-naïve cutaneous melanoma (stage III/IV) will be assessed by performing translational research on peripheral blood samples collected at baseline and on day 21 of the study. The hypothesis is that denosumab treatment will prevent the destruction of autoreactive T cells within the thymus -and therefore will increase the influx of those T cells into the blood, termed recent thymic emigrants (RTE). RTE will be measured by multiparameter flow cytometric analysis of cluster of differentiation CD4+ and CD8+ RTE isolated from peripheral blood. Results will be expressed as the change in the number of cells/microliter of peripheral blood between the baseline and the day 21 time points.
Outcome measures
| Measure |
CD4+ Baseline
n=23 Participants
CD4+ values were determined from peripheral blood samples collected at baseline.
|
CD8+ Baseline
n=23 Participants
CD8+ values were determined from peripheral blood samples collected at baseline
|
CD4+ at 3 Weeks
n=23 Participants
CD4+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD8+ at 3 Weeks
n=23 Participants
CD8+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD4+ at Week 40
CD4+ values were determined from peripheral blood samples collected at week 40.
|
CD8+ at Week 40
CD8+ values were determined from peripheral blood samples collected at week 40
|
|---|---|---|---|---|---|---|
|
The Antitumor Effect of Denosumab Alone as Represented by the Change in Recent Thymic Emigrant Cells in Peripheral Blood
|
2.69 number of cell per microliter
Interval 0.34 to 15.9
|
2.42 number of cell per microliter
Interval 0.34 to 15.9
|
2.55 number of cell per microliter
Interval 0.32 to 12.0
|
1.92 number of cell per microliter
Interval 0.32 to 12.0
|
—
|
—
|
PRIMARY outcome
Timeframe: 3 weeks after start of denosumabPopulation: Subjects who started Denosumab alone study treatment, tumor-infiltrating Cluster of Differentiation (CD8+) Cells (TILs) in Tumor Tissue tests were performed at baseline and on day 21, were included. Although a biopsy was taken from all the subjects, tissue samples of 4 subjects were not included due to no presence of viable tumors or a necrotic tumor was present.
The antitumor effect of denosumab alone (i.e., after two loading doses of denosumab are given on day 1 and day 8) in patients with unresectable stage III or distant metastatic Programmed death-1 or Programmed death ligand 1 (PD-1/PD-L1) inhibitor-naïve cutaneous melanoma (stage III/IV) will be assessed by performing translational research on tumor biopsy samples collected at baseline and on day 21 of the study. The hypothesis is that denosumab alone will increase influx of tumor-infiltrating CD8+ cells (TIL). The density of TILs (number of cells by tumor surface area in mm2) in tumor tissues will be evaluated by Immunohistochemistry (IHC) and Immunofluorescence (IF) studies.
Outcome measures
| Measure |
CD4+ Baseline
n=20 Participants
CD4+ values were determined from peripheral blood samples collected at baseline.
|
CD8+ Baseline
CD8+ values were determined from peripheral blood samples collected at baseline
|
CD4+ at 3 Weeks
CD4+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD8+ at 3 Weeks
CD8+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD4+ at Week 40
CD4+ values were determined from peripheral blood samples collected at week 40.
|
CD8+ at Week 40
CD8+ values were determined from peripheral blood samples collected at week 40
|
|---|---|---|---|---|---|---|
|
The Antitumor Effect of Denosumab Alone as Represented by the Change in Density of Tumor-infiltrating Cluster of Differentiation (CD8+) Cells (TILs) in Tumor Tissue.
The number of subjects with TIL values decreased
|
9 Participants
|
—
|
—
|
—
|
—
|
—
|
|
The Antitumor Effect of Denosumab Alone as Represented by the Change in Density of Tumor-infiltrating Cluster of Differentiation (CD8+) Cells (TILs) in Tumor Tissue.
The number of subjects with TIL values stable
|
7 Participants
|
—
|
—
|
—
|
—
|
—
|
|
The Antitumor Effect of Denosumab Alone as Represented by the Change in Density of Tumor-infiltrating Cluster of Differentiation (CD8+) Cells (TILs) in Tumor Tissue.
The number of subjects with TIL values increased
|
4 Participants
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 16, 28 and 40 weeks after start of denosumabPopulation: Subjects received denosumab combined with anti-PD-1 inhibitor (Pembrolizumab or Nivolumab) and provided blood samples at weeks 16, 28, and 40.
