Trial Outcomes & Findings for Open-Label Study of Parsaclisib, in Japanese Participants With Relapsed or Refractory Follicular Lymphoma (CITADEL-213) (NCT NCT04434937)

Last Updated: 2024-10-23

Results Overview

ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) as defined by revised response criteria for lymphoma, as determined by an Independent Review Committee (IRC). CR: target nodes/nodal masses regressed to ≤1.5 centimeters (cm) in the longest transverse diameter (LDi); no nonmeasured lesions; regression to normal for organ enlargement; no new lesions; and normal bone marrow by morphology and negative immunohistochemistry if indeterminate. PR: ≥50% decrease in sum of the product of the diameters (SPD) of up to 6 target measurable nodes and extranodal sites; absent/regressed nonmeasured lesions (but no increase); spleen regressed by \>50% in length beyond normal; and no new lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

up to approximately 3 years

Results posted on

2024-10-23

Participant Flow

This study was conducted at 19 study centers in Japan.

Participant milestones

Participant milestones
Measure	Parsaclisib 20 mg/2.5 mg Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.
Overall Study STARTED	42
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	42

Reasons for withdrawal

Reasons for withdrawal
Measure	Parsaclisib 20 mg/2.5 mg Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.
Overall Study Death	4
Overall Study Withdrawal by Subject	1
Overall Study Transitioned to Rollover Study	19
Overall Study Progressive Disease	18

Baseline Characteristics

Only participants with available data (who had measurable regions) were analyzed.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Parsaclisib 20 mg/2.5 mg n=42 Participants Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.
Age, Continuous	67.5 years STANDARD_DEVIATION 7.81 • n=42 Participants
Sex: Female, Male Female	20 Participants n=42 Participants
Sex: Female, Male Male	22 Participants n=42 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=42 Participants
Race (NIH/OMB) Asian	42 Participants n=42 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=42 Participants
Race (NIH/OMB) Black or African American	0 Participants n=42 Participants
Race (NIH/OMB) White	0 Participants n=42 Participants
Race (NIH/OMB) More than one race	0 Participants n=42 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=42 Participants
Target lesion size, as determined by Independent Review Committee and the Investigator Independent Review Committee	2210.12 millimeters squared (mm^2) STANDARD_DEVIATION 1456.044 • n=41 Participants • Only participants with available data (who had measurable regions) were analyzed.
Target lesion size, as determined by Independent Review Committee and the Investigator Investigator	2487.24 millimeters squared (mm^2) STANDARD_DEVIATION 2197.143 • n=42 Participants • Only participants with available data (who had measurable regions) were analyzed.

PRIMARY outcome

Timeframe: up to approximately 3 years

Population: Full Analysis Set: all participants enrolled in the study who received at least 1 dose of parsaclisib. Confidence intervals were calculated based on the exact method for binomial distributions.

Outcome measures

Outcome measures
Measure	Parsaclisib 20 mg/2.5 mg n=42 Participants Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.
Objective Response Rate (ORR)	88.1 percentage of participants Interval 74.4 to 96.0

SECONDARY outcome

Timeframe: up to approximately 3 years

Population: Full Analysis Set. Confidence intervals were calculated based on the exact method for binomial distributions.

CRR was defined as the percentage of participants with a CR as defined by revised response criteria for lymphoma, as determined by an IRC. CR was defined as: target nodes/nodal masses regressed to ≤1.5 cm in the LDi; no nonmeasured lesions; regression to normal for organ enlargement; no new lesions; and normal bone marrow by morphology and negative immunohistochemistry if indeterminate.

Outcome measures

Outcome measures
Measure	Parsaclisib 20 mg/2.5 mg n=42 Participants Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.
Complete Response Rate (CRR)	23.8 percentage of participants Interval 12.1 to 39.5

SECONDARY outcome

Timeframe: up to 20.0 months

Population: Full Analysis Set. Only participants with a CR or PR were analyzed. The 95% confidence interval was calculated using the generalization of Brookmeyer and Crowley's method with log-log transformation.

