Trial Outcomes & Findings for Study Evaluating the Addition of Pembrolizumab to Radium-223 in mCRPC (NCT NCT03093428)

Last Updated: 2025-03-28

Results Overview

Differences in immune infiltrating cells (CD8+ T-cells and CD4+ T-cells) in bone biopsy specimens were compared from baseline to 8 weeks on study therapy between the treatment arms.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

45 participants

Primary outcome timeframe

2 months

Results posted on

2025-03-28

Participant Flow

Participants were enrolled and underwent bone biopsy prior to randomization.

Participant milestones

Participant milestones
Measure	Pembrolizumab Plus Radium-223 * Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose * Pembrolizumab will be administered intravenously every 3 weeks at a pre-determined dose Radium-223 will be halted after 3 doses. Once radiographic progressive disease occurs, the last 3 doses of radium will be given. Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death. Pembrolizumab: Pembrolizumab is a PD-1 inhibitor. Pembrolizumab binds to human PD-1 and blocks the interaction between PD1 and its ligands.	Radium-223 \- Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death.
Overall Study STARTED	31	14
Overall Study COMPLETED	12	8
Overall Study NOT COMPLETED	19	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab Plus Radium-223 * Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose * Pembrolizumab will be administered intravenously every 3 weeks at a pre-determined dose Radium-223 will be halted after 3 doses. Once radiographic progressive disease occurs, the last 3 doses of radium will be given. Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death. Pembrolizumab: Pembrolizumab is a PD-1 inhibitor. Pembrolizumab binds to human PD-1 and blocks the interaction between PD1 and its ligands.	Radium-223 \- Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death.
Overall Study Not eligible for treatment	2	1
Overall Study Progression	14	4
Overall Study Death	1	0
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Study Evaluating the Addition of Pembrolizumab to Radium-223 in mCRPC

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab Plus Radium-223 n=29 Participants * Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose * Pembrolizumab will be administered intravenously every 3 weeks at a pre-determined dose Radium-223 will be halted after 3 doses. Once radiographic progressive disease occurs, the last 3 doses of radium will be given. Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death. Pembrolizumab: Pembrolizumab is a PD-1 inhibitor. Pembrolizumab binds to human PD-1 and blocks the interaction between PD1 and its ligands.	Radium-223 n=13 Participants \- Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death.	Total n=42 Participants Total of all reporting groups
Age, Continuous	69 years n=5 Participants	71 years n=7 Participants	70 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	13 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants	12 Participants n=7 Participants	39 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Volume of bone metastases < 4 bone metastases	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Volume of bone metastases ≥ 4 bone metastases	25 Participants n=5 Participants	12 Participants n=7 Participants	37 Participants n=5 Participants
Alkaline phosphatase < 220U/L	21 Participants n=5 Participants	11 Participants n=7 Participants	32 Participants n=5 Participants
Alkaline phosphatase ≥ 220 U/L	8 Participants n=5 Participants	2 Participants n=7 Participants	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 months

Population: Participants who initiated at least one dose of study treatment and available bone biopsy data on baseline and 8-week on treatment.

Differences in immune infiltrating cells (CD8+ T-cells and CD4+ T-cells) in bone biopsy specimens were compared from baseline to 8 weeks on study therapy between the treatment arms.

Outcome measures

Outcome measures
Measure	Pembrolizumab Plus Radium-223 n=21 Participants * Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose * Pembrolizumab will be administered intravenously every 3 weeks at a pre-determined dose Radium-223 will be halted after 3 doses. Once radiographic progressive disease occurs, the last 3 doses of radium will be given. Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death. Pembrolizumab: Pembrolizumab is a PD-1 inhibitor. Pembrolizumab binds to human PD-1 and blocks the interaction between PD1 and its ligands.	Radium-223 n=5 Participants \- Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death.
Number of Participants With Increased Immune Cell Infiltration Across Arms CD4+ T-cell infiltration levels · Increase	7 Participants	2 Participants
Number of Participants With Increased Immune Cell Infiltration Across Arms CD4+ T-cell infiltration levels · No increase	14 Participants	3 Participants
Number of Participants With Increased Immune Cell Infiltration Across Arms CD8+ T-cell infiltration levels · Increase	3 Participants	1 Participants
Number of Participants With Increased Immune Cell Infiltration Across Arms CD8+ T-cell infiltration levels · No increase	18 Participants	4 Participants

SECONDARY outcome

Timeframe: Toxicity was assessed every cycle and up to 22.4 months.

Population: Participants who initiated at least one dose of study treatment

Adverse events were assessed using NCI CTCAE (version 4.0). Treatment related adverse events were those that were deemed as "Definitely", "Probably" and "Possibly" related to the study treatment.

Outcome measures

Outcome measures
Measure	Pembrolizumab Plus Radium-223 n=29 Participants * Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose * Pembrolizumab will be administered intravenously every 3 weeks at a pre-determined dose Radium-223 will be halted after 3 doses. Once radiographic progressive disease occurs, the last 3 doses of radium will be given. Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death. Pembrolizumab: Pembrolizumab is a PD-1 inhibitor. Pembrolizumab binds to human PD-1 and blocks the interaction between PD1 and its ligands.	Radium-223 n=13 Participants \- Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death.
Number of Participants With Grade 3 or Higher Treatment Related Adverse Events	13 Participants	5 Participants

SECONDARY outcome

Timeframe: Imaging was performed every 12 weeks and up to 25 months.