The antitumor effect of denosumab combined with anti-PD-1 inhibitor (Pembrolizumab or Nivolumab) in patients with unresectable stage III or distant metastatic Programmed death-1 or Programmed death ligand 1 (PD-1/PD-L1) inhibitor-naïve cutaneous melanoma (stage III/IV) will be assessed by performing translational research on peripheral blood samples collected at weeks 16, 28 and 40 of the study. The hypothesis is that denosumab treatment will prevent the destruction of autoreactive T cells within the thymus -and therefore will increase the influx of those T cells into the blood, termed recent thymic emigrants (RTE). RTE will be measured by multiparameter flow cytometric analysis of cluster of differentiation (CD)8+ and CD 4+ RTE isolated from peripheral blood. Results will be expressed as the change in the number of cells/microliter of peripheral blood between the week 16, 28, and 40 time points.
Outcome measures
| Measure |
CD4+ Baseline
n=23 Participants
CD4+ values were determined from peripheral blood samples collected at baseline.
|
CD8+ Baseline
n=23 Participants
CD8+ values were determined from peripheral blood samples collected at baseline
|
CD4+ at 3 Weeks
n=15 Participants
CD4+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD8+ at 3 Weeks
n=15 Participants
CD8+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD4+ at Week 40
n=13 Participants
CD4+ values were determined from peripheral blood samples collected at week 40.
|
CD8+ at Week 40
n=13 Participants
CD8+ values were determined from peripheral blood samples collected at week 40
|
|---|---|---|---|---|---|---|
|
The Antitumor Effect of Denosumab Combined With Anti-PD-1 Inhibitor as Represented by the Change in Recent Thymic Emigrant Cells in Peripheral Blood - CD8+
|
2.06 valuenumber of cell per microliter
Interval 0.06 to 7.58
|
1.64 valuenumber of cell per microliter
Interval 0.06 to 7.58
|
2.84 valuenumber of cell per microliter
Interval 0.16 to 20.3
|
2.76 valuenumber of cell per microliter
Interval 0.16 to 20.03
|
2.27 valuenumber of cell per microliter
Interval 0.4 to 11.0
|
1.76 valuenumber of cell per microliter
Interval 0.4 to 11.0
|
PRIMARY outcome
Timeframe: Baseline, 16 weeks after start of denosumab combined with anti-PD-1 inhibitorPopulation: Subjects who started study treatment, Denosumab Combined With Anti-PD-1 Inhibitor, Tumor-infiltrating Cluster of Differentiation (CD8+) Cells (TILs) in Tumor Tissue tests were performed, at baseline and 16 weeks after the treatment were included. Biopsy on week 16 was not mandatory per protocol.
The antitumor effect of denosumab combined with anti-PD-1 inhibitor (Pembrolizumab or Nivolumab) in patients with unresectable stage III or distant metastatic Programmed death-1 or Programmed death ligand 1 (PD-1/PD-L1) inhibitor-naïve cutaneous melanoma (stage III/IV) will be assessed by performing translational research on tumor biopsy samples collected at baseline, on day 21, and week 16 of the study. The density of TILs (number of cells by tumor surface area in mm2) in tumor tissues will be evaluated by Immunohistochemistry (IHC) and Immunofluorescence (IF) studies.
Outcome measures
| Measure |
CD4+ Baseline
n=3 Participants
CD4+ values were determined from peripheral blood samples collected at baseline.
|
CD8+ Baseline
CD8+ values were determined from peripheral blood samples collected at baseline
|
CD4+ at 3 Weeks
CD4+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD8+ at 3 Weeks
CD8+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD4+ at Week 40
CD4+ values were determined from peripheral blood samples collected at week 40.
|
CD8+ at Week 40
CD8+ values were determined from peripheral blood samples collected at week 40
|
|---|---|---|---|---|---|---|
|
The Antitumor Effect of Denosumab Combined With Anti-PD-1 Inhibitor as Represented by the Change in Density of Tumor-infiltrating Cluster of Differentiation (CD8+) Cells (TILs) in Tumor Tissue.
The number of subjects with TIL value decreased between week 3 to week 17
|
0 Participants
|
—
|
—
|
—
|
—
|
—
|
|
The Antitumor Effect of Denosumab Combined With Anti-PD-1 Inhibitor as Represented by the Change in Density of Tumor-infiltrating Cluster of Differentiation (CD8+) Cells (TILs) in Tumor Tissue.
The number of subjects with TIL value increased between week 3 to week 17
|
3 Participants
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 30 days after treatment is discontinuedPopulation: Subjects received the study treatment and adverse events were assessed.