DOR was defined as the time from the first documented evidence of CR or PR until disease progression or death from any cause among participants who achieved an objective response, as determined by radiographic disease assessment provided by an IRC. Progressive disease was defined as ≥1 of the following: abnormal individual node/lesion meeting specific criteria; new/recurrent splenomegaly; new/clear progression of pre-existing nonmeasured lesions; regrowth of any previously resolved lesions; new node \>1.5 cm in any axis; new extranodal site \>1.0 cm in any axis; assessable disease of any size attributable to lymphoma; new/recurrent involvement of bone marrow.

Outcome measures

Outcome measures
Measure	Parsaclisib 20 mg/2.5 mg n=37 Participants Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.
Duration of Response (DOR)	NA months Interval 8.02 to The median and the upper limit of the confidence interval were not estimable because too few participants had disease progression or died.

SECONDARY outcome

Timeframe: up to approximately 3 years

Population: Fully Analysis Set. The 95% confidence interval was calculated using the generalization of Brookmeyer and Crowley's method with log-log transformation.

PFS was defined as the time from the date of the first dose of study treatment until the earliest date of disease progression, as determined by radiographic disease assessment provided by an IRC, or death from any cause. Progressive disease was defined as any new lesion or increase by ≥ 50% of previously involved sites from nadir.

Outcome measures

Outcome measures
Measure	Parsaclisib 20 mg/2.5 mg n=42 Participants Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.
Progression-free Survival (PFS)	NA months Interval 11.17 to The median and the upper limit of the confidence interval were not estimable because too few participants had disease progression or died.

SECONDARY outcome

Timeframe: up to approximately 3 years

Population: Full Analysis Set. The 95% confidence interval was calculated using the generalization of Brookmeyer and Crowley's method with log-log transformation.

Overall survival was defined as the time from the date of the first dose of study treatment until death from any cause.

Outcome measures

Outcome measures
Measure	Parsaclisib 20 mg/2.5 mg n=42 Participants Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.
Overall Survival	NA months Interval 23.06 to The median and the upper limit of the confidence interval were not estimable because too few participants died.

SECONDARY outcome

Timeframe: up to approximately 3 years

Population: Full Analysis Set. Only participants with available data (who had measurable regions) were analyzed.

Target lesion size was measured by the sum of the products of the diameters of all target lesion sizes. The best percent change from Baseline was defined as the largest decrease, or smallest increase if no decrease, from Baseline in target lesion sizes on/before new anti-lymphoma therapy during the study. Percentage change was calculated as (\[the post-Baseline value minus the Baseline value\] / the Baseline value) x 100.

Outcome measures

Outcome measures
Measure	Parsaclisib 20 mg/2.5 mg n=42 Participants Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.
Best Percentage Change in Target Lesion Size From Baseline, as Determined by Independent Review Committee and the Investigator Independent Review Committee	-67.26 percent change Standard Deviation 39.897
Best Percentage Change in Target Lesion Size From Baseline, as Determined by Independent Review Committee and the Investigator Investigator	-79.31 percent change Standard Deviation 23.181

SECONDARY outcome

Timeframe: up to 1041 days

Population: Safety Population: all enrolled participants who received at least 1 dose of parsaclisib

An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last administration of study drug.

Outcome measures

Outcome measures
Measure	Parsaclisib 20 mg/2.5 mg n=42 Participants Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	42 Participants

SECONDARY outcome

Timeframe: up to 1041 days

Population: Safety Population

An adverse event was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last administration of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.

Outcome measures

Outcome measures
Measure	Parsaclisib 20 mg/2.5 mg n=42 Participants Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.
Number of Participants With Any Grade 3 or Higher TEAE	28 Participants

Adverse Events

Parsaclisib 20 mg/2.5 mg

Serious events: 15 serious events

Other events: 38 other events

Deaths: 4 deaths

Total

Serious events: 15 serious events

Other events: 38 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

Incyte Corporation

Phone: 1-855-463-3463

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.
Publication restrictions are in place