Population: Participants who initiated at least one dose of study treatment

Progression-free survival (PFS) is defined as the time from the first dose of study drug to the earlier of the first documentation of definitive disease progression by RECIST v 1.1 for soft tissue disease and PCWG2 guidelines for bone disease or death due to any cause, or censored at last imaging date. Per RECIST, progression is defined 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. For the bone per PCWG2 criteria, appearance of at least 2 new lesions within 12 weeks and confirmed by a second scan \>=6 weeks. Median PFS is estimated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Pembrolizumab Plus Radium-223 n=29 Participants * Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose * Pembrolizumab will be administered intravenously every 3 weeks at a pre-determined dose Radium-223 will be halted after 3 doses. Once radiographic progressive disease occurs, the last 3 doses of radium will be given. Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death. Pembrolizumab: Pembrolizumab is a PD-1 inhibitor. Pembrolizumab binds to human PD-1 and blocks the interaction between PD1 and its ligands.	Radium-223 n=13 Participants \- Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death.
Median Progression-Free Survival	6.1 Months Interval 2.7 to 10.8	5.7 Months Interval 2.6 to Not enough subjects had progression or died to estimate the upper confidence limit within follow-up to 25 months.

SECONDARY outcome

Timeframe: Participants were followed up for ~36 months.

Population: Participants who initiated at least one dose of study treatment

Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive. Median OS is estimated using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Pembrolizumab Plus Radium-223 n=29 Participants * Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose * Pembrolizumab will be administered intravenously every 3 weeks at a pre-determined dose Radium-223 will be halted after 3 doses. Once radiographic progressive disease occurs, the last 3 doses of radium will be given. Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death. Pembrolizumab: Pembrolizumab is a PD-1 inhibitor. Pembrolizumab binds to human PD-1 and blocks the interaction between PD1 and its ligands.	Radium-223 n=13 Participants \- Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death.
Median Overall Survival	16.9 Months Interval 12.7 to Not enough subjects died to estimate the upper confidence limit within follow-up to 30 months.	16.0 Months Interval 9.0 to Not enough subjects died to estimate the upper confidence limit within follow-up to 30 months.

Adverse Events

Pembrolizumab Plus Radium-223

Serious events: 9 serious events

Other events: 30 other events

Deaths: 15 deaths

Radium-223

Serious events: 3 serious events

Other events: 13 other events

Deaths: 7 deaths

Serious adverse events

Other adverse events

Additional Information

Atish Choudhury

Dana Farber Cancer Institute

Phone: 617-632-6328

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Pembrolizumab Plus Radium-223 n=31 participants at risk * Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose * Pembrolizumab will be administered intravenously every 3 weeks at a pre-determined dose Radium-223 will be halted after 3 doses. Once radiographic progressive disease occurs, the last 3 doses of radium will be given. Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death. Pembrolizumab: Pembrolizumab is a PD-1 inhibitor. Pembrolizumab binds to human PD-1 and blocks the interaction between PD1 and its ligands.	Radium-223 n=14 participants at risk \- Radium-223 will be administered intravenously every 4 weeks at a pre-determined dose Radium-223: Radium-223 is a calcium mimetic that hones in on bone metastases. It binds to new bone stroma and emits alpha particles, which induce double-stranded DNA breaks that result in tumor cell death.
Nervous system disorders Abducens nerve disorder	0.00% 0/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	7.1% 1/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Cardiac disorders Acute coronary syndrome	0.00% 0/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	7.1% 1/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Endocrine disorders Adrenal insufficiency	6.5% 2/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Blood and lymphatic system disorders Anemia	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Investigations Aspartate aminotransferase increased	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Musculoskeletal and connective tissue disorders Back pain	6.5% 2/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Metabolism and nutrition disorders Dehydration	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Gastrointestinal disorders Diarrhea	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
General disorders Fever	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Infections and infestations Lung infection	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Nervous system disorders Oculomotor nerve disorder	0.00% 0/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	7.1% 1/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
General disorders Pain	0.00% 0/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	7.1% 1/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Investigations Platelet count decreased	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Respiratory, thoracic and mediastinal disorders Pneumonitis	6.5% 2/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Renal and urinary disorders Renal calculi	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Infections and infestations Sepsis	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Nervous system disorders Stroke	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Infections and infestations Urinary tract infection	6.5% 2/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Renal and urinary disorders Urinary tract obstruction	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.
Investigations White blood cell decreased	3.2% 1/31 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.	0.00% 0/14 • AE was measured from baseline to end of treatment. Participants were on study up to 35 and 27months for combination and monotherapy arms, respectively. A serious adverse event is classified using physician's discretion. All adverse events resulting in death, life threatening events, significant disability, prolonged hospitalization, congenital abnormality/birth defect, or new cancer will be considered a serious adverse event.