The safety of the denosumab- anti-PD-1 inhibitor (Pembrolizumab or Nivolumab) combination will be assessed by continuous toxicity monitoring focusing on the incidence of serious adverse events (SAEs) with toxicity boundary rules. The NCI Common Terminology Criteria for Adverse Events V5 is a descriptive terminology which will be used for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Outcome measures
| Measure |
CD4+ Baseline
n=25 Participants
CD4+ values were determined from peripheral blood samples collected at baseline.
|
CD8+ Baseline
CD8+ values were determined from peripheral blood samples collected at baseline
|
CD4+ at 3 Weeks
CD4+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD8+ at 3 Weeks
CD8+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD4+ at Week 40
CD4+ values were determined from peripheral blood samples collected at week 40.
|
CD8+ at Week 40
CD8+ values were determined from peripheral blood samples collected at week 40
|
|---|---|---|---|---|---|---|
|
Number of Participants With Treatment-related Serious Adverse Events of the Denosumab Alone Plus Its Combination With Nivolumab
Rash maculo-papular
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-related Serious Adverse Events of the Denosumab Alone Plus Its Combination With Nivolumab
Pneumonitis
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Number of Participants With Treatment-related Serious Adverse Events of the Denosumab Alone Plus Its Combination With Nivolumab
Colitis
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 16 weeks after start of treatmentPopulation: Subjects received the study treatment and tumor response were assessed.
Antitumor response to the denosumab- anti-PD-1 inhibitor (Pembrolizumab or Nivolumab) combination at 16 weeks in patients with unresectable stage III or distant metastatic PD-1/PD-L1 inhibitor-naïve cutaneous melanoma (AJCC stage III/IV) will be assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) which defines Complete Response (CR) as Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; and Overall Response Rate (ORR) = CR + PR/total number of subjects.
Outcome measures
| Measure |
CD4+ Baseline
n=17 Participants
CD4+ values were determined from peripheral blood samples collected at baseline.
|
CD8+ Baseline
CD8+ values were determined from peripheral blood samples collected at baseline
|
CD4+ at 3 Weeks
CD4+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD8+ at 3 Weeks
CD8+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD4+ at Week 40
CD4+ values were determined from peripheral blood samples collected at week 40.
|
CD8+ at Week 40
CD8+ values were determined from peripheral blood samples collected at week 40
|
|---|---|---|---|---|---|---|
|
Overall Response Rate
Complete Response
|
2 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Overall Response Rate
Partial Response
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Overall Response Rate
Stable
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Overall Response Rate
Progression
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 1 year from start of study treatmentPopulation: Subjects received the study treatment and were followed-up.
The Overall Survival rate at 1-year is defined as the proportion of subjects still alive from day 1 of study treatment until one year after initiating study treatment
Outcome measures
| Measure |
CD4+ Baseline
n=23 Participants
CD4+ values were determined from peripheral blood samples collected at baseline.
|
CD8+ Baseline
CD8+ values were determined from peripheral blood samples collected at baseline
|
CD4+ at 3 Weeks
CD4+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD8+ at 3 Weeks
CD8+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD4+ at Week 40
CD4+ values were determined from peripheral blood samples collected at week 40.
|
CD8+ at Week 40
CD8+ values were determined from peripheral blood samples collected at week 40
|
|---|---|---|---|---|---|---|
|
Overall Survival Rate
Alive
|
18 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Overall Survival Rate
Died
|
5 Participants
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 months from start of study treatmentPopulation: Subjects received the study treatment and tumor responses were assessed.
Progression Free survival rate at 6 months is defined as the proportion of subjects without a progression or death event measured from day 1 of treatment until 6 months after initiating study treatment. Progression events will be defined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Outcome measures
| Measure |
CD4+ Baseline
n=23 Participants
CD4+ values were determined from peripheral blood samples collected at baseline.
|
CD8+ Baseline
CD8+ values were determined from peripheral blood samples collected at baseline
|
CD4+ at 3 Weeks
CD4+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD8+ at 3 Weeks
CD8+ values were determined from peripheral blood samples collected at 3 weeks of the study.
|
CD4+ at Week 40
CD4+ values were determined from peripheral blood samples collected at week 40.