Restriction type: OTHER

Measure	Parsaclisib 20 mg/2.5 mg n=42 participants at risk Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.	Total n=42 participants at risk Total
Vascular disorders Aortic aneurysm	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Musculoskeletal and connective tissue disorders Arthritis	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Cardiac disorders Atrial fibrillation	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Infections and infestations COVID-19	4.8% 2/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	4.8% 2/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Cardiac disorders Cardiac failure	4.8% 2/42 • Number of events 2 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	4.8% 2/42 • Number of events 2 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Eye disorders Cataract	2.4% 1/42 • Number of events 2 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 2 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Gastrointestinal disorders Cheilitis	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Infections and infestations Cytomegalovirus colitis	4.8% 2/42 • Number of events 2 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	4.8% 2/42 • Number of events 2 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Infections and infestations Cytomegalovirus enteritis	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Gastrointestinal disorders Diarrhoea	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Blood and lymphatic system disorders Febrile neutropenia	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Injury, poisoning and procedural complications Fracture	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Hepatobiliary disorders Hepatic function abnormal	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Gastrointestinal disorders Immune-mediated enterocolitis	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Cardiac disorders Myocardial infarction	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
General disorders Pyrexia	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Gastrointestinal disorders Stomatitis	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Infections and infestations Urethritis	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Infections and infestations Pyelonephritis acute	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	2.4% 1/42 • Number of events 1 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.

Measure	Parsaclisib 20 mg/2.5 mg n=42 participants at risk Participants received parsaclisib 20 milligrams (mg) once daily for 8 weeks, followed by 2.5 mg once daily, continuously. Participants received treatment until disease progression, death, hematopoietic stem cell transplantation (HSCT) (if eligible), unacceptable toxicity, or consent withdrawal.	Total n=42 participants at risk Total
Investigations Alanine aminotransferase increased	9.5% 4/42 • Number of events 6 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	9.5% 4/42 • Number of events 6 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Musculoskeletal and connective tissue disorders Arthralgia	11.9% 5/42 • Number of events 5 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	11.9% 5/42 • Number of events 5 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Investigations Aspartate aminotransferase increased	9.5% 4/42 • Number of events 6 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	9.5% 4/42 • Number of events 6 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Musculoskeletal and connective tissue disorders Back pain	9.5% 4/42 • Number of events 4 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	9.5% 4/42 • Number of events 4 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Infections and infestations Conjunctivitis	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Gastrointestinal disorders Constipation	19.0% 8/42 • Number of events 8 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	19.0% 8/42 • Number of events 8 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Infections and infestations Cytomegalovirus infection reactivation	14.3% 6/42 • Number of events 6 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	14.3% 6/42 • Number of events 6 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Metabolism and nutrition disorders Decreased appetite	9.5% 4/42 • Number of events 5 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	9.5% 4/42 • Number of events 5 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Metabolism and nutrition disorders Dehydration	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Gastrointestinal disorders Diarrhoea	26.2% 11/42 • Number of events 21 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	26.2% 11/42 • Number of events 21 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Skin and subcutaneous tissue disorders Dry skin	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Skin and subcutaneous tissue disorders Eczema	11.9% 5/42 • Number of events 6 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	11.9% 5/42 • Number of events 6 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Infections and infestations Herpes zoster	11.9% 5/42 • Number of events 5 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	11.9% 5/42 • Number of events 5 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Vascular disorders Hypertension	9.5% 4/42 • Number of events 4 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	9.5% 4/42 • Number of events 4 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Metabolism and nutrition disorders Hypoalbuminaemia	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Immune system disorders Hypogammaglobulinaemia	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Metabolism and nutrition disorders Hypokalaemia	9.5% 4/42 • Number of events 4 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	9.5% 4/42 • Number of events 4 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Gastrointestinal disorders Nausea	9.5% 4/42 • Number of events 5 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	9.5% 4/42 • Number of events 5 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Blood and lymphatic system disorders Neutropenia	11.9% 5/42 • Number of events 12 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	11.9% 5/42 • Number of events 12 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Investigations Neutrophil count decreased	21.4% 9/42 • Number of events 28 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	21.4% 9/42 • Number of events 28 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Skin and subcutaneous tissue disorders Pruritus	11.9% 5/42 • Number of events 5 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	11.9% 5/42 • Number of events 5 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
Gastrointestinal disorders Stomatitis	19.0% 8/42 • Number of events 11 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	19.0% 8/42 • Number of events 11 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
General disorders Oedema peripheral	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.
General disorders Pyrexia	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.	7.1% 3/42 • Number of events 3 • up to 1041 days Treatment-emergent adverse events (TEAE ), defined as any adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last administration of study drug, have been reported.