|
CD8+ at Week 40
CD8+ values were determined from peripheral blood samples collected at week 40
|
|---|---|---|---|---|---|---|
|
Progression Free Survival Rate
Progression
|
11 Participants
|
—
|
—
|
—
|
—
|
—
|
|
Progression Free Survival Rate
No progression
|
12 Participants
|
—
|
—
|
—
|
—
|
—
|
Adverse Events
Single Arm: Denosumab+ PD-1 Inhibitor
Serious events: 13 serious events
Other events: 25 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
Single Arm: Denosumab+ PD-1 Inhibitor
n=25 participants at risk
Subjects in this trial will be given denosumab every 4 weeks, starting on day 1 of study treatment. An additional loading dose of denosumab will be administered on day 8. Subjects who started Pembrolizumab (initiated 21 days after the first dose of denosumab is given) will continue to have it administered intravenously (IV) every 3 weeks. New subjects will receive Nivolumab administered intravenously (IV) every 4 weeks (initiated 21 days after the first dose of denosumab is given). Combination therapy will continue as long as subjects benefit from therapy for up to 1 year.
Denosumab: A dose of 120 mg will be administered as a subcutaneous (s.c.) injection every 4 weeks in the upper arm, upper thigh, or abdomen. Another loading dose of 120 mg s.c. denosumab will be administered on day 8. On days when denosumab is administered on the same day as pembrolizumab, the s.c. injection should be given after the infusion of pembrolizumab is completed.
Pembrolizumab: Pembrolizumab will be administered as standard of care following the institutional guidelines.The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over approximately 30 minutes (range: 25 - 40 minutes) every 3 weeks until disease progression or unacceptable toxicity.
Nivolumab: Nivolumab will be given every four weeks at a dose of 480 mg to be administered as an IV infusion per institutional guidelines.
|
|---|---|
|
Endocrine disorders
Endocrine disorders - Other, specify
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Colitis
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Diarrhea
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Lymphocyte count decreased
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Nervous system disorders
Syncope
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Nervous system disorders
Vasovagal reaction
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Renal and urinary disorders
Acute kidney injury
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Vascular disorders
Vascular disorders - Other, specify
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Vascular disorders
Hypotension
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
Other adverse events
| Measure |
Single Arm: Denosumab+ PD-1 Inhibitor
n=25 participants at risk
Subjects in this trial will be given denosumab every 4 weeks, starting on day 1 of study treatment. An additional loading dose of denosumab will be administered on day 8. Subjects who started Pembrolizumab (initiated 21 days after the first dose of denosumab is given) will continue to have it administered intravenously (IV) every 3 weeks. New subjects will receive Nivolumab administered intravenously (IV) every 4 weeks (initiated 21 days after the first dose of denosumab is given). Combination therapy will continue as long as subjects benefit from therapy for up to 1 year.
Denosumab: A dose of 120 mg will be administered as a subcutaneous (s.c.) injection every 4 weeks in the upper arm, upper thigh, or abdomen. Another loading dose of 120 mg s.c. denosumab will be administered on day 8. On days when denosumab is administered on the same day as pembrolizumab, the s.c. injection should be given after the infusion of pembrolizumab is completed.
Pembrolizumab: Pembrolizumab will be administered as standard of care following the institutional guidelines.The recommended dose of pembrolizumab is 200 mg administered as an IV infusion over approximately 30 minutes (range: 25 - 40 minutes) every 3 weeks until disease progression or unacceptable toxicity.
Nivolumab: Nivolumab will be given every four weeks at a dose of 480 mg to be administered as an IV infusion per institutional guidelines.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
24.0%
6/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Blood and lymphatic system disorders
Eosinophilia
|
16.0%
4/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Blood and lymphatic system disorders
Lymph node pain
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Cardiac disorders
Palpitations
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Cardiac disorders
Sinus tachycardia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Ear and labyrinth disorders
Ear pain
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Endocrine disorders
Endocrine disorders - Other, specify
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Endocrine disorders
Hyperthyroidism
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Endocrine disorders
Hypothyroidism
|
16.0%
4/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Endocrine disorders
Testosterone deficiency
|
20.0%
5/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Eye disorders
Blurred vision
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Eye disorders
Cataract
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Eye disorders
Dry eye
|
24.0%
6/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Eye disorders
Eye disorders - Other, specify
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Eye disorders
Floaters
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Eye disorders
Photophobia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Abdominal distension
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Abdominal pain
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Bloating
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Colitis
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Constipation
|
52.0%
13/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Diarrhea
|
56.0%
14/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Dry mouth
|
24.0%
6/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Dyspepsia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Enterocolitis
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Flatulence
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Gastrointestinal disorders - Other, specify
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Gingival pain
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Hemorrhoidal hemorrhage
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Hemorrhoids
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Lip pain
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Mucositis oral
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Nausea
|
36.0%
9/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Stomach pain
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Gastrointestinal disorders
Toothache
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Eye disorders
Vomiting
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
General disorders
Chills
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
General disorders
Edema limbs
|
20.0%
5/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
General disorders
Fatigue
|
80.0%
20/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
General disorders
Fever
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
General disorders
Flu like symptoms
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
General disorders
General disorders and administration site conditions - Other, specify
|
20.0%
5/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
General disorders
Injection site reaction
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
General disorders
Malaise
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
General disorders
Non-cardiac chest pain
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
General disorders
Pain
|
44.0%
11/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Immune system disorders
Allergic reaction
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Immune system disorders
Immune system disorders - Other, specify
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Infections and infestations
Bronchial infection
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Infections and infestations
Conjunctivitis
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Infections and infestations
Eye infection
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Infections and infestations
Laryngitis
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Infections and infestations
Papulopustular rash
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Infections and infestations
Sinusitis
|
16.0%
4/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Infections and infestations
Upper respiratory infection
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Infections and infestations
Vaginal infection
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Infections and infestations
Wound infection
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Injury, poisoning and procedural complications
Bruising
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Injury, poisoning and procedural complications
fall
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Injury, poisoning and procedural complications
fracture
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, specify
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Alkaline phosphatase increased
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Aspartate aminotransferase increased
|
24.0%
6/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Blood bicarbonate decreased
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Blood bilirubin increased
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Blood lactate dehydrogenase increased
|
16.0%
4/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Blood prolactin abnormal
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Creatinine increased
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Hemoglobin increased
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Investigations - Other, specify
|
16.0%
4/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Lipase increased
|
36.0%
9/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Lymphocyte count decreased
|
32.0%
8/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Neutrophil count decreased
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Platelet count decreased
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Serum amylase increased
|
16.0%
4/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Thyroid stimulating hormone increased
|
16.0%
4/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Weight gain
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
Weight loss
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Investigations
White blood cell decreased
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Anorexia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Dehydration
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
44.0%
11/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hyperphosphatemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
40.0%
10/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
44.0%
11/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
36.0%
9/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
36.0%
9/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
20.0%
5/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Buttock pain
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
16.0%
4/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Muscle cramp
|
24.0%
6/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness lower limb
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal and connective tissue disorder - Other, specify
|
20.0%
5/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
16.0%
4/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
16.0%
4/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
48.0%
12/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic syndrome
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify
|
20.0%
5/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor hemorrhage
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain
|
28.0%
7/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Nervous system disorders
Dizziness
|
24.0%
6/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Nervous system disorders
Dysgeusia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Nervous system disorders
Extrapyramidal disorder
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Nervous system disorders
Headache
|
44.0%
11/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Nervous system disorders
Nervous system disorders - Other, specify
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Nervous system disorders
Neuralgia
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Nervous system disorders
Paresthesia
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Nervous system disorders
Somnolence
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Psychiatric disorders
Agitation
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Psychiatric disorders
Anxiety
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Psychiatric disorders
Confusion
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Psychiatric disorders
Depression
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Psychiatric disorders
Insomnia
|
32.0%
8/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Psychiatric disorders
Psychiatric disorders - Other, specify
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Psychiatric disorders
Restlessness
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Renal and urinary disorders
Glucosuria
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Renal and urinary disorders
Proteinuria
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Renal and urinary disorders
Renal and urinary disorders - Other, specify
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Renal and urinary disorders
Renal calculi
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Renal and urinary disorders
Urinary frequency
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Renal and urinary disorders
Urinary urgency
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Reproductive system and breast disorders
Irregular menstruation
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
32.0%
8/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
24.0%
6/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
20.0%
5/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus pain
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
8.0%
2/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Skin and subcutaneous tissue disorders
Nail changes
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
48.0%
12/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Skin and subcutaneous tissue disorders
Purpura
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
12.0%
3/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
56.0%
14/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
44.0%
11/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Skin and subcutaneous tissue disorders
Skin hypopigmentation
|
16.0%
4/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Surgical and medical procedures
Surgical and medical procedures - Other, specify
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Vascular disorders
Hypertension
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Vascular disorders
Lymphedema
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Vascular disorders
Phlebitis
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
|
Vascular disorders
Thromboembolic event
|
4.0%
1/25 • Up to 56 weeks
Adverse events were collected from day one of the study drug administration to 30 days after completion of treatment. Any hospital admission was graded as a serious adverse event per protocol.
|
Additional Information
Melahat Canter
University of North Carolina Lineberger Comprehensive Cancer Center
Phone: (919) 962-0000
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place